Browsing by Author "Jiang, Chuancang"

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    Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.
    (Nature communications, 2017-11-23) Williams, Wilton B; Zhang, Jinsong; Jiang, Chuancang; Nicely, Nathan I; Fera, Daniela; Luo, Kan; Moody, M Anthony; Liao, Hua-Xin; Alam, S Munir; Kepler, Thomas B; Ramesh, Akshaya; Wiehe, Kevin; Holland, James A; Bradley, Todd; Vandergrift, Nathan; Saunders, Kevin O; Parks, Robert; Foulger, Andrew; Xia, Shi-Mao; Bonsignori, Mattia; Montefiori, David C; Louder, Mark; Eaton, Amanda; Santra, Sampa; Scearce, Richard; Sutherland, Laura; Newman, Amanda; Bouton-Verville, Hilary; Bowman, Cindy; Bomze, Howard; Gao, Feng; Marshall, Dawn J; Whitesides, John F; Nie, Xiaoyan; Kelsoe, Garnett; Reed, Steven G; Fox, Christopher B; Clary, Kim; Koutsoukos, Marguerite; Franco, David; Mascola, John R; Harrison, Stephen C; Haynes, Barton F; Verkoczy, Laurent
    A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env+ (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.
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    The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.
    (bioRxiv, 2021-02-18) Li, Dapeng; Edwards, Robert J; Manne, Kartik; Martinez, David R; Schäfer, Alexandra; Alam, S Munir; Wiehe, Kevin; Lu, Xiaozhi; Parks, Robert; Sutherland, Laura L; Oguin, Thomas H; McDanal, Charlene; Perez, Lautaro G; Mansouri, Katayoun; Gobeil, Sophie MC; Janowska, Katarzyna; Stalls, Victoria; Kopp, Megan; Cai, Fangping; Lee, Esther; Foulger, Andrew; Hernandez, Giovanna E; Sanzone, Aja; Tilahun, Kedamawit; Jiang, Chuancang; Tse, Longping V; Bock, Kevin W; Minai, Mahnaz; Nagata, Bianca M; Cronin, Kenneth; Gee-Lai, Victoria; Deyton, Margaret; Barr, Maggie; Holle, Tarra Von; Macintyre, Andrew N; Stover, Erica; Feldman, Jared; Hauser, Blake M; Caradonna, Timothy M; Scobey, Trevor D; Rountree, Wes; Wang, Yunfei; Moody, M Anthony; Cain, Derek W; DeMarco, C Todd; Denny, ThomasN; Woods, Christopher W; Petzold, Elizabeth W; Schmidt, Aaron G; Teng, I-Ting; Zhou, Tongqing; Kwong, Peter D; Mascola, John R; Graham, Barney S; Moore, Ian N; Seder, Robert; Andersen, Hanne; Lewis, Mark G; Montefiori, David C; Sempowski, Gregory D; Baric, Ralph S; Acharya, Priyamvada; Haynes, Barton F; Saunders, Kevin O
    SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro , while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.