Document of The World Bank FOR OFFICIAL USE ONLY Report No: ICR00004605 IMPLEMENTATION COMPLETION AND RESULTS REPORT ON A SMALL GRANT IN THE AMOUNT OF USD 3,593,757 TO THE International AIDS Vaccine Initiative FOR Support to Research and Development at the International AIDS Vaccine Initiative (P161232) April 5, 2019 Health, Nutrition & Population Global Practice Other Region Regional Vice President: Annette Dixon Country Director: Fadia M. Saadah Senior Global Practice Director: Timothy Grant Evans Practice Manager: E. Gail Richardson Task Team Leader(s): Robert Oelrichs ICR Main Contributor: Sara Halstead Hersey ABBREVIATIONS AND ACRONYMS AIDS Acquired Immune Deficiency Syndrome ART Antiretroviral therapy CEPI Coalition for Epidemic Preparedness Innovations CIA Comparative Infectivity Assay DCF Discounted Cash Flow DGF Development Grant Finance EMP Environmental Management Plan Gag Gene coding for the HIV Gag protein GHIT Fund Global Health Innovation Technology Fund GPG Global Public Good HIV Human Immunodeficiency Virus IAVI The International AIDS Vaccine Initiative IDA International Development Association IO Intermediate Outcome ISR Implementation Status Report LMIC Low and Middle Income Countries M&E Monitoring and Evaluation NHP Non-Human Primates NIH National Institutes of Health (e)NPV (expected) Net Present Value ODA Official Development Assistance PAD Project Appraisal Document PDO Project Development Objective PEF Pandemic Emergency Financing Facility PPSD Project Procurement Strategy for Development R&D Research and Development SeV Sendai Vector SHIV Simian/human Immunodeficiency Virus SOP Standard Operating Procedures TF Trust Fund TTL Task Team Leader UNAIDS Joint United Nations Programme on HIV/AIDS UHC Universal Health Coverage UNICEF United Nations International Children’s Emergency Fund USAID United States Agency for International Development VSV Vesicular Stomatitis Virus WHO World Health Organization TABLE OF CONTENTS DATA SHEET ....................................................................... ERROR! BOOKMARK NOT DEFINED. I. PROJECT CONTEXT AND DEVELOPMENT OBJECTIVES ....................................................... 4 II. OUTCOME ...................................................................................................................... 6 III. KEY FACTORS THAT AFFECTED IMPLEMENTATION AND OUTCOME ................................ 10 IV. BANK PERFORMANCE, COMPLIANCE ISSUES, AND RISK TO DEVELOPMENT OUTCOME .. 11 V. LESSONS LEARNED AND RECOMMENDATIONS .............................................................. 13 ANNEX 1. RESULTS FRAMEWORK AND KEY OUTPUTS ........................................................... 16 ANNEX 2. PROJECT COST BY COMPONENT ........................................................................... 25 ANNEX 3. RECIPIENT, CO-FINANCIER AND OTHER PARTNER/STAKEHOLDER COMMENTS ...... 26 ANNEX 4. LIST OF DOCUMENTS REVIEWED .......................................................................... 29 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) DATA SHEET BASIC INFORMATION Product Information Project ID Project Name Support to Research and Development at the P161232 International AIDS Vaccine Initiative Country Financing Instrument World Investment Project Financing Original EA Category Revised EA Category Partial Assessment (B) Partial Assessment (B) Organizations Borrower Implementing Agency International AIDS Vaccine Initiative International AIDS Vaccine Initiative Project Development Objective (PDO) Original PDO The Project Development Objective is to support the International AIDS Vaccine Initiative (IAVI) in the optimization and testing of one HIV vaccine candidate. Page 1 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) FINANCING FINANCE_TBL Original Amount (US$) Revised Amount (US$) Actual Disbursed (US$) Donor Financing TF-A4434 3,593,757 3,593,757 3,593,757 Total 3,593,757 3,593,757 3,593,757 Total Project Cost 3,593,757 3,593,757 3,593,757 KEY DATES Approval Effectiveness Original Closing Actual Closing 10-Feb-2017 27-Feb-2017 30-Jun-2017 30-Sep-2018 RESTRUCTURING AND/OR ADDITIONAL FINANCING Date(s) Amount Disbursed (US$M) Key Revisions 28-Sep-2017 1.80 Additional Financing Change in Results Framework Change in Components and Cost Change in Loan Closing Date(s) Change in Procurement Change in Implementation Schedule KEY RATINGS Outcome Bank Performance M&E Quality Highly Satisfactory Highly Satisfactory Substantial RATINGS OF PROJECT PERFORMANCE IN ISRs Actual No. Date ISR Archived DO Rating IP Rating Disbursements (US$M) 01 30-May-2017 Moderately Satisfactory Moderately Satisfactory 1.80 02 15-Nov-2017 Satisfactory Satisfactory 1.80 Page 2 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) 03 26-Sep-2018 Satisfactory Satisfactory 2.70 ADM STAFF Role At Approval At ICR Regional Vice President: Keith E. Hansen Annette Dixon Country Director: Olusoji O. Adeyi Fadia M. Saadah Senior Global Practice Director: Timothy Grant Evans Timothy Grant Evans Practice Manager: Ernest E. Massiah E. Gail Richardson Task Team Leader(s): Robert Oelrichs Robert Oelrichs ICR Contributing Author: Sara Halstead Hersey Page 3 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) I. PROJECT CONTEXT AND DEVELOPMENT OBJECTIVES Context At the time this operation was prepared, the need for a vaccine against Human Immunodeficiency Virus (HIV) remained urgent, with the epidemic contributing to reversals in health, food security, education and other measures of prosperity and stability. Approximately 5,753 people become newly infected with HIV each day. The pandemic is still outpacing current treatment and prevention efforts in many countries. There is no cure for HIV infection. However, effective antiretroviral medicines can control the virus and help prevent transmission so that people with HIV, and those at substantial risk, can enjoy healthy and productive lives. Another hope is that a vaccine can be developed against the virus, and its introduction will improve millions of lives around the world. Even though no vaccination is 100% effective, overall, immunization has proved to be one of the most cost-effective means to prevent vaccine-preventable diseases. A high public health value of a vaccine and projected savings of approximately US$1.5 billion per year by 2070 justify current investments into vaccine research and development (R&D). A 70% efficacious and well-adopted vaccine as part of a comprehensive HIV/AIDS response could prevent the majority of annual new infections. A vaccine’s impact would be even stronger should the funding and implementation of existing prevention and treatment programs fail to increase to the aspired levels. An HIV vaccine would contribute to 16.2 million fewer HIV infections by 2070 should prevention and treatment programs be significantly scaled-up globally and would reduce the number of new HIV infections by 42.8 million if prevention programs remain stagnant over the same time period. (IAVI Policy Brief. 2016) The International AIDS Vaccine Initiative (IAVI) was founded in 1996 with a global mandate to “ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world.� The World Bank was a founding partner of IAVI. Between 1996 and 2010, IAVI and its partners had achieved a series of ‘firsts’ to reshape the landscape of AIDS vaccine R&D. These included: (1) Development and testing of the first vaccine candidates based on HIV subtypes circulating in Africa and India; (2) Conducting the first AIDS vaccine trials in Kenya, Rwanda, Zambia and India; (3) Establishing the first laboratory accredited for assessing immune responses against HIV from vaccine trials; (4) Identifying the first potent and broadly neutralizing antibodies against HIV in more than a decade, which provided new targets on HIV for vaccine design; (5) Establishing the world's first Vaccine Design and Development Laboratory dedicated solely to the development of a safe and effective AIDS vaccine; and (6) Successfully advancing seven novel vaccine candidates from concept to clinical trials. IAVI was one of the first examples of Product Development Partnerships (PDP). The PDP's mission is to accelerate the translation of R&D from the bench to the bedside while supporting affordability and access to data. In a previous project supported by the World Bank (P119051), IAVI successfully constructed vaccine candidates using Sendai Vector (SeV), and the final ICR rated the project as highly successful. In this project, IAVI expanded upon previous work conducted with the support of the World Bank and other financing organizations in order to advance a live-virus HIV vaccine, in which a heterologous virus is engineered to expresses HIV antigen(s), with the aim of inducing a safe and protective immune response. This project was funded through a partnership between the Government of Japan and the World Bank under a hybrid Bank and Recipient- executed Trustee-level trust fund (TF-A4434). The small Bank-executed portion financed under this hybrid supported only World Bank supervision activities, including the consultancies of specialist, independent experts in this complex technical and product development area. The project became effective in February 2017 and retroactively financed activities that had begun in August 2016. This project was initially designed to be completed by June 2017 with a total budget of US$1.8 million. Page 4 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) In October 2017, the project was restructured and extended by 15 months to implement Additional Financing in the amount of US$1.79 million, retroactive from June 2017 through September 2018. While the Project Development Objective (PDO) remained the same, at this time two outcome indicators and four components were added to extend the scope of the vaccine development and optimization activities. (see below) Project Development Objectives (PDOs) The PDO was to support the International AIDS Vaccine Initiative (IAVI) in the optimization and testing of one HIV vaccine candidate. Key Expected Outcomes and Outcome Indicators The original Project Appraisal Document (PAD) included two outcome indicators and two additional outcome indicators were added during restructuring. Original outcomes 1. Vector has been optimized 2. Vector testing has been initiated Additional outcomes (at restructuring) 3. VSVdG-Env. BG505.1 vaccine vector has been evaluated 4. Additional viral vectors have been developed The PAD included 5 intermediate outcome (IO) indicators and 9 additional IOs were added during the restructuring. (see Annex 1.) Components There were two components included in the original project design, and four components were added during restructuring. The budget and expenditure for each component is included in Annex 2. Original components 1. Vector Optimization. Five new recombinant vaccines will be generated, their specificity will be tested along with vaccine strain prototype VSVdG-Env. BG505 2. Vector Testing. Production of two vaccine candidates and a launch of a comparative vaccine study in India rhesus macaques to analyze safety, immunogenicity, and efficacy. Additional components (at restructuring) 3. Comprehensive evaluation of VSVdG-Env. BG505.1 vaccine vector. Production of a vaccine seed. 4. Develop vectors with alternative strategic modifications designed to enhance the Env antibody response induced by VSV G-Env vaccines; Develop at least one additional vector for VSVdG virus vaccine (note: the component included the main component and a sub-component) 5. Develop a new Vero cell line that will support replication of VSV G-Env and produce virus particles bearing a VSV G glycoprotein pseudotype 6. Presentation of research in conferences and workshops Page 5 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) II. OUTCOME Relevance of objectives The relevance of the objectives of this project is high. Relevance PDO 1: Vector optimization High PDO 2: Vector testing High Overall rating High UNAIDS estimated approximately 2 million new HIV infections in the world in 2015. The 90-90-90 strategy (http://www.unaids.org/en/resources/documents/2014/90-90-90) may enhance early diagnosis with early treatment of HIV infected individuals, possibly reducing new infections. However, the development of an effective prophylactic HIV vaccine is crucial for global HIV control. Induction of effective antibodies broadly-reactive to highly-diversified HIVs by vaccines is believed to be a promising strategy for HIV prevention. The final goal of this project to develop a prophylactic HIV vaccine inducing effective anti-HIV antibodies remains highly relevant. The development of an HIV vaccine aligns with the development objectives of the Government of Japan and the World Bank. Objectives include 1) achieving progress on global public goods (GPGs), critical to global stability, poverty reduction, public health capacity and equitable growth; and 2) reducing the incidence of diseases of poverty. It aligns with the World Bank’s efforts to strengthen research and delivery systems for immunization. Investments in immunization are a critical component of Universal Health Coverage (UHC) and a strong force for poverty reduction. It also aligns with World Bank programs prioritizing capacity building in preventing, detecting and responding to infectious disease threats including the initiation of the World Bank Pandemic Emergency Financing Facility (PEF). This project, as well as the previous one with IAVI (P119051), also built on the World Bank’s financial oversight capabilities and the Bank’s convening power to bring different partners together and ensure technical oversight of this support. Efficacy in reaching objectives The efficacy in achieving the PDO is high. Efficacy PDO 1: Vector optimization High PDO 2: Vector testing High Overall rating High This project successfully and fully met targets for all PDO indicators, measured as binary ‘Yes/No’ in the results framework. Under the first PDO objective, vector has been optimized, IAVI successfully completed the three project outcomes and seven of the 11 intermediate results within the allotted timeframe. The intermediate results which were achieved are important for vaccine advancement including generating and testing vaccine variants, characterizing the stability and growth characteristics of the lead candidate, and establishing a second viral vector to mitigate the risk of anti-vector immunity. One of the intermediate results was partially achieved resulting Page 6 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) in an engineered cell line for scalable production of the desired lead candidate that was successfully tested for feasibility, though this still requires advancement to cell line development. Three intermediate indicators became non-relevant as the project progressed and did not impact the completion of the PDO. The intermediate results that were not achieved included further development of one variant which was stopped due to its inferior protection in a vaccine trial, and two ambitious aims to modify a VSV structural protein to reduce host innate anti-viral response were not advanced during the project timeline. A non-research component, presentation of research in conferences and workshops, was completed through the convening of a meeting on Japanese investments in global R&D. This activity supports both PDOs and has been included under PDO 1 for the purpose of this analysis. Under the second PDO objective, vector has been tested, IAVI successfully and fully completed the one project outcome and all three of the intermediate