Search

Your search keyword '"Donaldson, Mitzi M."' showing total 19 results
Start Over Author "Donaldson, Mitzi M."
19 results on '"Donaldson, Mitzi M."'

2. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Author

Stanley, Daphne A., Honko, Anna N., Asiedu, Clement, Trefry, John C., Lau-Kilby, Annie W., Johnson, Joshua C., Hensley, Lisa, Ammendola, Virginia, Abbate, Adele, Grazioli, Fabiana, Foulds, Kathryn E., Cheng, Cheng, Wang, Lingshu, Donaldson, Mitzi M., Colloca, Stefano, Folgori, Antonella, Roederer, Mario, Nabel, Gary J., Mascola, John, Nicosia, Alfredo, Cortese, Riccardo, Koup, Richard A., and Sullivan, Nancy J.

Subjects
Viral vaccines -- Research -- Analysis -- Physiological aspects, Ebola virus -- Research -- Analysis, Biological sciences, Health
Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge., Human-derived rAd vectors have undergone extensive development in preclinical and human trials as vaccines for multiple pathogens (1-6). For ebolavirus, rAd vaccines that confer protection against acute EBOV challenge generate [...]

Published
2014
Full Text
View/download PDF

3. Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine–boosted nonhuman primates

Author

Corbett, Kizzmekia S., primary, Gagne, Matthew, additional, Wagner, Danielle A., additional, O’ Connell, Sarah, additional, Narpala, Sandeep R., additional, Flebbe, Dillon R., additional, Andrew, Shayne F., additional, Davis, Rachel L., additional, Flynn, Barbara, additional, Johnston, Timothy S., additional, Stringham, Christopher D., additional, Lai, Lilin, additional, Valentin, Daniel, additional, Van Ry, Alex, additional, Flinchbaugh, Zackery, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Sriparna, Manjari, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Tucker, Courtney, additional, Choi, Angela, additional, Koch, Matthew, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Alvarado, Gabriela S., additional, Henry, Amy R., additional, Laboune, Farida, additional, Schramm, Chaim A., additional, Zhang, Yi, additional, Yang, Eun Sung, additional, Wang, Lingshu, additional, Choe, Misook, additional, Boyoglu-Barnum, Seyhan, additional, Wei, Shi, additional, Lamb, Evan, additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Donaldson, Mitzi M., additional, Marquez, Josue, additional, Todd, John-Paul M., additional, Cook, Anthony, additional, Dodson, Alan, additional, Pekosz, Andrew, additional, Boritz, Eli, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Pessaint, Laurent, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Misasi, John, additional, Wu, Kai, additional, Carfi, Andrea, additional, Nason, Martha C., additional, Mascola, John, additional, Moore, Ian N., additional, Edwards, Darin K., additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Roederer, Mario, additional, McDermott, Adrian, additional, Douek, Daniel C., additional, Sullivan, Nancy J., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

4. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Author

Corbett, Kizzmekia S., primary, Nason, Martha C., additional, Flach, Britta, additional, Gagne, Matthew, additional, O’Connell, Sarah, additional, Johnston, Timothy S., additional, Shah, Shruti N., additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, McDanal, Charlene, additional, Francica, Joseph R., additional, Flynn, Barbara, additional, Wu, Kai, additional, Choi, Angela, additional, Koch, Matthew, additional, Abiona, Olubukola M., additional, Werner, Anne P., additional, Moliva, Juan I., additional, Andrew, Shayne F., additional, Donaldson, Mitzi M., additional, Fintzi, Jonathan, additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Noe, Amy T., additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Cook, Anthony, additional, Dodson, Alan, additional, Faudree, Andrew, additional, Greenhouse, Jack, additional, Kar, Swagata, additional, Pessaint, Laurent, additional, Porto, Maciel, additional, Steingrebe, Katelyn, additional, Valentin, Daniel, additional, Zouantcha, Serge, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, van de Wetering, Renee, additional, Boyoglu-Barnum, Seyhan, additional, Leung, Kwanyee, additional, Shi, Wei, additional, Yang, Eun Sung, additional, Zhang, Yi, additional, Todd, John-Paul M., additional, Wang, Lingshu, additional, Alvarado, Gabriela S., additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Edwards, Darin K., additional, Mascola, John R., additional, Moore, Ian N., additional, Lewis, Mark G., additional, Carfi, Andrea, additional, Montefiori, David, additional, Suthar, Mehul S., additional, McDermott, Adrian, additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

5. Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates

Author

Francica, Joseph R., primary, Flynn, Barbara J., additional, Foulds, Kathryn E., additional, Noe, Amy T., additional, Werner, Anne P., additional, Moore, Ian N., additional, Gagne, Matthew, additional, Johnston, Timothy S., additional, Tucker, Courtney, additional, Davis, Rachel L., additional, Flach, Britta, additional, O’Connell, Sarah, additional, Andrew, Shayne F., additional, Lamb, Evan, additional, Flebbe, Dillon R., additional, Nurmukhambetova, Saule T., additional, Donaldson, Mitzi M., additional, Todd, John-Paul M., additional, Zhu, Alex Lee, additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Gorman, Matthew J, additional, Shin, Sally, additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, Boyoglu-Barnum, Seyhan, additional, Van De Wetering, Renee, additional, Tylor, Alida, additional, McCarthy, Elizabeth, additional, Lecouturier, Valerie, additional, Ruiz, Sophie, additional, Berry, Catherine, additional, Tibbitts, Timothy, additional, Andersen, Hanne, additional, Cook, Anthony, additional, Dodson, Alan, additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Koutsoukos, Marguerite, additional, Gutzeit, Cindy, additional, Teng, I.-Ting, additional, Zhou, Tongqing, additional, Li, Dapeng, additional, Haynes, Barton F., additional, Kwong, Peter D., additional, McDermott, Adrian, additional, Lewis, Mark G., additional, Fu, Tong Ming, additional, Chicz, Roman, additional, van der Most, Robbert, additional, Corbett, Kizzmekia S., additional, Suthar, Mehul S., additional, Alter, Galit, additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Graham, Barney S., additional, Casimiro, Danilo, additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

6. Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Gagne, Matthew, additional, Wagner, Danielle A., additional, Connell, Sarah O’, additional, Narpala, Sandeep R., additional, Flebbe, Dillon R., additional, Andrew, Shayne F., additional, Davis, Rachel L., additional, Flynn, Barbara, additional, Johnston, Timothy S., additional, Stringham, Christopher, additional, Lai, Lilin, additional, Valentin, Daniel, additional, Van Ry, Alex, additional, Flinchbaugh, Zackery, additional, Werner, Anne P., additional, Moliva, Juan I., additional, Sriparna, Manjari, additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Tucker, Courtney, additional, Choi, Angela, additional, Koch, Matthew, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Alvarado, Gabriela S., additional, Henry, Amy R., additional, Laboune, Farida, additional, Schramm, Chaim A., additional, Zhang, Yi, additional, Wang, Lingshu, additional, Choe, Misook, additional, Boyoglu-Barnum, Seyhan, additional, Shi, Wei, additional, Lamb, Evan, additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Donaldson, Mitzi M., additional, Marquez, Josue, additional, Todd, John-Paul M., additional, Cook, Anthony, additional, Dodson, Alan, additional, Pekosz, Andrew, additional, Boritz, Eli, additional, Ploquin, Aurélie, additional, Doria-Rose, Nicole, additional, Pessaint, Laurent, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Misasi, John, additional, Wu, Kai, additional, Carfi, Andrea, additional, Nason, Martha C., additional, Mascola, John, additional, Moore, Ian N., additional, Edwards, Darin K., additional, Lewis, Mark G., additional, Suthar, Mehul S., additional, Roederer, Mario, additional, McDermott, Adrian, additional, Douek, Daniel C., additional, Sullivan, Nancy J., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

7. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Nason, Martha C., additional, Flach, Britta, additional, Gagne, Matthew, additional, O’ Connell, Sarah, additional, Johnston, Timothy S., additional, Shah, Shruti N., additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, McDanal, Charlene, additional, Francica, Joseph R., additional, Flynn, Barbara, additional, Wu, Kai, additional, Choi, Angela, additional, Koch, Matthew, additional, Abiona, Olubukola M., additional, Werner, Anne P., additional, Alvarado, Gabriela S., additional, Andrew, Shayne F., additional, Donaldson, Mitzi M., additional, Fintzi, Jonathan, additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Noe, Amy T., additional, Nurmukhambetova, Saule T., additional, Provost, Samantha J., additional, Cook, Anthony, additional, Dodson, Alan, additional, Faudree, Andrew, additional, Greenhouse, Jack, additional, Kar, Swagata, additional, Pessaint, Laurent, additional, Porto, Maciel, additional, Steingrebe, Katelyn, additional, Valentin, Daniel, additional, Zouantcha, Serge, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Moliva, Juan I., additional, van de Wetering, Renee, additional, Boyoglu-Barnum, Seyhan, additional, Leung, Kwanyee, additional, Shi, Wei, additional, Yang, Eun Sung, additional, Zhang, Yi, additional, Todd, John-Paul M., additional, Wang, Lingshu, additional, Andersen, Hanne, additional, Foulds, Kathryn E., additional, Edwards, Darin K., additional, Mascola, John R., additional, Moore, Ian N., additional, Lewis, Mark G., additional, Carfi, Andrea, additional, Montefiori, David, additional, Suthar, Mehul S., additional, McDermott, Adrian, additional, Sullivan, Nancy J., additional, Roederer, Mario, additional, Douek, Daniel C., additional, Graham, Barney S., additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

8. Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates

Author

Marcus, Hadar, primary, Thompson, Emily, additional, Zhou, Yan, additional, Bailey, Michael, additional, Donaldson, Mitzi M., additional, Stanley, Daphne A., additional, Asiedu, Clement, additional, Foulds, Kathryn E., additional, Roederer, Mario, additional, Moliva, Juan I., additional, and Sullivan, Nancy J., additional

