Browsing by Author "Parks, Robert J."

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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.
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.