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3. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Author

Tostanoski, Lisa H., Wegmann, Frank, Martinot, Amanda J., Loos, Carolin, McMahan, Katherine, Mercado, Noe B., Yu, Jingyou, Chan, Chi N., Bondoc, Stephen, Starke, Carly E., Nekorchuk, Michael, Busman-Sahay, Kathleen, Piedra-Mora, Cesar, Wrijil, Linda M., Ducat, Sarah, Custers, Jerome, Atyeo, Caroline, Fischinger, Stephanie, Burke, John S., Feldman, Jared, Hauser, Blake M., Caradonna, Timothy M., Bondzie, Esther A., Dagotto, Gabriel, Gebre, Makda S., Jacob-Dolan, Catherine, Lin, Zijin, Mahrokhian, Shant H., Nampanya, Felix, Nityanandam, Ramya, Pessaint, Laurent, Porto, Maciel, Ali, Vaneesha, Benetiene, Dalia, Tevi, Komlan, Andersen, Hanne, Lewis, Mark G., Schmidt, Aaron G., Lauffenburger, Douglas A., Alter, Galit, Estes, Jacob D., Schuitemaker, Hanneke, Zahn, Roland, and Barouch, Dan H.

Published
2020
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4. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Author

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 J. G., 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, and Barouch, Dan H.

Published
2020
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6. Publisher Correction: Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Author

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 J. G., Zuijdgeest, David, Huber, Sietske K. Rosendahl, 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, and Barouch, Dan H.

Published
2021
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10. Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2

Author

Tostanoski, Lisa H., primary, Gralinski, Lisa E., additional, Martinez, David R., additional, Schaefer, Alexandra, additional, Mahrokhian, Shant H., additional, Li, Zhenfeng, additional, Nampanya, Felix, additional, Wan, Huahua, additional, Yu, Jingyou, additional, Chang, Aiquan, additional, Liu, Jinyan, additional, McMahan, Katherine, additional, Ventura, John D., additional, Dinnon, Kenneth H., additional, Leist, Sarah R., additional, Baric, Ralph S., additional, and Barouch, Dan H., additional

Published
2021
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11. Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern

Author

Tostanoski, Lisa H., primary, Yu, Jingyou, additional, Mercado, Noe B., additional, McMahan, Katherine, additional, Jacob-Dolan, Catherine, additional, Martinot, Amanda J., additional, Piedra-Mora, Cesar, additional, Anioke, Tochi, additional, Chang, Aiquan, additional, Giffin, Victoria M., additional, Hope, David L., additional, Wan, Huahua, additional, Bondzie, Esther A., additional, Mahrokhian, Shant H., additional, Wrijil, Linda M., additional, Bauer, Katherine, additional, Pessaint, Laurent, additional, Porto, Maciel, additional, Piegols, Joseph, additional, Faudree, Andrew, additional, Spence, Brittany, additional, Kar, Swagata, additional, Amanat, Fatima, additional, Krammer, Florian, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, Wegmann, Frank, additional, Zahn, Roland, additional, Schuitemaker, Hanneke, additional, and Barouch, Dan H., additional

Published
2021
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13. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Author

Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, 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 J. G., Zuijdgeest, David, Rosendahl Huber, Sietske K., Atyeo, Caroline, Fischinger, Stephanie, Burke, John, Feldman, Jared, Hauser, Blake Marie, 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, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, 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 J. G., Zuijdgeest, David, Rosendahl Huber, Sietske K., Atyeo, Caroline, Fischinger, Stephanie, Burke, John, Feldman, Jared, Hauser, Blake Marie, 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, and Barouch, Dan

Abstract

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.

Published
2021

16. Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Tostanoski, Lisa H., Wegmann, Frank, Martinot, Amanda J., Loos, Carolin, McMahan, Katherine, Mercado, Noe B., Yu, Jingyou, Chan, Chi N., Bondoc, Stephen, Starke, Carly E., Nekorchuk, Michael, Busman-Sahay, Kathleen, Piedra-Mora, Cesar, Wrijil, Linda M., Ducat, Sarah, Custers, Jerome, Atyeo, Caroline, Fischinger, Stephanie, Burke, John S., Feldman, Jared, Hauser, Blake M., Caradonna, Timothy M., Bondzie, Esther A., Dagotto, Gabriel, Gebre, Makda S., Jacob-Dolan, Catherine, Lin, Zijin, Mahrokhian, Shant H., Nampanya, Felix, Nityanandam, Ramya, Pessaint, Laurent, Porto, Maciel, Ali, Vaneesha, Benetiene, Dalia, Tevi, Komlan, Andersen, Hanne, Lewis, Mark G., Schmidt, Aaron G., Lauffenburger, Douglas A, Alter, Galit, Estes, Jacob D., Schuitemaker, Hanneke, Zahn, Roland, Barouch, Dan H., Massachusetts Institute of Technology. Department of Biological Engineering, Tostanoski, Lisa H., Wegmann, Frank, Martinot, Amanda J., Loos, Carolin, McMahan, Katherine, Mercado, Noe B., Yu, Jingyou, Chan, Chi N., Bondoc, Stephen, Starke, Carly E., Nekorchuk, Michael, Busman-Sahay, Kathleen, Piedra-Mora, Cesar, Wrijil, Linda M., Ducat, Sarah, Custers, Jerome, Atyeo, Caroline, Fischinger, Stephanie, Burke, John S., Feldman, Jared, Hauser, Blake M., Caradonna, Timothy M., Bondzie, Esther A., Dagotto, Gabriel, Gebre, Makda S., Jacob-Dolan, Catherine, Lin, Zijin, Mahrokhian, Shant H., Nampanya, Felix, Nityanandam, Ramya, Pessaint, Laurent, Porto, Maciel, Ali, Vaneesha, Benetiene, Dalia, Tevi, Komlan, Andersen, Hanne, Lewis, Mark G., Schmidt, Aaron G., Lauffenburger, Douglas A, Alter, Galit, Estes, Jacob D., Schuitemaker, Hanneke, Zahn, Roland, and Barouch, Dan H.

