Prevention Keynote: HIV Vaccine Development: How will we translate scientific opportunity into public health impact?

  • Mark Feinberg, MD, PhD
    President and CEO, International AIDS Vaccine Initiative

Presentation Slides

  • HIV Vaccine Development: How will we translate scientific opportunity into public health impact?
  • Topics for discussion
  • HIV/AIDS Continues to Devastate
  • PEPFAR
  • Sub-Saharan Africa is the epicenter of the persistent HIV/AIDS epidemic
  • Disproportionate Success by Age In Reducing  New HIV Infections Over the Course of the Response
  • The growing “youth bulge” in Sub-Saharan Africa
  • The rationale for “90:90:90 target” and the attendant “5 year window”
  • “Without an AIDS vaccine, we will not end AIDS.”
  • An effective HIV vaccine would be transformative
  • Elements and Typical Timelines for Vaccine Development
  • The Critical importance of Alignment and Integration (an “end to end” view)
  • IAVI Mission
  • IAVI’s Focus and Facilitation
  • The IAVI Vaccine Product Development Center (VxPDC)
  • BMGF HIV grantees supported via the IAVI VxPDC
  • Additional external projects supported via IAVI VxPDC
  • Traditional vaccine approaches have failed for HIV –the most challenging vaccine target ever attempted
  • Relative genetic variability of HIV
  • Host cell
  • Neutralizing Ab
  • The HIV Env spike, sole target of nAbs,  is a metastable trimer of heterodimers
  • The HIV Env glycoprotein: a daunting target for antibody neutralization
  • Current AIDS vaccine development approaches
  • The history of testing AIDS vaccine concepts in efficacy trials
  • In 2009, the RV144 study in Thailand provided evidence that an AIDS vaccine is possible
  • Thai Phase III HIV Vaccine Trial (RV144) Summary
  • HVTN702 – Seeking to replicate and extend RV144 results in South Africa
  • Vaccination regimens shown to induce non-neutralizing IgG associated with resistance to SIV  or SHIV challenge virus
  • High Level Target Product Profile Goal:Prophylactic vaccine offering protection against all clades of HIV-1 through an heterologous prime boost regimen
  • Expanding Breadth of Immune Responses
  • Proof-of-Concept Study
  • Seeking a Rational Approach to HIV Vaccine Design
  • Reverse vaccinology 2.0
  • The Antibody Project: IAVI Protocol G
  • Despite the evasion tactics by HIV Env, up to 20% of chronically-infected individuals develop broad serum neutralization
  • Host-characteristics associated with  neutralization breadth and potency
  • HIV broadly neutralizing antibodies have rare features compared to antibodies elicited by existing vaccines based on antibody features frequency (AFF) analysis
  • Affinity maturation of broadly neutralizing antibodies in natural infection (CAP256 lineage as an example)
  • CAP256 lineage arises following super infection, but escape rapidly emerges
  • Epitopes Recognized by bnAbs
  • Breadth and Potency of Prototype bnAbs from Natural HIV Infection
  • PGT121 and PGDM1400 in Combination Provide Excellent Coverage of a 106-virus Panel
  • The First Study of Antibody Mediated Prevention (AMP)
  • bnAb candidates being considered for  preventative efficacy evaluation
  • Primary approaches to induce bNAbs by vaccination
  • Germline-reverted broadly neutralizing antibodies vs. identifying unmutated common ancestor
  • Germline-reverted broadly neutralizing antibodies do not bind to HIV Env
  • Germline targeting approaches for HIV vaccine design
  • Germline-targeting immunogen design
  • Can Germline-targeting Immunogens Prime Low Frequency bNAb Precursors?
  • Can germline-targeting immunogens prime low frequency precursors?
  • Cell
  • Questions for the germline targeting approach
  • The continuing value of viral vaccine vector development
  • Effector T cells induced by persistent RhCMV-SIV infection prevents SIV disease
  • State of the Field: Replicating Vectors VSV-HIV Vaccines
  • VSVDG-Env was compared against a more typical  VSV vector (VSV-G6-Env) in the initial preclinical efficacy study
  • A replication-competent vesicular stomatitis virus (VSV) chimera induces non-neutralizing Abs associated with resistance to mucosal SHIV infection
  • Optimizing HIV Vaccine Product Development
  • Rational Approaches to HIV Vaccine Design
  • mRNA vaccines have the potential to address many of the shortcomings of current vaccine platforms
  • If mRNA could be a vaccine… it would provide a platform
  • Targets for mRNA Vaccines Optimization
  • Examples of approaches taken by different companies
  • Moderna Lipid Nanoparticle (LNP) manufacturing process
  • MERS coronavirus
  • MERS-CoV - Neutralizing antibody titer
  • 1 and 2 doses confer robust protection in the Nose, Throat and BAL
  • mRNA Vaccines Outstanding Questions
  • Synthetic DNA Delivery Technology Represents an Important and Unique Platform for In vivo
  • Phase IIb Efficacy Study VGX-3100 treated Patients Cleared Infection
  • VGX-3100 Generates CD8+T Cells that Infiltrate into the Cervical Tissue and Associate with Clinical Outcomes
  • High Level Summary
  • Global Cervical Cancer Mortality
  • GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]*
  • Prophylactic Efficacy: 100% Efficacious Against HPV 16- and 18-Related Cancer Precursors
  • Consequences of a 10 year delay in HPV vaccine introduction
  • Rwanda HPV National Vaccine Introduction Program
  • Countries with publicly funded national human papillomavirus vaccination programs (2006-2015)
  • Global Rotavirus Mortality
  • RotaTeq®: Merck’s Rotavirus Vaccine
  • 2014-2016 Ebola Virus Outbreak
  • V920: Merck’s rVSVΔG-ZEBOV-GP Vaccine
  • Partnerships and Alliances to Develop V920
  • Phase III Ring Vaccination Trial in Guinea Final Results Dec 2016
  • Where are we on Ebola development efforts?
  • An unprecedented response to a global health emergency
  • CEPI – Coalition for Epidemic Preparedness Innovations
  • What is CEPI?
  • How will CEPI work?
  • CEPI’s end-to-end gap-filling role: a sustainable partnership approach
  • We can best overcome key HIV vaccine development challenges ahead by working together
  • AIDS: Taking a Long-Term View
  • HIV/AIDS Continues to Devastate
  • Cecilia Kamura, Age 6, Robertsport, Liberia
  • Imagine a world without AIDS
  • IAVI
  • Funding for the studies referenced in this  presentation generously provided by: