Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Macmillan Publishers Limited.
Abstract
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.
Description
CAPRISA, 2014.
Keywords
AIDS Vaccines/chemistry., AIDS Vaccines/immunology., Amino Acid Sequence.
Citation
Doria-Rose, N.A., Schramm, C.A., Gorman, J., Moore, P.L., Bhiman, J.N., DeKosky, B.J., Ernandes, M.J., Georgiev, I.S., Kim, H.J., Pancera, M. and Staupe, R.P. 2014. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509(7498), 55-62.