results within the allotted timeframe. The tables below aligns the outcomes, components and intermediate results for PDOs 1 and 2 and documents the efficacy of completion. A note that when intermediate results were not achieved it was because new data became available that informed the direction of research and the proposed activities were no longer considered relevant as discussed above. Activities were then adjusted accordingly based on discussion and agreement with the World Bank and subject matter experts. Project Development Objective 1: Vector has been optimized Project Components Intermediate results Outcomes/ Outcomes Intermediate results achieved (date assessed) PDO indicator 1: Vector has been optimized Yes (June 2017) Five new recombinant Five genetically modified VSVdG-Env.BG505 vaccines have vaccines will be generated, been isolated and characteristics have been analyzed Yes (June 2017) their specificity will be VSVdG-Env.BG505 mutants have been isolated after serial tested along with vaccine passage under conditions that select for viruses with strain prototype VSVdG- increased replicative fitness. Mutant virus characteristics Yes (June 2017) Env. BG505 have been analyzed. PDO indicator 2: VSVdG-Env. BG505.1 vaccine vector has been evaluated Yes (June 2018) Comprehensive evaluation Determination of construction feasibility and replicative of VSVdG-Env. BG505.1 capacity of VSVdG-Env.BG505 with Env in position 2, 3 or 5 vaccine vector. Production Yes (June 2018) of a vaccine seed. Initiate VSVdG-Env.BG505 position 1 vector vaccine rescue in Early Development Laboratory No (Sept 2018) PDO indicator 3: Additional viral vectors have been developed Yes (June 2018) Develop vectors with VSVdG-Env.BG505 position 1 vector with Matrix protein alternative strategic (M) modifications that will dampen the innate immune modifications designed to response rescued No (Sept 2018) enhance the Env antibody VSVdG-Env.BG505.1 vector with M modifications response induced by VSV evaluated for genetic stability and replicative capacity No (Sept 2018) G-Env vaccines; Develop at Conduct serial passage of VSV New Jersey vector to least one additional vector improve replicative capacity and fitness of the virus Yes (June 2018) Page 7 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) for VSVdG virus vaccine Evaluate VSV New Jersey vector for improved fitness and utility as a vaccine platform Yes (June 2018) Develop a new Vero cell Feasibility of VERO-CD4/CCR5 cell line also expressing VSV line that will support glycoprotein G is demonstrated Yes (June 2018) replication of VSV G-Env Initiate VERO CD4/CCR5 VSV G expressing cell line in Early and produce virus particles Development Laboratory No (Sept 2018) bearing a VSV G glycoprotein pseudotype Presentation of research in Organize and facilitate meeting in conjunction with UHC conferences and Forum in December in Tokyo on Japanese investments in Yes (June 2018) workshops global health R&D Project Development Objective 2: Vector has been tested PDO indicator 4: Vector testing has been initiated Yes (June 2017) Production of two vaccine A decision to test new VSVdG-Env.BG505 vaccines or revise candidates and a launch of a macaque study to evaluate the requirement for three a comparative vaccine doses have been made. Yes (June 2017) study in India rhesus Candidate vaccines have been produced for a preclinical macaques to analyze study. Yes (June 2017) safety, immunogenicity, Preclinical study in non-human primates has been and efficacy. commenced. Yes (June 2017) Efficiency in use of project funds The efficiency in the use of project funds is substantial. Efficiency PDO 1: Vector optimization Substantial PDO 2: Vector testing High Overall rating Substantial IAVI did a very strong job in the overall implementation of this project. In particular, IAVI met the timelines and objectives for the first phase of the project activities in generating new recombinant vaccines as part of vector optimization and in vector testing. The project delivered on all development objectives and fully disbursed all of its funding by the end of the project period without requiring any extensions. The initial costs projections and actual costs incurred were similar across budget categories indicating the initial planning was in-line with the ultimate project execution. Evaluating this operation’s efficiency according to traditional metrics is not straightforward. The expected net present value (eNPV) is a metric very often used in pharmaceutical development to value risky future cash flows. eNPV modifies the standard NPV calculation of discounted cash flow (DCF) analysis by adjusting each cash flow by the estimated probability that it occurs. This method is not be appropriate in this case given the uncertainty of the commercial model for an HIV vaccine, and it was not used by IAVI. However, this project contributed to eliminating technical risks inherent to vector construction, preclinical development, manufacturing process and clinical safety, hence significantly increasing the probability of bringing a virally vectored HIV vaccine to the market and the corresponding eNPV. In addition, the risks and costs of product development are complicated and are often commercially confidential. The World Bank engaged experienced independent consultants to provide and initial judgement and on-going monitoring of efficacy. It is also important to note that given the time requirements of vaccine trials and the intrinsic unpredictability of biological Page 8 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) research, strict adherence to predetermined timelines is frequently not achievable. IAVI also shared the cost of these activities across multiple funding sources. Between 2016-2018, the World Bank contribution the implementation of the activities was between 15%-21% of the total project budget. World bank World Bank Other funding Total Funding as % of Funding total 2016 Actuals (July-Dec.) US$ 600,536 US$ 2,853,699 US$ 3,454,235 17% 2017 Actuals (Jan.-Dec.) US$ 1,909,932 US$ 7,380,413 US$ 9,290,345 21% 2018 Actuals (Jan. - Sept.) US$ 1,063,288 US$ 6,077,390 US$ 7,140,678 15% Overall, the costs seem reasonable in comparison with the quality of the activities completed, even though it cannot be quantified, and therefore justifies a substantial rating. Overall Outcome Rating The overall outcome rating for this project is highly satisfactory. Outcome rating Relevance High Efficacy High Efficiency Substantial Overall rating High Page 9 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Other Outcomes and Impacts Due to the nature of this project, there was no gender aspect and the project did not have an immediate, quantifiable impact on poverty. While the project did not work directly with countries, IAVI leveraged its convening power to facilitate discussions in research and development for global health research. This forum was organized by IAVI with the Coalition for Epidemic Preparedness Innovations (CEPI) and the Global Health Innovative Technology (GHIT) Fund as an official side event at the UHC Forum in 2017. The meeting was co-hosted by the Japanese Government, the World Bank, WHO and UNICEF to launch a process for further international collaboration and coordination. The event, titled Strategic Investment in Global Health Vaccine R&D: Strengthening collaboration among global health initiatives and harnessing private sector engagement, established IAVI as a key facilitator in mobilizing private sector financing and institutional strengthening to enhance global capacity in vaccine development for high priority epidemic-prone diseases. The project also contributed to IAVI’s leadership in the field of replication-competent vectors for HIV vaccines, and more broadly accelerated development of a