Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
By N. Doria-Rose, Chaim A. Schramm, J. Gorman, P. Moore, J. Bhiman, Brandon J Dekosky, Michael J. Ernandes, Ivelin S. Georgiev, Helen J. Kim, M. Pancera and 35 more. Nature, 2014
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Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01–12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.
Subfields: Immunology, Virology
View Paper: https://www.semanticscholar.org/paper/7d03dd7b2bab77346d3f4bd078eeb168340dc4b3
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In Immunology
Citations in the corpus
- Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8 (2016, methodology): “Initial tests with this Vgenereverted antibody showed no neutralization against a set of HIV-1 pseudoviruses, while neutralization was observed with a substantially reverted antibody with no mutations in the framework regions of the antibody and with ten mutations in CDR H1 and CDR H2 and two mutati”
- Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1 (2014, background): “Over the last 5 years many broad and potent neutralizing mAbs have been identified [20,33,38,39,40,41,42,43,44] and it has been postulated that combining these mAb could provide protection against a wider range of strains whether by traditional passive transfer at much lower doses than previously im”
- T follicular helper cell differentiation, function, and roles in disease (2014, background): “Some of these antibodies develop new disulfide bonds that stabilize long CDR loops (Doria-Rose et al., 2014).”