Browsing by Author "Binley, James M."

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Broad neutralization of human immunodeficiency virus type 1 mediated by plasma antibodies against the gp41 membrane proximal external region.
(American Society for Microbiology., 2009) Gray, Elin Solomonovna.; Madiga, Maphuti C.; Moore, Penelope L.; Mlisana, Koleka Patience.; Abdool Karim, Salim Safurdeen.; Binley, James M.; Shaw, George M.; Mascola, John R.; Morris, Lynn.
We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies. Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases, respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design.
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
(Macmillan Publishers Limited., 2014) Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason.; Moore, Penelope L.; Bhiman, Jinal N.; DeKosky, Brandon J.; Ernandes, Michael J.; Georgiev, Ivelin S.; Kim, Helen J.; Pancera, Marie.; Staupe, Ryan P.; Altae-Tran, Han R.; Bailer, Robert T.; Crooks, Ema T.; Druz, Aliaksandr.; Garrett, Nigel Joel.; Hoi, Kam H.; Kong, Rui.; Louder, Mark K.; Longo, Nancy S.; McKee, Krisha.; Nonyane, Molati.; O’Dell, Sijy.; Roark, Ryan S.; Rudicell, Rebecca S.; Schmidt, Stephen D.; Sheward, Daniel J.; Soto, Cinque.; Wibmer, Constantinos Kurt.; Yang, Yongping.; Zhang, Zhenhai.; Mullikin, James C.; Binley, James M.; Sanders, Rogier W.; Wilson, Ian A.; Moore, John P.; Ward, Andrew B.; Georgiou, George.; Williamson, Carolyn.; Abdool Karim, Salim Safurdeen.; Morris, Lynn.; Kwong, Peter D.; Shapiro, Lawrence.; Mascola, John R.
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.
Mapping polyclonal HIV-1 antibody responses via next-generation neutralization fingerprinting.
(Public Library of Science., 2017) Doria-Rose, Nicole A.; Altae-Tran, Han R.; Roark, Ryan S.; Schmidt, Stephen D.; Sutton, Matthew S.; Louder, Mark K.; Chuang, Gwo-Yu.; Bailer, Robert T.; Cortez, Valerie.; Kong, Rui.; McKee, Krisha.; O'Dell, Sijy.; Wang, Felicia.; Abdool Karim, Salim Safurdeen.; Binley, James M.; Connors, Mark.; Haynes, Barton F.; Martin, Malcolm A.; Montefiori, David Charles.; Morris, Lynn.; Overbaugh, Julie.; Kwong, Peter D.; Mascola, John R.; Georgiev, Ivelin S.
Abstract available in pdf.