HIV-1 bNAb Vaccinal Effect-An Underachieving Goal?

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Broadly neutralizing monoclonal antibodies (bNAbs) are being investigated for their potential to induce endogenous immune responses against HIV-1, a phenomenon termed a 'vaccinal effect'.
• Clinical trials have reported modest increases in anti-HIV-1 neutralizing antibodies or T cell responses after bNAb administration in people living with HIV.
• However, the mechanisms underlying this vaccinal effect remain unclear, and results are not consistently replicated.

Purpose of the Study:

• To review clinical and pre-clinical nonhuman primate studies evaluating the vaccinal effects of HIV-1/SIV monoclonal antibodies.
• To discuss the strengths and limitations of existing studies.
• To outline considerations for future research, including appropriate controls and endpoints for investigating vaccinal effects.

Main Methods:

• Review of published clinical and nonhuman primate studies on bNAbs and vaccinal effects.
• Analysis of immune response data from these studies.
• Discussion of challenges in measuring vaccinal effects in human trials.

Main Results:

• Evidence for vaccinal effects from bNAb administration is inconsistent and the magnitude of immune response enhancement is generally modest.
• Difficulties in sensitive measurement of vaccinal effects in human trials contribute to inconsistency.
• Pre-clinical and clinical studies have limitations in demonstrating a clear and reproducible vaccinal effect.

Conclusions:

• The elicitation of vaccinal effects by bNAbs to date has been disappointing.
• Future studies require careful design with appropriate comparators and sensitive immunogenicity assays to conclusively interpret potential vaccinal effects.
• Investigating immune response characteristics of elite controllers may provide relevant endpoints for durable HIV-1 suppression.