technical platform that will help advance our understanding of HIV as well as guide related vaccine programs for both HIV and other diseases. There were no unintended outcomes or impacts associated with this project. III. KEY FACTORS THAT AFFECTED IMPLEMENTATION AND OUTCOME The project was designed and prepared drawing on the experiences and lessons learned under the previous World Bank supported project, which was rated as highly satisfactory, as well as prior World Bank support to IAVI through the Development Grant Finance (DGF) Facility. While this project was not a straightforward World Bank operation, previous experience concluded that IAVI’s work has been highly relevant and added significant value to the development of an HIV vaccine. The World Bank also engaged two independent global vaccine leaders and experts, Dr. Tetsuro Matano and Dr. Michael P. McCarthy, to provide feedback and endorsement to the design of the project. A previous assessment of IAVI’s financial management and procurement systems concluded that they have strong financial management and fiduciary risk management systems. It also noted that IAVI has the experience, technical capacity and procurement capacity to successfully manage procurement activities. As the activities under this project were being performed by the same organization under similar conditions, the risk assessment undertaken for the previous project was used. The only risk rated as high was the fact that this was an R&D project and the eventual product may not be an effective vaccine. This was taken into account in the development of the PDO and related indicators. IAVI was the recipient of the funding as well as the only implementation partner. It either directly executed or oversaw all activities related to the optimization and testing of the vaccine candidates. The project faced only minor implementation challenges. Staff rotations which contributed to a period of insufficient personnel resulted in slower than expected implementation in some phases of the work. Despite this, the project was completed successfully within the expected implementation timeframe. While one procurement was originally planned, no procurements were ultimately Page 10 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) executed. This did not impact the completion of the project because the materials were procured using a different source of funding. The aforementioned subject matter experts, Drs. Matano and McCarthy, also played active roles in the monitoring and supervision of the project during the implementation phase. The World Bank has a long history of partnership with IAVI and has built a strong investment case for HIV vaccine research. While the project was not intended to complete a fully developed, viable vaccine, it did yield significant knowledge benefits that are already being used for further research. As with all basic science research, there are no guarantees that the eventual product will be an effective and efficient HIV vaccine. This risk was mitigated through managing external and internal expectations by clarifying that the World Bank was supporting basic science research that might or might not produce a viable vaccine, but that it would still contribute to the knowledge in the field. The World Bank had only one TTL managing this project through its life cycle. He was also the TTL of the previous World Bank supported project with IAVI, and therefore, a strong working relationship was already in place. With his background in vaccine development, he was also able to provide technical guidance. The World Bank team conducted regular supervisory visits and provided frequent communication to IAVI on both technical and management issues. There were no factors outside of IAVI’s control that affected project implementation. IV. BANK PERFORMANCE, COMPLIANCE ISSUES, AND RISK TO DEVELOPMENT OUTCOME Monitoring and Evaluation Monitoring and evaluation rating Design Substantial Implementation Substantial Utilization High Overall rating Substantial Relevant PDO indicators were developed at the design phase that were clearly linked to project components and intermediate outcomes. All indicators were binary (‘Yes/No’) which are appropriate for vaccine development and can be objectively assessed. Additional indicators were added to the results framework during restructuring, but the original indicators were not changed. During implementation, the results framework was regularly reviewed and used to monitor progress against the PDO. Due to the nature of vaccine development, as some project components were implemented it was determined that some aspects were not fully efficacious. As a result, activities were modified to respond to new data as it became available which demonstrated that the program was flexible, responsive to on-going monitoring, and ultimately rendered the project successful. The rating of the monitoring and evaluation design and implementation as substantial reflects IAVI’s commitment to designing and adhering to a monitoring system. As new data became available the course of research and some intermediary indicators had to be adjusted. Despite the changes, the PDO was fully and successfully completed; however, due to the structure of World Bank reporting, the results framework could not be updated mid-workstream to Page 11 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) accommodate the changes. This reflects the need to consider different modalities for monitoring activities such as research and development that may have a different structure from more routine investment projects. Utilization of monitoring and evaluation data is rated as high because, as stated above, while there were some flaws in the system to adequately monitor vaccine development, IAVI regularly reported against the indicators and used the results to adjust project priorities and activities as required. Environmental, Social and Fiduciary Compliance No specific safeguard or fiduciary issues arose during the project implementation. The project triggered the Environmental Assessment (OP/BP 4.01) safeguard policy and received a category B environmental rating at the appraisal stage. The initial assessment in the Project Paper states “Key environmental and social risks and impacts relating to IAVI’s activities under the project include: biosafety; occupational health and safety, including exposure to hazardous materials and biohazards; management of hazardous materials; and storage and disposal of hazardous waste and biohazardous/medical waste�. Despite the risks associated with HIV biological and clinical research, the project did not have any large-scale, significant and/or irreversible impacts. IAVI’s has demonstrated capacity to manage environmental and social risks and impacts. IAVI’s existing environmental, health and safety management program includes documented standard operating procedures (SOPs) that address management of key risks and impacts, including a chemical hygiene plan, a laboratory biosafety and security plan, a biosafety manual, a safety SOP, a safety audit checklist, a post exposure plan, and biosafety objectives, among others. The program is managed by a safety committee comprised of twelve members with representatives from each of the laboratory research teams that meets monthly and is responsible for training, recording and monitoring of incidents and revisions to SOPs. An assessment of IAVI's safeguard capacity was undertaken during the previous project (P119051), which concluded that IAVI has adequate rules and procedures, staff, and systems consistent with World Bank safeguard requirements. Furthermore, an Environmental Management Plan (EMP) was prepared in order to manage adverse environmental and social risks and impacts. IAVI demonstrated robust financial