Browsing by Author "Berry, Madison"

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    Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.
    (NPJ vaccines, 2023-11) Nettere, Danielle; Unnithan, Shakthi; Rodgers, Nicole; Nohara, Junsuke; Cray, Paul; Berry, Madison; Jones, Caroline; Armand, Lawrence; Li, Shuk Hang; Berendam, Stella J; Fouda, Genevieve G; Cain, Derek W; Spence, Taylor N; Granek, Joshua A; Davenport, Clemontina A; Edwards, Robert J; Wiehe, Kevin; Van Rompay, Koen KA; Moody, M Anthony; Permar, Sallie R; Pollara, Justin
    An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env-HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg-Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines.
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    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 F
    Natural 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.
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    Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection.
    (Journal of virology, 2023-10) Evangelous, Tyler D; Berry, Madison; Venkatayogi, Sravani; LeMaster, Cas; Geanes, Eric S; De Naeyer, Nicole; DeMarco, Todd; Shen, Xiaoying; Li, Hui; Hora, Bhavna; Solomonis, Nicholas; Misamore, Johnathan; Lewis, Mark G; Denny, Thomas N; Montefiori, David; Shaw, George M; Wiehe, Kevin; Bradley, Todd; Williams, Wilton B
    We recently found that a new pathogenic chimeric simian-human immunodeficiency virus (SHIV) elicited heterologous human immunodeficiency virus type-1 (HIV-1) neutralizing antibodies (nAbs) in therapy-naïve young rhesus macaques (RMs) following neonatal SHIV infection. Moreover, a subset of the SHIV-infected young RMs spontaneously controlled viremia. Here we evaluated humoral and cellular immunity and plasma biomarkers associated with spontaneous viremia suppression in a new model of young SHIV-infected RMs that generated heterologous HIV-1 nAbs independent of viremia control to gain insights into pediatric immunity that may be harnessed by appropriate therapies in HIV-1-infected infants and children. We determined the levels of 31 plasma analytes (cytokines, chemokines, and growth factors) in SHIV-infected RMs over the course of infection and found that six analytes with chemoattractant or pro-inflammatory activities had significantly lower levels in plasma of RMs that controlled viremia compared to non-controllers. Single-cell transcriptomics of blood-derived immune cells demonstrated that RMs with viremia control had upregulated genes associated with immune activation and cytotoxic functions, whereas non-controllers had upregulated genes associated with immune cell exhaustion and dysfunction. In addition to CD8 T and natural killer cells, monocytes with upregulation of inhibitory genes previously reported only in cytotoxic cells constituted the immunologic environment associated with viremia suppression. These data implicated a complex immunologic milieu of viremia suppression that is not fully defined in pediatric subjects. Understanding immune cell subsets that may be harnessed to control viremia will provide insights into future designs of HIV-1 therapeutic strategies. IMPORTANCE Despite the advent of highly active anti-retroviral therapy, people are still dying from HIV-related causes, many of whom are children, and a protective vaccine or cure is needed to end the HIV pandemic. Understanding the nature and activation states of immune cell subsets during infection will provide insights into the immunologic milieu associated with viremia suppression that can be harnessed via therapeutic strategies to achieve a functional cure, but these are understudied in pediatric subjects. We evaluated humoral and adaptive host immunity associated with suppression of viremia in rhesus macaques infected soon after birth with a pathogenic SHIV. The results from our study provide insights into the immune cell subsets and functions associated with viremia control in young macaques that may translate to pediatric subjects for the design of future anti-viral strategies in HIV-1-infected infants and children and contribute to an understudied area of HIV-1 pathogenesis in pediatric subjects.
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    Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
    (Nature, 2021-06) Saunders, Kevin O; Lee, Esther; Parks, Robert; Martinez, David R; Li, Dapeng; Chen, Haiyan; Edwards, Robert J; Gobeil, Sophie; Barr, Maggie; Mansouri, Katayoun; Alam, S Munir; Sutherland, Laura L; Cai, Fangping; Sanzone, Aja M; Berry, Madison; Manne, Kartik; Bock, Kevin W; Minai, Mahnaz; Nagata, Bianca M; Kapingidza, Anyway B; Azoitei, Mihai; Tse, Longping V; Scobey, Trevor D; Spreng, Rachel L; Rountree, R Wes; DeMarco, C Todd; Denny, Thomas N; Woods, Christopher W; Petzold, Elizabeth W; Tang, Juanjie; Oguin, Thomas H; Sempowski, Gregory D; Gagne, Matthew; Douek, Daniel C; Tomai, Mark A; Fox, Christopher B; Seder, Robert; Wiehe, Kevin; Weissman, Drew; Pardi, Norbert; Golding, Hana; Khurana, Surender; Acharya, Priyamvada; Andersen, Hanne; Lewis, Mark G; Moore, Ian N; Montefiori, David C; Baric, Ralph S; Haynes, Barton F
    Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.
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    SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys.
    (bioRxiv, 2021-02-17) Saunders, Kevin O; Lee, Esther; Parks, Robert; Martinez, David R; Li, Dapeng; Chen, Haiyan; Edwards, Robert J; Gobeil, Sophie; Barr, Maggie; Mansouri, Katayoun; Alam, S Munir; Sutherland, Laura L; Cai, Fangping; Sanzone, Aja M; Berry, Madison; Manne, Kartik; Kapingidza, Anyway B; Azoitei, Mihai; Tse, Longping V; Scobey, Trevor D; Spreng, Rachel L; Rountree, R Wes; DeMarco, C Todd; Denny, Thomas N; Woods, Christopher W; Petzold, Elizabeth W; Oguin, Thomas H; Sempowski, Gregory D; Gagne, Matthew; Douek, Daniel C; Tomai, Mark A; Fox, Christopher B; Seder, Robert; Wiehe, Kevin; Weissman, Drew; Pardi, Norbert; Acharya, Priyamvada; Andersen, Hanne; Lewis, Mark G; Moore, Ian N; Montefiori, David C; Baric, Ralph S; Haynes, Barton F
    Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.