Browsing by Author "Tomaras, Georgia D."

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Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.
(Cell Press., 2014) Wiehe, Kevin.; Easterhoff, David.; Luo, Kan.; Nicely, Nathan I.; Bradley, Todd.; Jaeger, Frederick H.; Dennison, Sally Moses.; Zhang, Ruijun.; Lloyd, Krissey E.; Stolarchuk, Christina.; Parks, Robert.; Sutherland, Laura L.; Scearce, Richard M.; Morris, Lynn.; Kaewkungwal, Jaranit.; Nitayaphan, Sorachai.; Pitisuttithum, Punnee.; Rerks-Ngarm, Supachai.; Sinangil, Faruk.; Phogat, Sanjay.; Michael, Nelson L.; Kim, Jerome H.; Kelsoe, Garnett.; Montefiori, David Charles.; Tomaras, Georgia D.; Bonsignori, Mattia.; Santra, Sampa.; Kepler, Thomas B.; Alam, Shabnam Munir.; Moody, Michael Anthony.; Liao, Hua-Xin.; Haynes, Barton F.
Abstract available in pdf.
Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.
(Wolters Kluwer., 2016) Mkhize, Nonhlanhla N.; Durgiah, Raveshni.; Ashley, Vicki C.; Archary, Derseree.; Garrett, Nigel Joel.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Moore, Penelope L.; Yates, Nicole L.; Passmore, Jo-Ann Shelley.; Tomaras, Georgia D.; Morris, Lynn.
Abstract available in PDF file..
Computational analysis of antibody dynamics identifies recent HIV-1 infection.
(American Society for Clinical Investigation., 2017) Seaton, Kelly E.; Vandergrift, Nathan A.; Deal, Aaron W.; Rountree, Wes.; Bainbridge, John.; Grebe, Eduard.; Anderson, David A.; Sawant, Sheetal.; Shen, Xiaoying.; Yates, Nicole L.; Denny, Thomas N.; Liao, Hua-Xin.; Haynes, Barton F.; Robb, Merlin L.; Parkin, Neil.; Santos, Breno R.; Garrett, Nigel Joel.; Price, Matthew A.; Naniche, Denise.; Duerr, Ann C.; Keating, Sheila.; Hampton, Dylan.; Facente, Shelley.; Marson, Kara.; Welte, Alex.; Pilcher, Christopher D.; Cohen, Myron S.; Tomaras, Georgia D.
Abstract available in pdf.
The development of CD4 binding site antibodies during HIV-1 infection.
(American Society for Microbiology., 2012) Lynch, Rebecca M.; Tran, Lillian.; Louder, Mark K.; Schmidt, Stephen D.; Cohen, Myron S.; DerSimonian, Rebecca.; Euler, Zelda.; Gray, Elin Solomonovna.; Abdool Karim, Salim Safurdeen.; Kirchherr, Jennifer.; Montefiori, David Charles.; Sibeko, Sengeziwe.; Soderberg, Kelly.; Tomaras, Georgia D.; Yang, Zhi-Yong.; Nabel, Gary J.; Schuitemaker, Hanneke.; Morris, Lynn.; Haynes, Barton F.; Mascola, John R.
Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed the sera of 113 HIV-1 seroconverters from three cohorts for binding to a panel of gp120 core proteins and their corresponding CD4bs knockout mutants. Among sera collected between 99 and 258 weeks post-HIV-1 infection, 88% contained antibodies to the CD4bs and 47% contained antibodies to resurfaced stabilized core (RSC) probes that react preferentially with broadly neutralizing CD4bs antibodies (BNCD4), such as monoclonal antibodies (MAbs) VRC01 and VRC-CH31. Analysis of longitudinal serum samples from a subset of 18 subjects revealed that CD4bs antibodies to gp120 arose within the first 4 to 16 weeks of infection, while the development of RSC-reactive antibodies was more varied, occurring between 10 and 152 weeks post-HIV-1 infection. Despite the presence of these antibodies, serum neutralization mediated by RSC-reactive antibodies was detected in sera from only a few donors infected for more than 3 years. Thus, CD4bs antibodies that bind a VRC01-like epitope are often induced during HIV-1 infection, but the level and potency required to mediate serum neutralization may take years to develop. An improved understanding of the immunological factors associated with the development and maturation of neutralizing CD4bs antibodies during HIV-1 infection may provide insights into the requirements for eliciting this response by vaccination.
Distinct genital tract HIV-specific antibody profiles associated with Tenofovir gel.
(Nature., 2016) Archary, Derseree.; Seaton, Kelly E.; Passmore, Jo-Ann Shelley.; Werner, Lise.; Deal, Aaron W.; Dunphy, Laura J.; Arnold, Kelly B.; Yates, Nicole L.; Lauffenburger, Douglas A.; Bergin, Philip.; Liebenberg, Lenine Julie.; Samsunder, Natasha.; Mureithi, Marianne W.; Altfeld, Marcus.; Garrett, Nigel Joel.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Morris, Lynn.; Tomaras, Georgia D.
Abstract available in PDF file.
HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.
(Public Library of Science., 2014) Seaton, Kelly E.; Ballweber, Lamar.; Lan, Audrey.; Donathan, Michele.; Hughes, Sean.; Vojtech, Lucia.; Moody, Michael Anthony.; Liao, Hua-Xin.; Haynes, Barton F.; Galloway, Christine G.; Richardson, Barbra Ann.; Abdool Karim, Salim Safurdeen.; Dezzutti, Charlene S.; McElrath, Margaret Juliana.; Tomaras, Georgia D.; Hladik, Florian.