management capability throughout the project implementation. The committees of IAVI’s Board of Directors include among others an Audit & Finance Committee, which ensures the integrity and reliability of IAVI’s financial reporting and the organization’s management of risk, as well as being responsible for the independent verification and oversight of whistleblower reports. IAVI has a strong organizational culture for ensuring that funds are used as intended by its head office in New York. It has detailed financial policies, procedures, and regulations, all of which are documented in its Policies and Procedures Manual. Although IAVI’s accounts are audited by an international accounting firm (Gelman, Rosenberg and Freedman), it does not have an internal audit function. This is an area for improvement in order to enhance financial management. The most recent independent audit report was for the year ending December 31, 2017 and was unqualified. The annual financial statements of IAVI are approved by the Finance and Audit Committee and shared with the full Board. Overall, the fiduciary aspect of the project is acceptable and meets the Bank’s internal requirements. There was no issue observed with procurement management. In accordance with the World Bank Procurement Regulations for Borrowers under Investment Project Financing dated July 1, 2016, the Project Procurement Strategy for Development (PPSD) was prepared for the purpose of identifying the most appropriate procurement approach for the project. A procurement plan for an estimate cost of US$156,109 was submitted and a revised procurement plan for an Page 12 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) estimate cost of US$39,660 was also submitted after the restructuring. However, ultimately no items were procured through the grant despite close World Bank support to finalize the procurement activity before the project closed. Due to time constraints, the project team recommended to postpone all procurement activities until the next grant. Bank Performance Bank performance Quality at entry Highly satisfactory Quality of supervision Highly satisfactory Overall rating Highly satisfactory The overall rating of World Bank performance is highly satisfactory. This was also the assessment given by the client. As detailed previously, the World Bank has extensive experiencing working with IAVI on successful projects and the team supporting project development was very experienced in working with IAVI in project design and management as well as providing subject matter expertise in vaccine development. While the strategic approach to this project is unique to the World Bank, the team clearly defined the relevance and potential outcomes of the project and managed expectations internally and externally. The project design and documentation were very strong. There was continuous communication and coordination with IAVI during the implementation stage, and the World Bank was very responsive to and communicative with the client. The relationships between the World Bank and IAVI resulted in a highly successful project. Risk to Development Outcomes Because this grant was for a research project, there is no risk that the scientific data and production know-how gained through the HIV vaccine optimization and testing process will be lost or reversed. However, there is a substantial potential that progress could slow in taking these new scientific findings forward to a viable vaccine for human testing. There are limited sources of funding for HIV and other vaccine development as they require significant financial input and time and do not always align with short funding cycles and program priorities of donors. The progress gained by this grant has been critical to moving forward advancements in developing VSV vaccine vectors, not only for HIV but also for other vaccine platforms. It also provided opportunities for IAVI to provide a coordination platform to bring vaccine stakeholders together and to leverage support from other potential funders including the private sector. V. LESSONS LEARNED AND RECOMMENDATIONS While this project generated a wealth of new scientific information, this report focuses on three higher-level lessons learned. The first is operational management, particularly as it relates to monitoring and evaluation, the second is recommendations for future coordination around research and development projects, and the third is technical recommendations based on the research outcomes. Monitoring and evaluation of R&D projects The last 7 years and two projects implemented by IAVI demonstrate that it is possible to build an M&E framework that is both rigorous and flexible enough to support the research investment case, and to adequately assess ongoing progress during project implementation. Over time, the M&E approach has evolved – and now has i) a more realistic timeline to the achievement of technically complex research outcomes, ii) flexibility within the definitions of indicators that Page 13 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) accommodate evidence-based changes in research direction, while remaining consistent with the development objective and iii) the option for the Bank to review and approve major R&D decision points (“Go-No Go decisions�). The World Bank values its role as a producer of global public goods. Over at least the last 15 years, supporting country capacity to prevent, detect, monitor and respond to infectious diseases has been a consistent policy priority. This was exemplified in the Bank’s leadership in the global response to HIV/AIDS, its foundation membership of Gavi, the Vaccine alliance and the Global Fund, and continues most recently in the development of the Pandemic Emergency Financing Facility. A critical challenge in these efforts has been to support the research and development of novel medicines against “diseases of poverty�. This term captures those diseases which dominate in the developing world, and for which little market incentive exists to promote development of new pharmaceuticals, devices or vaccines. The Bank has invested in several very different models to address these market failures, and to incentivize the development, or price-reduction, of such commodities as a global public good. The market-shaping activities of Gavi are one example, the product development partnerships, including IAVI, are another. The IAVI support has been almost unique in the Bank’s portfolio, in that it has directly supported the most basic, science- driven research and development. A challenge therefore – as this ICR attests – has been to prospectively develop a system to properly monitor and evaluate inherently high-risk research activities. The system developmed is rigorous and flexible - as demonstrated by the effective project supervision and the ongoing support of the Government of Japan as a donor, which has recently committed an additional US$6 million to support this ongoing work. Future R&D projects could explore more innovative M&E approaches – including monitoring the production of sets of generic, but quantifiable, research processes. These could be linked to a results-based payment mechanism. Leveraging trust funds and World Bank coordination for research and development In the second year of this project, it was recognized that based on its successful track record in developing an HIV vaccine, IAVI had a critical role to play in coordinating international partners around vaccine development for other infectious diseases. The non-research objective of this grant provided a platform for sharing lessons learned in the vaccine development as well as leveraging public and private sector resources to complement World Bank, USAID and other funding. Future funding may consider prioritizing the expansion of