Browsing by Author "Gorman, Jason."

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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.
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.
Ontogeny-based immunogens for the induction of V2-directed HIV broadly neutralizing antibodies.
(John Wiley & Sons., 2017) Moore, Penelope L.; Gorman, Jason.; Doria-Rose, Nicole A.; Morris, Lynn.
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.
Structure and immune recognition of trimeric pre-fusion HIV-1 Env.
(Macmillan Publishers Limited., 2014) Pancera, Marie.; Zhou, Tongqing.; Druz, Aliaksandr.; Georgiev, Ivelin S.; Soto, Cinque.; Gorman, Jason.; Huang, Jinghe.; Acharya, Priyamvada.; Chuang, Gwo-Yu.; Ofek, Gilad.; Stewart-Jones, Guillaume B. E.; Stuckey, Jonathan.; Bailer, Robert T.; Joyce, M. Gordon.; Louder, Mark K.; Tumba, Nancy Lola.; Yang, Yongping.; Zhang, Baoshan.; Cohen, Myron S.; Haynes, Barton F.; Mascola, John R.; Morris, Lynn.; Munro, James B.; Blanchard, Scott C.; Mothes, Walther.; Connors, Mark.; Kwong, Peter D.
The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.
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.
Structure of an N276-dependent HIV-1 neutralizing antibody targeting a rare V5 glycan hole adjacent to the CD4 binding site.
(American Society for Microbiology., 2016) Wibmer, Constantinos Kurt.; Gorman, Jason.; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr.; York, Talita.; Schmidt, Stephen D.; Labuschagne, Phillip.; Louder, Mark K.; Bailer, Robert T.; Abdool Karim, Salim Safurdeen.; Mascola, John R.; Williamson, Carolyn.; Moore, Penelope L.; Kwong, Peter D.; Morris, Lynn.
Abstract available in pdf.
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.