Lessons from HIV-1 vaccine efficacy trials

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Four human immunodeficiency virus type 1 (HIV-1) vaccine concepts have undergone six efficacy trials without success.
• The RV144 trial, the only efficacy study to show modest vaccine efficacy, identified immune correlates of risk.

Purpose of the Study:

• To review lessons learned from past HIV-1 vaccine efficacy trials.
• To guide the development of novel HIV-1 vaccine candidates and future research steps.

Main Methods:

• Review of historical HIV-1 vaccine efficacy trials.
• Analysis of scientific and programmatic lessons learned.
• Evaluation of emerging HIV-1 vaccine concepts and technologies.

Main Results:

• The RV144 trial demonstrated modest vaccine efficacy and identified immune correlates of risk.
• New approaches, including Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 and cytomegalovirus (CMV)-vectored vaccines, are advancing to efficacy and Phase I studies.
• Future trials face challenges due to effective nonvaccine prevention strategies.

Conclusions:

• Accelerating the development of next-generation HIV-1 vaccines requires increased industry involvement, resource mobilization, and robust preclinical studies.
• Lessons from past trials are crucial for refining hypotheses and strategies for future HIV-1 vaccine development.