Abstract

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters and nonhuman primates have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

Published
2020

17. Protective efficacy of an attenuated Mtb ΔLprG vaccine in mice

Author

Martinot, Amanda J., primary, Blass, Eryn, additional, Yu, Jingyou, additional, Aid, Malika, additional, Mahrokhian, Shant H., additional, Cohen, Sara B., additional, Plumlee, Courtney R., additional, Larocca, Rafael A., additional, Siddiqi, Noman, additional, Wakabayashi, Shoko, additional, Gardner, Michelle, additional, Audette, Rebecca, additional, Devorak, Anne, additional, Urdahl, Kevin B., additional, Rubin, Eric J., additional, and Barouch, Dan H., additional

Published
2020
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18. DNA vaccine protection against SARS-CoV-2 in rhesus macaques

Author

Yu, Jingyou, primary, Tostanoski, Lisa H., additional, Peter, Lauren, additional, Mercado, Noe B., additional, McMahan, Katherine, additional, Mahrokhian, Shant H., additional, Nkolola, Joseph P., additional, Liu, Jinyan, additional, Li, Zhenfeng, additional, Chandrashekar, Abishek, additional, Martinez, David R., additional, Loos, Carolin, additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Burke, John S., additional, Slein, Matthew D., additional, Chen, Yuezhou, additional, Zuiani, Adam, additional, Lelis, Felipe J. N., additional, Travers, Meghan, additional, Habibi, Shaghayegh, additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Blade, Kelvin, additional, Brown, Renita, additional, Cook, Anthony, additional, Finneyfrock, Brad, additional, Dodson, Alan, additional, Teow, Elyse, additional, Velasco, Jason, additional, Zahn, Roland, additional, Wegmann, Frank, additional, Bondzie, Esther A., additional, Dagotto, Gabriel, additional, Gebre, Makda S., additional, He, Xuan, additional, Jacob-Dolan, Catherine, additional, Kirilova, Marinela, additional, Kordana, Nicole, additional, Lin, Zijin, additional, Maxfield, Lori F., additional, Nampanya, Felix, additional, Nityanandam, Ramya, additional, Ventura, John D., additional, Wan, Huahua, additional, Cai, Yongfei, additional, Chen, Bing, additional, Schmidt, Aaron G., additional, Wesemann, Duane R., additional, Baric, Ralph S., additional, Alter, Galit, additional, Andersen, Hanne, additional, Lewis, Mark G., additional, and Barouch, Dan H., additional

Published
2020
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19. SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Author

Chandrashekar, Abishek, primary, Liu, Jinyan, additional, Martinot, Amanda J., additional, McMahan, Katherine, additional, Mercado, Noe B., additional, Peter, Lauren, additional, Tostanoski, Lisa H., additional, Yu, Jingyou, additional, Maliga, Zoltan, additional, Nekorchuk, Michael, additional, Busman-Sahay, Kathleen, additional, Terry, Margaret, additional, Wrijil, Linda M., additional, Ducat, Sarah, additional, Martinez, David R., additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Burke, John S., additional, Slein, Matthew D., additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Greenhouse, Jack, additional, Taylor, Tammy, additional, Blade, Kelvin, additional, Cook, Anthony, additional, Finneyfrock, Brad, additional, Brown, Renita, additional, Teow, Elyse, additional, Velasco, Jason, additional, Zahn, Roland, additional, Wegmann, Frank, additional, Abbink, Peter, additional, Bondzie, Esther A., additional, Dagotto, Gabriel, additional, Gebre, Makda S., additional, He, Xuan, additional, Jacob-Dolan, Catherine, additional, Kordana, Nicole, additional, Li, Zhenfeng, additional, Lifton, Michelle A., additional, Mahrokhian, Shant H., additional, Maxfield, Lori F., additional, Nityanandam, Ramya, additional, Nkolola, Joseph P., additional, Schmidt, Aaron G., additional, Miller, Andrew D., additional, Baric, Ralph S., additional, Alter, Galit, additional, Sorger, Peter K., additional, Estes, Jacob D., additional, Andersen, Hanne, additional, Lewis, Mark G., additional, and Barouch, Dan H., additional

Published
2020
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20. Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

Author

Tostanoski LH, Gralinski LE, Martinez DR, Schaefer A, Mahrokhian SH, Li Z, Nampanya F, Wan H, Yu J, Chang A, Liu J, McMahan K, Dinnon KH, Leist SR, Baric RS, and Barouch DH

Abstract

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice., Importance: We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

Published
2021
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