Browsing by Author "McMahan, Katherine"

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    A genetically engineered, stem-cell-derived cellular vaccine.
    (Cell reports. Medicine, 2022-12) Cooper, Amanda; Sidaway, Adam; Chandrashekar, Abishek; Latta, Elizabeth; Chakraborty, Krishnendu; Yu, Jingyou; McMahan, Katherine; Giffin, Victoria; Manickam, Cordelia; Kroll, Kyle; Mosher, Matthew; Reeves, R Keith; Gam, Rihab; Arthofer, Elisa; Choudhry, Modassir; Henley, Tom; Barouch, Dan H
    Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.
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    Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.
    (Nature, 2020-10) Mercado, Noe B; Zahn, Roland; Wegmann, Frank; Loos, Carolin; Chandrashekar, Abishek; Yu, Jingyou; Liu, Jinyan; Peter, Lauren; McMahan, Katherine; Tostanoski, Lisa H; He, Xuan; Martinez, David R; Rutten, Lucy; Bos, Rinke; van Manen, Danielle; Vellinga, Jort; Custers, Jerome; Langedijk, Johannes P; Kwaks, Ted; Bakkers, Mark JG; Zuijdgeest, David; Rosendahl Huber, Sietske K; Atyeo, Caroline; Fischinger, Stephanie; Burke, John S; Feldman, Jared; Hauser, Blake M; Caradonna, Timothy M; Bondzie, Esther A; Dagotto, Gabriel; Gebre, Makda S; Hoffman, Emily; Jacob-Dolan, Catherine; Kirilova, Marinela; Li, Zhenfeng; Lin, Zijin; Mahrokhian, Shant H; Maxfield, Lori F; Nampanya, Felix; Nityanandam, Ramya; Nkolola, Joseph P; Patel, Shivani; Ventura, John D; Verrington, Kaylee; Wan, Huahua; Pessaint, Laurent; Van Ry, Alex; Blade, Kelvin; Strasbaugh, Amanda; Cabus, Mehtap; Brown, Renita; Cook, Anthony; Zouantchangadou, Serge; Teow, Elyse; Andersen, Hanne; Lewis, Mark G; Cai, Yongfei; Chen, Bing; Schmidt, Aaron G; Reeves, R Keith; Baric, Ralph S; Lauffenburger, Douglas A; Alter, Galit; Stoffels, Paul; Mammen, Mathai; Van Hoof, Johan; Schuitemaker, Hanneke; Barouch, Dan H
    A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1-8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.