Abstract available in pdf.
Initial B-Cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.
(American Society for Microbiology., 2008) Tomaras, Georgia D.; Yates, Nicole L.; Liu, Pinghuang.; Qin, Li.; Fouda, Genevieve Giny.; Chavez, Leslie L.; Decamp, Allan C.; Parks, Robert J.; Ashley, Vicki C.; Lucas, Judith T.; Cohen, Myron S.; Eron, Joseph J.; Hick, Charles B.; Liao, Hua-Xin.; Self, Steven G.; Landucci, Gary.; Forthal, Donald N.; Weinhold, Kent J.; Keele, Brandon F.; Hahn, Beatrice H.; Greenberg, Michael L.; Morris, Lynn.; Abdool Karim, Salim Safurdeen.; Blattner, William A.; Montefiori, David Charles.; Shaw, George M.; Perelson, Alan S.; Haynes, Barton F.
A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.
Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.
(Plos., 2011) Morris, Lynn.; Chen, Xi.; Alam, Shabnam Munir.; Tomaras, Georgia D.; Zhang, Ruijun.; Marshall, Dawn J.; Chen, Bing.; Parks, Robert J.; Foulger, Andrew.; Jaeger, Frederick H.; Donathan, Michele.; Bilska, Mira.; Gray, Elin Solomonovna.; Abdool Karim, Salim Safurdeen.; Kepler, Thomas B.; Whitesides, John.; Montefiori, David Charles.; Moody, Michael Anthony.; Liao, Hua-Xin.; Haynes, Barton F.
Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.
Isolation of a Monoclonal Antibody That Targets the Alpha-2 Helix of gp120 and Represents the Initial Autologous Neutralizing-Antibody Response in an HIV-1 Subtype C-Infected Individual.
(American Society for Microbiology., 2011) Gray, Elin Solomonovna.; Moody, Michael Anthony.; Wibmer, Constantinos Kurt.; Chen, Xi.; Marshall, Dawn J.; Amos, Joshua.; Moore, Penelope L.; Foulger, Andrew.; Yu, Jae-Sung.; Lambson, Bronwen Elizabeth.; Abdool Karim, Salim Safurdeen.; Whitesides, John.; Tomaras, Georgia D.; Haynes, Barton F.; Morris, Lynn.; Liao, Hua-Xin.
The C3-V4 region is a major target of autologous neutralizing antibodies in HIV-1 subtype C infection. We previously identified a Center for AIDS Program of Research in South Africa (CAPRISA) participant, CAP88, who developed a potent neutralizing-antibody response within 3 months of infection that targeted an epitope in the C3 region of the HIV-1 envelope (P. L. Moore et al., PLoS Pathog. 5:e1000598, 2009). Here we showed that these type-specific antibodies could be adsorbed using recombinant gp120 from the transmitted/founder virus from CAP88 but not by gp120 made from other isolates. Furthermore, this activity could be depleted using a chimeric gp120 protein that contained only the C3 region from the CAP88 viral envelope engrafted onto the unrelated CAP63 viral envelope (called 63-88C3). On the basis of this, a differential sorting of memory B cells was performed using gp120s made from 63-88C3 and CAP63 labeled with different fluorochromes as positive and negative probes, respectively. This strategy resulted in the isolation of a highly specific monoclonal antibody (MAb), called CAP88-CH06, that neutralized the CAP88 transmitted/founder virus and viruses from acute infection but was unable to neutralize CAP88 viruses isolated at 6 and 12 months postinfection. The latter viruses contained 2 amino acid changes in the alpha-2 helix of C3 that mediated escape from this MAb. One of these changes involved the introduction of an N-linked glycan at position 339 that occluded the epitope, while the other mutation (either E343K or E350K) was a charge change. Our data validate the use of differential sorting to isolate a MAb targeting a specific epitope in the envelope glycoprotein and provided insights into the mechanisms of autologous neutralization escape.
Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.
(American Association for the Advancement of Science., 2017) Williams, LaTonya D.; Ofek, Gilad.; Schätzle, Sebastian.; McDaniel, Jonathan R.; Lu, Xiaozhi.; Nicely, Nathan I.; Wu, Liming; Lougheed, Caleb S.; Bradley, Todd.; Louder, Mark K.; McKee, Krisha.; Bailer, Robert T.; O’Dell, Sijy.; Georgiev, Ivelin S.; Seaman, Michael S.; Parks, Robert J.; Marshall, Dawn J.; Anasti, Kara.; Yang, Guang.; Nie, Xiaoyan.; Tumba, Nancy Lola.; Wiehe, Kevin.; Wagh, Kshitij.; Korber, Bette T. M.; Kepler, Thomas B.; Alam, Shabnam Munir.; Morris, Lynn.; Kamanga, Gift.; Cohen, Myron S.; Bonsignori, Mattia.; Xia, Shi-Mao.; Montefiori, David Charles.; Kelsoe, Garnett.; Gao, Feng.; Mascola, John R.; Moody, Michael Anthony.; Saunders, Kevin O.; Liao, Hua-Xin.; Tomaras, Georgia D.; Georgiou, George.; Haynes, Barton F.
Abstract available in pdf.