this coordination role in order to help ensure sustainably and complementary funding for vaccine development. In addition, while this R&D project is quite different from other World Bank lending operations, it does provide an example of a successful Bank and recipient-executed trust fund model with the Government of Japan while will be extended to a third round of funding. This may provide an opportunity to investigate how this model could be replicated to provide opportunities for other Official Development Assistance (ODA) to R&D as well as considering multi-donor trusts which may result in lower transactional costs. Research study outcomes It is somewhat unusual for a financial institution such as the World Bank to fund a pre-clinical vaccine program. Indeed, the World Bank is the primary backer of one of the lead pre-clinical HIV vaccines in the world. The starting position for this vaccine was well founded. The HIV antigen (Env) had recently emerged in the HIV literature as the preferred target for protective antibodies, while the vector (VSV) is becoming a favorite due to its capacity to prime (i. e., generate an effective initial response) of the protective immune system. The vaccine could still fail (maybe Env is insufficient, maybe the VSV- vector will prove hard to manufacture), but even so the fields of HIV research and vaccine development will be enriched. Both the financial support and the regular oversight provided by the World Bank have helped advance this vaccine Page 14 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) program, keeping the project team focused, motivated, and engaged. This should be a feature of similar programs sponsored by the Bank. Also, compared to the pharmaceutical industry, the IAVI VSV-vectored vaccine team is rather small, and might benefit from additional consultation with experts in the field. Helpful critical evaluation is always of benefit and could minimize mis-steps. . Page 15 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) ANNEX 1. RESULTS FRAMEWORK AND KEY OUTPUTS A. RESULTS INDICATORS A.1 PDO Indicators Objective/Outcome: The Project Development Objective is to support the International AIDS Vaccine Initiative (IAVI) in the optimization and testing of one HIV vaccine candidate. Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Vector has been optimized Yes/No N Y Y 04-Jul-2016 30-Jun-2017 30-Jun-2017 Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Vector testing has been Yes/No N Y Y initiated 04-Jul-2016 30-Jun-2017 30-Jun-2017 Comments (achievements against targets): Page 16 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion VSVdG-Env.BG505.1 vaccine Yes/No N N Y Y vector has been evaluated 06-Sep-2017 30-Jun-2018 30-Jun-2018 30-Jun-2018 Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Additional viral vectors have Yes/No N N Y Y been developed 06-Sep-2017 28-Sep-2019 28-Sep-2018 30-Jun-2018 Comments (achievements against targets): A.2 Intermediate Results Indicators Component: (Original Component 1) Five new recombinant vaccines will be generated, their specificity will be tested along with vaccine strain prototype VSVdG-Env. BG505 Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Five genetically modified Yes/No N Y Y VSVdG-Env.BG505 vaccines have been isolated and 10-Feb-2017 30-Jun-2017 30-Jun-2017 characteristics have been Page 17 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) analyzed Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion VSVdG-Env.BG505 mutants Yes/No N Y Y have been isolated after serial passage under conditions that 10-Feb-2017 30-Jun-2017 30-Jun-2017 select for viruses with increased replicative fitness. Mutant virus characteristics have been analyzed. Comments (achievements against targets): Component: (Restructuring Component 1) Comprehensive evaluation of VSVdG-Env. BG505.1 vaccine vector. Production of a vaccine seed. Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Determination of construction Yes/No N N Y Y feasibility and replicative capacity of VSVdG-Env.BG505 20-Jun-2017 02-Apr-2018 02-Apr-2018 30-Jun-2018 with Env in position 2, 3 or 5 Comments (achievements against targets): Page 18 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Initiate VSVdG-Env.BG505 Yes/No N N Y N position 1 vector vaccine rescue in Early Development 20-Jun-2017 28-Sep-2018 28-Sep-2018 28-Sep-2018 Laboratory Comments (achievements against targets): Initiation of VSVDG-Env.BG505 position 1 vector vaccine rescue in Early Development Laboratory (EDL) was postponed. Currently, results from the ongoing primate study indicate that the Env position 1 vector was not an improvement over the Env position 4 prototype vector. This finding along with the observation that the Env position 1 vector appears to grow less efficiently than the position 4 vector led to the decision to not initiate rescue of this vector in the EDL. (From ISR No. 3 dated September 26, 2018) Component: (Restructuring Component 2) Develop vectors with alternative strategic modifications designed to enhance the Env antibody response induced by VSV G-Env vaccines; Develop at least one additional vector Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion VSVdG-Env.BG505 position 1 Yes/No N N Y N vector with Matrix protein (M) modifications that will dampen 20-Jun-2017 01-Jan-2018 01-Jan-2018 28-Sep-2018 the innate immune response rescued Comments (achievements against targets): Given that the data from an ongoing study indicates that the Env position 1 vector was not an improvement over the Env position 4 vector (see the next Intermediate Results Indicator below), a decision was made not to pursue development of an Env position 1 vector with Matrix gene mutations. Instead, Matrix genes have been produced for generating modifications in the Env position 4 vector. The vector has not been rescued but team is preparing to initiate this work. (From ISR No. 3 dated September 26, 2018) Page 19 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion VSVdG-Env.BG505.1 vector Yes/No N N Y N with M modifications evaluated for genetic stability 20-Jun-2017 28-Sep-2018 28-Sep-2018 28-Sep-2018 and replicative capacity Comments (achievements against targets): This objective was not achieved. This objective is linked to indicator above which was modified based on the evaluation of the Env position 1 vector. (From ISR No. 3 dated September 26, 2018) Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Conduct serial passage of VSV Yes/No N N Y Y New Jersey vector to improve replicative capacity and fitness 20-Jun-2017 29-Dec-2017 29-Dec-2017 30-Jun-2018 of the virus Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Evaluate VSV New Jersey Yes/No N N Y Y vector for improved fitness and utility as a vaccine platform 20-Jun-2017 28-Sep-2018 28-Sep-2018 30-Jun-2018 Page 20 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Comments (achievements against targets): Component: (Restructuring Component 3) Develop a new Vero cell line that will support replication of VSV G-Env and produce virus particles bearing a VSV G glycoprotein pseudotype Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Feasibility of VERO-CD4/CCR5 Yes/No N N Y Y cell line also expressing VSV glycoprotein G is demonstrated 20-Jun-2017 29-Dec-2017 29-Dec-2017 30-Jun-2018 Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Initiate VERO CD4/CCR5 VSV G Yes/No N N Y N expressing cell line in Early Development Laboratory 06-Sep-2017 28-Sep-2018 28-Sep-2018 28-Sep-2018 Comments (achievements against targets): A Vero CD4+/CC5+/VSV G+ gene construct was produced and drug-resistant cells containing this set of genes were evaluated under research conditions. Unfortunately, expression of VSV-G was not stable and thus this prototype construct was not suitable for advancing for cell line development in our GMP-compliant Early Development Laboratory (EDL). Several new genes for expressing CD4/CCR5 and VSV G in Vero cells have been designed and gene expression is being evaluated. It is anticipated that one or more of these constructs will be suitable for advancing for cell line development in the EDL. (From ISR No. 3 dated September 26, 2018) Component: (Restructuring Component 4) Presentation of research in conferences and workshops Page 21 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Organize and facilitate meeting Yes/No N N Y Y in conjunction with UHC Forum in December in Tokyo on 06-Sep-2017 01-Jan-2018 01-Jan-2018 30-Jun-2018 Japanese investments in global health R&D Comments (achievements against targets): Component: (Original Component 2) Production of two vaccine candidates and a launch of a comparative vaccine study in India rhesus macaques to analyze safety, immunogenicity, and efficacy. Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion A decision to test new VSVdG- Yes/No N Y Y Env.BG505 vaccines or revise a macaque study to evaluate the 10-Feb-2017 30-Jun-2017 30-Jun-2017 requirement for three doses have been made. Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Candidate vaccines have been Yes/No N Y Y Page 22 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) produced for a preclinical 10-Feb-2017 30-Jun-2017 30-Jun-2017 study. Comments (achievements against targets): Unit of Formally Revised Actual Achieved at Indicator Name Baseline Original Target Measure Target Completion Preclinical study in non-human Yes/No N Y Y primates has been commenced. 10-Feb-2017 30-Jun-2017 30-Jun-2017 Comments (achievements against targets): Page 23 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) Page 24 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) . ANNEX 2. PROJECT COST BY COMPONENT Amount at Approval Actual at Project Percentage of Approval Components (US$M) Closing (US$M) (%) Original Component 1. Vector Optimization. Five new recombinant vaccines will be generated, their specificity will .71 .71 100 be tested along with vaccine strain prototype VSVdG- Env.BG505 Original Component 2. Vector Testing. Production of two vaccine candidates and a launch of a comparative 1.09 1.09 100 vaccine study in Indian rhesus macaques to analyze safety, immunogenicity, and efficacy. Retructuring Component 1. Comprehensive evaluation of VSVdG-Env.BG505.1 vaccine .92 .92 100 vector. Production of a vaccine seed. Restructuring Component 2. Develop vectors with alternative strategic modifications designed to enhance the Env antibody .41 .41 100 response induced by VSV G- Env vaccines; Develop at least one additional vector for VSVdG virus vaccine. Restructuring Component 3. Develop a new Vero cell line that will support replication of .44 .44 100 VSV G-Env and produce virus particles bearing a VSV G glycoprotein pseudotype. Restructuring Component 4. Presentation of research in .02 .02 100 conferences and workshops Total 3.59 3.59 100 Page 25 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) ANNEX 3. RECIPIENT, CO-FINANCIER AND OTHER PARTNER/STAKEHOLDER COMMENTS Borrower’s Evaluation by the International AIDS Vaccine Initiative (IAVI) I. Description of the project The project was built on the past investment by the World Bank from the Japanese trust fund in the vaccine development program using replicating-virus vectors. The candidate vaccine for this project (VSVΔG-Env) was selected based on efficient and rational comparative studies to identify the most potent candidate (partly funded by the Bank/Japan partnership), and the novel design of the vaccine – the way the Envelope of HIV is being expressed – is believed to add substantive value to the field of HIV vaccine R&D. The primary goal of the project was to further optimize the VSV vector, with additional goals of improving future production of vaccine by creating a new cell-line from which the virus used for vaccine will be produced, and to develop additional VSV vector platform. There is a strong rationale for the investment in VSV vector optimization and additional activities undertaken in this project since not only the project brings the world closer to an effective HIV vaccine, but also because the VSV has been identified and used as an effective vaccine platform for numerous diseases, including Ebola, and hence the outcome of the project has potential utility beyond HIV. A small non-R&D component was added in the second year in which IAVI collaborated with other global R&D partners to share the experience and expertise in vaccine R&D at a conference in Tokyo. II. Assessment of the outcome The outcome of the program was highly satisfactory. Most of the deliverables were completed on time. The deliverables that were not met were based on the rational decision stemming from the data and results of the experiment. The operation of the program was also highly satisfactory. The project remained on budget and funds were used efficiently. There were four major components to the program. Component 1: Involved a comprehensive evaluation of a new HIV vaccine candidate and if appropriate production of material that could be advanced further. A new vaccine candidate was evaluated. However, the candidate did not show improved efficacy and is not being pursued. Component 2: Involved development of additional new HIV vaccine candidates with strategic modifications designed to enhance vaccine efficacy. Several new vaccine candidates including a new vector platform were evaluated. The New platform based on a different viral backbone is being further characterized and developed. Component 3: Involved development a cell line that will support manufacture of the HIV vaccine. Several versions were evaluated and are being further developed. Component 4. Involved dissemination of knowledge during the 2017 Universal Health Coverage Forum in Tokyo. On December 15th, 2017, IAVI, along with CEPI and GHIT Fund, organized an official side event on the margin of the UHC Forum 2017. The meeting was co-hosted by the Japanese Government, the World Bank, WHO and UNICEF. The side event was conceived as a kick-off meeting to launch a process of further international collaboration and coordination among global R&D initiatives. Page 26 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) III. Key factors Although supporting vaccine R&D via trust fund remains a unique case within the World Bank’s portfolio, IAVI believes that the key factors in the success of the project is precisely the long-standing, three-way partnership among the donor government, global multilateral agency with expertise and administrative resources, and the highly technical, non-for-profit implementing entity. In addition to the administrative oversight that the World Bank provided, the continued presence of scientific expertise within the Bank team was critical in the successful implementation of the project. Furthermore, IAVI’s track record in transparency and competency in delivering the expected outcome had built trust in the donor, and in part led to the non-R&D component of the project in the second year in which IAVI led the collaborative work with other global product development partners to maximize the investment by the donor government. Lastly, the importance of vaccine R&D has re-emerged as a central strategy in global health emergency preparedness, and in achieving SDG health goals. IAVI’s expertise and experience in HIV vaccine R&D and the scientific innovations in the field are now proven to be applicable beyond HIV, to other infectious diseases such as Lassa fever. The potential synergy with investments in other emerging infectious diseases strengthened the rationale for the donor government in sustaining investment in IAVI’s project. IV. Evaluation of