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Duke Core Neutralizing Antibody Laboratory for AIDS Vaccine Research & Development

Duke Core Neutralizing Antibody Laboratory for AIDS Vaccine Research & Development. 1988 - Present NIH AIDS Vaccine Evaluation Group (AVEG, 1988-1999) NIH HIV Vaccine Trials Network (HVTN, 1999-Present) 1992- Present NIH Preclinical Immunology Laboratory for AIDS Vaccine

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Duke Core Neutralizing Antibody Laboratory for AIDS Vaccine Research & Development

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  1. Duke Core Neutralizing Antibody Laboratory for AIDS Vaccine Research & Development 1988 - Present NIH AIDS Vaccine Evaluation Group (AVEG, 1988-1999) NIH HIV Vaccine Trials Network (HVTN, 1999-Present) 1992- Present NIH Preclinical Immunology Laboratory for AIDS Vaccine Research & Development Major Goals: • Study the immune responses elicited by candidate vaccines • Compare the immune responses induced by vaccination to those induced by infection as a benchmark • Identify immunologic correlates of protection • Gain insights for future vaccine designs

  2. STAGES OF HIV-1 ENTRY AS TARGETS FOR NEUTRALIZING ANTIBODIES Separate components of fusion Fusion competent intermediate T cell Virus-cell fusion T cell CCR5 T cell CD4 HIV-1 HIV-1 gp120 gp41 HIV-1 Neutralizing antibodies are entry inhibitors

  3. STAGES OF HIV-1 ENTRY AS TARGETS FOR NEUTRALIZING ANTIBODIES Separate components of fusion Fusion competent intermediate T cell Virus-cell fusion T cell CCR5 T cell CD4 HIV-1 HIV-1 gp120 gp41 HIV-1 Neutralizing antibodies are entry inhibitors

  4. STAGES OF HIV-1 ENTRY AS TARGETS FOR NEUTRALIZING ANTIBODIES Separate components of fusion Fusion competent intermediate T cell Virus-cell fusion T cell CCR5 T cell CD4 X HIV-1 HIV-1 gp120 gp41 HIV-1 Neutralizing antibodies are entry inhibitors

  5. STAGES OF HIV-1 ENTRY AS TARGETS FOR NEUTRALIZING ANTIBODIES Separate components of fusion Fusion competent intermediate T cell Virus-cell fusion T cell CCR5 T cell CD4 HIV-1 HIV-1 gp120 gp41 HIV-1 Neutralizing antibodies are entry inhibitors

  6. STAGES OF HIV-1 ENTRY AS TARGETS FOR NEUTRALIZING ANTIBODIES Separate components of fusion Fusion competent intermediate T cell Virus-cell fusion T cell CCR5 T cell CD4 X HIV-1 HIV-1 gp120 gp41 HIV-1 Neutralizing antibodies are entry inhibitors

  7. Lights “ON” Molecular cloning LUC Tzm-bl cell + pEnv DNA pHIVEnv DNA Infection Transfection 293T cell Pseudovirus SEQUENTIAL EVENTS IN DETECTING NEUTRALIZATION OF ENV-PSEUDOVIRUSES IN TZM-BL CELLS

  8. Lights “OFF” Molecular cloning Tzm-bl cell + pEnv DNA No infection pHIVEnv DNA LUC Y Y Y Antibody Y Y Transfection 293T cell Pseudovirus SEQUENTIAL EVENTS IN DETECTING NEUTRALIZATION OF ENV-PSEUDOVIRUSES IN TZM-BL CELLS

  9. SPECTRUM OF NEUTRALIZATION-SENSITIVITIES TCLA & some 1o isolates Desired reference strains Neutralized by sera from vaccinees Relative abundance V3 sensitivity Low Average High Overall neutralization-sensitivity

  10. Other Efforts in Progress • Develop standard panels of molecularly cloned Env-pseudotyped reference strains of HIV-1 for each major genetic subtype of the virus, including additional panels that correspond to vaccine trial sites. • Neutralization serotype discovery. • Design and implement a global laboratory network for standardized assessments of vaccine-elicited neutralizing antibody responses (Africa, India, South America, China, Thailand, Europe).

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