HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.
In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.
Duke Scholars
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Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- X-Ray Diffraction
- Viral Vaccines
- Protein Conformation
- Mutation
- Models, Molecular
- Immunoglobulin Variable Region
- Immunization, Secondary
- Humans
- HIV-1
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- X-Ray Diffraction
- Viral Vaccines
- Protein Conformation
- Mutation
- Models, Molecular
- Immunoglobulin Variable Region
- Immunization, Secondary
- Humans
- HIV-1