Browsing by Author "Parks, Robert J"
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Item Open Access Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.(Cell, 2021-05-18) Williams, Wilton B; Meyerhoff, R Ryan; Edwards, RJ; Li, Hui; Manne, Kartik; Nicely, Nathan I; Henderson, Rory; Zhou, Ye; Janowska, Katarzyna; Mansouri, Katayoun; Gobeil, Sophie; Evangelous, Tyler; Hora, Bhavna; Berry, Madison; Abuahmad, A Yousef; Sprenz, Jordan; Deyton, Margaret; Stalls, Victoria; Kopp, Megan; Hsu, Allen L; Borgnia, Mario J; Stewart-Jones, Guillaume BE; Lee, Matthew S; Bronkema, Naomi; Moody, M Anthony; Wiehe, Kevin; Bradley, Todd; Alam, S Munir; Parks, Robert J; Foulger, Andrew; Oguin, Thomas; Sempowski, Gregory D; Bonsignori, Mattia; LaBranche, Celia C; Montefiori, David C; Seaman, Michael; Santra, Sampa; Perfect, John; Francica, Joseph R; Lynn, Geoffrey M; Aussedat, Baptiste; Walkowicz, William E; Laga, Richard; Kelsoe, Garnett; Saunders, Kevin O; Fera, Daniela; Kwong, Peter D; Seder, Robert A; Bartesaghi, Alberto; Shaw, George M; Acharya, Priyamvada; Haynes, Barton FNatural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.Item Open Access Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization.(Cell reports, 2020-02) Han, Qifeng; Bradley, Todd; Williams, Wilton B; Cain, Derek W; Montefiori, David C; Saunders, Kevin O; Parks, Robert J; Edwards, Regina W; Ferrari, Guido; Mueller, Olaf; Shen, Xiaoying; Wiehe, Kevin J; Reed, Steven; Fox, Christopher B; Rountree, Wes; Vandergrift, Nathan A; Wang, Yunfei; Sutherland, Laura L; Santra, Sampa; Moody, M Anthony; Permar, Sallie R; Tomaras, Georgia D; Lewis, Mark G; Van Rompay, Koen KA; Haynes, Barton FHIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination reveal that neonatal macaques have higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive interleukin-10 (IL-10) receptor alpha (IL10RA) mRNA transcripts in T cells, B cells, natural killer (NK) cells, and monocytes. In addition, immunized neonatal macaques exhibit increased frequencies of activated blood T follicular helper-like (Tfh) cells compared to adults. Thus, neonatal macaques have transcriptome signatures of decreased immunosuppression and apoptosis compared with adult macaques, providing an immune landscape conducive to early-life immunization prior to sexual debut.Item Open Access Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.(J Virol, 2012-04) Bonsignori, Mattia; Montefiori, David C; Wu, Xueling; Chen, Xi; Hwang, Kwan-Ki; Tsao, Chun-Yen; Kozink, Daniel M; Parks, Robert J; Tomaras, Georgia D; Crump, John A; Kapiga, Saidi H; Sam, Noel E; Kwong, Peter D; Kepler, Thomas B; Liao, Hua-Xin; Mascola, John R; Haynes, Barton FPlasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.