borrower’s performance IAVI believes its performance during the preparation and implementation was highly satisfactory. IAVI was responsive to the Bank’s new guidance and provided information and reporting on timely manner. V. Lessons learned The non-human primate (NHP) study outcomes demonstrated that the vaccine material was less effective than it had been in previous studies. IAVI now believes that this is due to changing the cell line used to produce the vaccine material. Several lessons were learned from this including: Vector Production: The impact of changing the cell line used to produce vaccine material on vaccine material composition was underestimated. This was due to the limited production experience with the new Vero CD4/CCR5 cell line, VeRT3.EDL, prior to using these cells to produce vaccine material for the NHP study. Optimization of the vaccine production process for new cell lines is critical. The process should be developed and evaluated for quality and composition of the material that is produced as well as robustness and reproducibility. It is also critical to have reliable and sensitive assays available for testing vaccine material, as well as an understanding of the profile of the vaccine material. The production process and analytical assays should be ‘pressure test’ early in their development to uncover problems sooner rather than at a later critical stage such as production of material for NHP studies, production of a seed virus, or manufacturing of clinical trial material. Critical Quality Attributes of Vaccine Material: The key quality attributes affecting vaccine material performance were not completely understood when the material to support the NHP study was produced. Based on the assays available at the time of production, the material appeared similar to what was used in the earlier NHP1401 study. IAVI now has an improved Comparative Infectivity Assay (CIA) and has developed additional new analytical methods (such as flow virometery using the Apogee instrument) that provide them with a greatly expanded Page 27 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) assessment of the vaccine material. IAVI is further developing and expanding these methods to provide a profile of the composition of the batch of material not just a single average value for the material. For viral vector vaccines, in particular HIV vaccines, there is a need to be able to assess the quality and composition of the material. The quality and composition of the material is critical for the vaccine to elicit a protective immune response versus a non-protective although often robust immune response. VI. Proposal for future operation IAVI believes the unique three-way partnership functioned positively and proposes the continuation of such arrangement in the future. The World Bank was able to provide much needed technical expertise and advice to the Ministry of Finance, which is the responsible agency for funding for IAVI. In turn, the partnership with the Bank provided legitimacy to the donor government for its support to IAVI to the Japanese tax payers. A partnership with the Bank signals that a vaccine for HIV/AIDS and other pandemic diseases is a global public good and therefore the use of ODA funds is justified. IAVI understands that there is internal debate within the Bank to question the operational model -- that a trust fund focusing on product development is too much of an outlier. However, the involvement of the Work Bank, as the world’s primary development agency, in the development of global public goods such as vaccines, is increasingly relevant given the heightened demand to develop necessary medical tools to fight future unknown pandemics. Partnership with IAVI is an important precedent and example of how the Bank can leverage donor’s support for product development. IAVI welcomes the commitment from the donor for the next round of support over multiple years, based on the appreciation that R&D is a complex and long-term project, which will minimize the inefficiency of repeating single- year commitments. IAVI believes that it is a testament to an effective partnership between a donor government, a highly technical non-profit organization and the World Bank, in which the Bank provided much needed technical and administrative supervision, coordination, and most importantly, legitimacy to a truly global effort to develop a global public good. VII. Sustainability HIV vaccine research and development funding is exceptionally difficult to obtain and has been for some time. Donor and funder budgets are tight, their priorities shift, and the pace of progress may not be aligned with expectations. The World Bank’s long-term support and commitment to this ‘risky’ replicating vector concept has been essential in making meaningful progress on VSV vaccine vectors. IAVI remains dedicated to advancing a VSV-HIV vaccine as well as further developing the VSV platform and its application to other emerging infectious diseases. To this end IAVI thanks the World Bank for its continued support of the VSV-HIV vaccine program and the recent award of a new grant supporting almost three years of research to further develop the tools required to bring this critically needed vaccine to evaluation in a clinical trial. In addition, IAVI has been awarded grants from the NIH and CEPI which also support the VSV-HIV program and the VSV vector platform as a vaccine candidate to development a Lassa virus vaccine. IAVI continues to evaluate new funding opportunities to support the VSV program and ensure sustainability of the IAVI resources dedicated to the advancement of a vaccine against HIV. Page 28 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) ANNEX 4. LIST OF DOCUMENTS REVIEWED • Project Information Document (PID)/concept note August 2016 • Integrated Safeguards Data Sheet August 2016 • Environmental Management Plan January 2017 • IAVI proposed workplan and budget January 2017 o Technical review (Matano & McCarthy) & IAVI response January 2017 • Project Paper (PAD) February 8, 2017 • Procurement Plan February 2017 • Grant approval notification February 23, 2017 • Grant disbursement instructions February 23, 2017 • Aide Memoire April 2017 o Technical reviews (Matano & McCarthy) April/May 2017 • ISR May 2017 • Restructuring Paper September 2017 • Procurement Plan after restructuring September 2017 • Year 1 Progress Report August 2017 o Technical review (Matano & McCarthy) Sept/Oct 2017 • Grant amendment notification October 2017 • ISR November 2017 • Technical review on progress toward close-out (McCarthy) June 2018 • Results framework updated indicators September 2018 • ISR September 2018 • Year 2 progress report November 2018 Page 29 of 30 The World Bank Support to Research and Development at the International AIDS Vaccine Initiative (P161232) ANNEX 5. Team Composition Bank’s Team Name Role Specialization Unit Phone No. Location BANGKOK, Robert Oelrichs Team Leader Molecular virology GHN19 5778+8363 / THAILAND Blandine Marie Wu Procurement Specialist -- GGOSC 5780+3030 / PARIS, FRANCE Chebili Financial Management WASHINGTON, Madhavan Balachandran -- GGOSC 202-473-8129 Specialist DC WASHINGTON, Agnes I. Kiss Social Specialist -- OPSSP 202-458-7180 DC WASHINGTON, Brandon Enrique Carter Environmental Specialist -- GENA3 473-9858 DC WASHINGTON, Maria Lourdes Pardo Counsel -- LEGDF 458-8781 DC WASHINGTON, Mariko Fukao Team Member -- GHNGE 5220+32416 / DC WASHINGTON, Minh Thi Hoang Trinh Team Member -- GHN19 458-7393 DC WASHINGTON, Sara Halstead Hersey ICR author GHNGE 5220+35424 / DC Extended Team Name Title Organization Office Location Michael McCarthy Product Development Specialist -- 3016918353 ,United States National Institute of Tetsuro Matano Director Infectious Diseases, 81352851111 ,Japan Japan Page 30 of 30