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HIV-1 infections with multiple founders associate with the development of neutralization breadth
Eric Lewitus1,2, Samantha M Townsley1,2, Yifan Li1,2
1U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Plos Pathogens
|March 18, 2022
Summary
Infection with multiple HIV variants early in HIV-1 infection promotes broadly neutralizing antibody (bnAb) development. This suggests a novel vaccine strategy using diverse antigens to elicit bnAbs.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Developing effective HIV-1 vaccines requires eliciting broadly neutralizing antibodies (bnAbs).
- Understanding the relationship between early viral genetics and antibody response is crucial for vaccine design.
- HIV-1 envelope (env) sequence diversity during acute infection may influence the development of neutralization breadth.
Purpose of the Study:
- To investigate the association between HIV-1 env genetic diversity at acute infection and the development of neutralization breadth.
- To determine if the multiplicity of HIV-1 founder variants impacts antibody response.
- To explore potential novel HIV vaccine strategies based on early viral genetic diversity.
Main Methods:
- Analysis of HIV-1 env sequences from individuals in a prospective acute HIV-1 cohort (n=70).
- Comparison of env diversity between individuals who developed bnAbs and those with limited neutralization breadth.
- Assessment of founder variant multiplicity in relation to neutralization breadth.
- Analysis of env sequences from RV144 vaccine trial placebo recipients (n=56) and participants (n=126) to confirm findings and assess heritability.
Main Results:
- Individuals who developed bnAbs were more likely to be infected with multiple HIV-1 founder variants compared to those with limited breadth.
- Significantly higher env diversity was observed at HIV-1 diagnosis in participants who later developed bnAbs (p = 0.012).
- The association between founder multiplicity and neutralization breadth was also observed in RV144 trial participants.
Conclusions:
- The presence of multiple, slightly divergent HIV-1 variants during acute infection may promote the induction of bnAbs.
- Founder variant multiplicity is associated with the development of broad HIV-1 neutralization.
- A potential HIV vaccine strategy involves initial immunization with a cocktail of minimally divergent antigens to induce bnAbs.
