Losing Less in Translation: Relating the Preclinical Evidence Base for Active and Passive Immunity to Prevention of...

Area of Science:

• Immunology
• Preclinical Research
• Vaccinology

Background:

• Nonhuman primate (NHP) models are crucial for HIV-1 therapeutic and prophylactic intervention development.
• Despite preclinical success, major HIV vaccine efficacy trials and Antibody-Mediated Prevention (AMP) trials have failed to meet efficacy criteria.
• This highlights a critical gap between NHP model results and clinical trial outcomes.

Purpose of the Study:

• To discuss factors influencing the consistency of NHP experiments.
• To identify ways to improve translation between preclinical and clinical settings for HIV-1 vaccine development.
• To evaluate the value of AMP trials as a benchmark for humoral immune responses.

Main Methods:

• Review of NHP model efficacy in HIV-1 vaccine development.
• Analysis of outcomes from major HIV vaccine efficacy trials.
• Examination of Antibody-Mediated Prevention (AMP) trial data (HVTN 703, 704) involving VRC01 antibody passive immunization.
• Discussion of factors affecting preclinical-to-clinical translation for active and passive vaccine regimens.

Main Results:

• Both active and passive vaccination strategies successful in NHPs have not translated to sufficient clinical benefits.
• The AMP trials serve as a critical benchmark for assessing the clinical potential of vaccine-induced or passively administered humoral immunity.
• Discrepancies between NHP models and human trials necessitate a re-evaluation of modeling strategies.

Conclusions:

• Bridging the gap between NHP models and human clinical trials is essential for advancing HIV-1 vaccine development.
• The AMP trials provide valuable insights into the clinical prospects of humoral immune responses against HIV-1.
• Continued research into preclinical modeling of humoral immunity is vital for future HIV-1 interventions.