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Curr Opin HIV AIDS. 2014 May;9(3):210-6. doi: 10.1097/COH.0000000000000057.

Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection.

Author information

1
aEmory Vaccine Center at Yerkes National Primate Research Center bDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA cCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Services dUniversity of the Witwatersrand, Johannesburg eCenter for the AIDS Program of Research (CAPRISA), South Africa.

Abstract

PURPOSE OF REVIEW:

Detailed genetic and structural characterization has revealed that broadly neutralizing antibodies (bnAbs) against HIV-1 have unusually high levels of somatic hypermutation, long CDRH3 domains, and the ability to target one of four sites of vulnerability on the HIV-1 envelope (Env) glycoproteins. A current priority is to understand how bnAbs are generated during natural infection, and translate this information into immunogens that can elicit bnAb following vaccination.

RECENT FINDINGS:

Strain-specific neutralizing antibodies can acquire broad neutralizing capacity when the transmitted/founder Env or a specific Env variant is recognized by an unmutated rearranged germline that has the capacity to develop bnAb-like features. This event could be relatively infrequent, as only certain germlines appear to possess inherent features needed for bnAb activity. Furthermore, the glycosylation pattern and diversity of circulating HIV-1 Envs, as well as the state of the B-cell compartment, may influence the activation and maturation of certain antibody lineages.

SUMMARY:

Collectively, studies over the last year have suggested that the development of HIV-1 Env immunogens that bind and activate bnAb-like germlines is feasible. However, more information about the features of Env variants and the host factors that lead to breadth during natural infection are needed to elicit bnAbs through immunization.

PMID:
24662931
PMCID:
PMC4068799
DOI:
10.1097/COH.0000000000000057
[Indexed for MEDLINE]
Free PMC Article

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