Browsing by Author "Bhiman, Jinal N."

Now showing 1 - 9 of 9

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.
Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape.
(Nature Publishing Group., 2012) Moore, Penelope L.; Gray, Elin Solomonovna.; Wibmer, Constantinos Kurt.; Bhiman, Jinal N.; Nonyane, Molati.; Hermanus, Tandile.; Sheward, Daniel J.; Bajimaya, Shringkhala.; Abrahams, Melissa-Rose.; Tumba, Nancy Lola.; Ping, Li-Hua.; Ngandu, Nobubelo K.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Swanstrom, Ronald.; Seaman, Michael S.; Williamson, Carolyn.; Morris, Lynn.;
Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.
New member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency.
(American Society for Microbiology., 2016) Doria-Rose, Nicole A.; Bhiman, Jinal N.; Roark, Ryan S.; Schramm, Chaim A.; Gorman, Jason.; Chuang, Gwo-Yu.; Pancera, Marie.; Cale, Evan M.; Ernandes, Michael J.; Louder, Mark K.; Asokan, Mangaiarkarasi.; Bailer, Robert T.; Druz, Aliaksandr.; Fraschilla, Isabella R.; Garrett, Nigel Joel.; Jarosinski, Marissa.; Lynch, Rebecca M.; McKee, Krisha.; O’Dell, Sijy.; Pegu, Amarendra.; Schmidt, Stephen D.; Staupe, Ryan P.; Sutton, Matthew S.; Wang, Keyun.; Wibmer, Constantinos Kurt.; Haynes, Barton F.; Abdool Karim, Salim Safurdeen.; Shapiro, Lawrence.; Kwong, Peter D.; Moore, Penelope L.; Morris, Lynn.; Mascola, John R.
Abstract available in pdf.
Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation.
(Nature Publishing Group., 2018) Johnson, Erik L.; Doria-Rose, Nicole A.; Gorman, Jason.; Bhiman, Jinal N.; Schramm, Chaim A.; Vu, Ashley Q.; Law, William H.; Zhang, Baoshan.; Bekker, Valerie.; Abdool Karim, Salim Safurdeen.; Ippolito, Gregory C.; Morris, Lynn.; Moore, Penelope L.; Kwong, Peter D.; Mascola, John R.; Georgiou, George.
Abstract available in pdf.
Structural constraints of vaccine-induced tier-2 autologous HIV neutralizing antibodies targeting the receptor-binding site.
(Cell Press., 2016) Bradley, Todd.; Fera, Daniela.; Bhiman, Jinal N.; Eslamizar, Leila.; Lu, Xiaozhi.; Anasti, Kara.; Zhang, Ruijun.; Sutherland, Laura L.; Scearce, Richard M.; Bowman, Cindy M.; Stolarchuk, Christina.; Lloyd, Krissey E.; Parks, Robert.; Eaton, Amanda.; Foulger, Andrew.; Nie, Xiaoyan.; Abdool Karim, Salim Safurdeen.; Barnett, Susan.; Kelsoe, Garnett.; Kepler, Thomas B.; Alam, Shabnam Munir.; Montefiori, David Charles.; Moody, Michael Anthony.; Liao, Hua-Xin.; Morris, Lynn.; Santra, Sampa.; Harrison, Stephen C.; Haynes, Barton F.
Abstract available in pdf.
Structure and recognition of a novel HIV-1 gp120-gp41 interface antibody that caused MPER exposure through viral escape.
(Public Library of Science., 2017) Wibmer, Constantinos Kurt.; Gorman, Jason.; Ozorowski, Gabriel.; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie.; Smira, Ashley.; Joyce, M. Gordon.; Ndabambi, Nonkululeko.; Druz, Aliaksandr.; Asokan, Mangaiarkarasi.; Burton, Dennis R.; Connors, Mark.; Abdool Karim, Salim Safurdeen.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn.; Kwong, Peter D.; Morris, Lynn.; Moore, Penelope L.
Abstract available in pdf.
V2-directed vaccine-like antibodies from HIV-1 infection identify an additional K169-binding light chain motif with broad ADCC activity.
(Cell Press., 2018) van Eeden, Charmaine.; Wibmer, Constantinos Kurt.; Scheepers, Cathrine.; Richardson, Simone I.; Nonyane, Molati.; Lambson, Bronwen Elizabeth.; Mkhize, Nonhlanhla N.; Vijayakumar, Balakrishnan.; Sheng, Zizhang.; Stanfield-Oakley, Sherry.; Bhiman, Jinal N.; Bekker, Valerie.; Hermanus, Tandile.; Mabvakure, Batsirai.; Ismail, Arshad.; Moody, Michael Anthony.; Wiehe, Kevin.; Garrett, Nigel Joel.; Abdool Karim, Salim Safurdeen.; Dirr, Heini.; Fernandes, Manuel A.; Sayed, Yasien.; Shapiro, Lawrence.; Ferrari, Guido.; Haynes, Barton F.; Moore, Penelope L.; Morris, Lynn.
Abstract available in pdf.
Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes.
(Plos., 2013) Wibmer, Constantinos Kurt.; Bhiman, Jinal N.; Gray, Elin Solomonovna.; Tumba, Nancy Lola.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.; Morris, Lynn.; Moore, Penelope L.
Identifying the targets of broadly neutralizing antibodies to HIV-1 and understanding how these antibodies develop remain important goals in the quest to rationally develop an HIV-1 vaccine. We previously identified a participant in the CAPRISA Acute Infection Cohort (CAP257) whose plasma neutralized 84% of heterologous viruses. In this study we showed that breadth in CAP257 was largely due to the sequential, transient ppearance of three distinct broadly neutralizing antibody specificities spanning the first 4.5 years of infection. The first specificity targeted an epitope in the V2 region of gp120 that was also recognized by strain-specific antibodies 7 weeks earlier. Specificity for the autologous virus was determined largely by a rare N167 antigenic variant of V2, with viral escape to the more common D167 immunotype coinciding with the development of the first wave of broadly neutralizing antibodies. Escape from these broadly neutralizing V2 antibodies through deletion of the glycan at N160 was associated with exposure of an epitope in the CD4 binding site that became the target for a second wave of broadly neutralizing antibodies. Neutralization by these CD4 binding site antibodies was almost entirely dependent on the glycan at position N276. Early viral escape mutations in the CD4 binding site drove an increase in wave two neutralization breadth, as this second wave of heterologous neutralization matured to recognize multiple immunotypes within this site. The third wave targeted a quaternary epitope that did not overlap any of the four known sites of vulnerability on the HIV-1 envelope and remains undefined. Altogether this study showed that the human immune system is capable of generating multiple broadly neutralizing antibodies in response to a constantly evolving viral population that exposes new targets as a consequence of escape from earlier neutralizing antibodies.
Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies.
(Nature Publishing Group., 2015) Bhiman, Jinal N.; Anthony, Colin S.; Doria-Rose, Nicole A.; Karimanzira, Owen.; Schramm, Chaim A.; Khoza, Thandeka.; Kitchin, Dale.; Botha, Gordon.; Gorman, Jason.; Garrett, Nigel Joel.; Abdool Karim, Salim Safurdeen.; Shapiro, Lawrence.; Williamson, Carolyn.; Kwong, Peter D.; Mascola, John R.; Morris, Lynn.; Moore, Penelope L.
Abstract available in pdf.