Published
2021
Full Text
View/download PDF

9. Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates

Author

Francica, Joseph R., primary, Flynn, Barbara J., additional, Foulds, Kathryn E., additional, Noe, Amy T., additional, Werner, Anne P., additional, Moore, Ian N., additional, Gagne, Matthew, additional, Johnston, Timothy S., additional, Tucker, Courtney, additional, Davis, Rachel L., additional, Flach, Britta, additional, O’Connell, Sarah, additional, Andrew, Shayne F., additional, Lamb, Evan, additional, Flebbe, Dillon R., additional, Nurmukhambetova, Saule T., additional, Donaldson, Mitzi M., additional, Todd, John-Paul M., additional, Zhu, Alex Lee, additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Gorman, Matthew J, additional, Shin, Sally, additional, Edara, Venkata Viswanadh, additional, Floyd, Katharine, additional, Lai, Lilin, additional, Tylor, Alida, additional, McCarthy, Elizabeth, additional, Lecouturier, Valerie, additional, Ruiz, Sophie, additional, Berry, Catherine, additional, Tibbitts, Timothy, additional, Andersen, Hanne, additional, Cook, Anthony, additional, Dodson, Alan, additional, Pessaint, Laurent, additional, Ry, Alex Van, additional, Koutsoukos, Marguerite, additional, Gutzeit, Cindy, additional, Teng, I-Ting, additional, Zhou, Tongqing, additional, Li, Dapeng, additional, Haynes, Barton F., additional, Kwong, Peter D., additional, McDermott, Adrian, additional, Lewis, Mark G., additional, Fu, Tong Ming, additional, Chicz, Roman, additional, van der Most, Robbert, additional, Corbett, Kizzmekia S., additional, Suthar, Mehul S., additional, Alter, Galit, additional, Roederer, Mario, additional, Sullivan, Nancy J., additional, Douek, Daniel C., additional, Graham, Barney S., additional, Casimiro, Danilo, additional, and Seder, Robert A., additional

Published
2021
Full Text
View/download PDF

11. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Author

Corbett, Kizzmekia S., primary, Flynn, Barbara, additional, Foulds, Kathryn E., additional, Francica, Joseph R., additional, Boyoglu-Barnum, Seyhan, additional, Werner, Anne P., additional, Flach, Britta, additional, O’Connell, Sarah, additional, Bock, Kevin W., additional, Minai, Mahnaz, additional, Nagata, Bianca M., additional, Andersen, Hanne, additional, Martinez, David R., additional, Noe, Amy T., additional, Douek, Naomi, additional, Donaldson, Mitzi M., additional, Nji, Nadesh N., additional, Alvarado, Gabriela S., additional, Edwards, Darin K., additional, Flebbe, Dillon R., additional, Lamb, Evan, additional, Doria-Rose, Nicole A., additional, Lin, Bob C., additional, Louder, Mark K., additional, O’Dell, Sijy, additional, Schmidt, Stephen D., additional, Phung, Emily, additional, Chang, Lauren A., additional, Yap, Christina, additional, Todd, John-Paul M., additional, Pessaint, Laurent, additional, Van Ry, Alex, additional, Browne, Shanai, additional, Greenhouse, Jack, additional, Putman-Taylor, Tammy, additional, Strasbaugh, Amanda, additional, Campbell, Tracey-Ann, additional, Cook, Anthony, additional, Dodson, Alan, additional, Steingrebe, Katelyn, additional, Shi, Wei, additional, Zhang, Yi, additional, Abiona, Olubukola M., additional, Wang, Lingshu, additional, Pegu, Amarendra, additional, Yang, Eun Sung, additional, Leung, Kwanyee, additional, Zhou, Tongqing, additional, Teng, I-Ting, additional, Widge, Alicia, additional, Gordon, Ingelise, additional, Novik, Laura, additional, Gillespie, Rebecca A., additional, Loomis, Rebecca J., additional, Moliva, Juan I., additional, Stewart-Jones, Guillaume, additional, Himansu, Sunny, additional, Kong, Wing-Pui, additional, Nason, Martha C., additional, Morabito, Kaitlyn M., additional, Ruckwardt, Tracy J., additional, Ledgerwood, Julie E., additional, Gaudinski, Martin R., additional, Kwong, Peter D., additional, Mascola, John R., additional, Carfi, Andrea, additional, Lewis, Mark G., additional, Baric, Ralph S., additional, McDermott, Adrian, additional, Moore, Ian N., additional, Sullivan, Nancy J., additional, Roederer, Mario, additional, Seder, Robert A., additional, and Graham, Barney S., additional

Published
2020
Full Text
View/download PDF

15. Optimization and qualification of an 8-color intracellular cytokine staining assay for quantifying T cell responses in rhesus macaques for pre-clinical vaccine studies

Author

Donaldson, Mitzi M., primary, Kao, Shing-Fen, additional, Eslamizar, Leila, additional, Gee, Connie, additional, Koopman, Gerrit, additional, Lifton, Michelle, additional, Schmitz, Joern E., additional, Sylwester, Andrew W., additional, Wilson, Aaron, additional, Hawkins, Natalie, additional, Self, Steve G., additional, Roederer, Mario, additional, and Foulds, Kathryn E., additional

Published
2012
Full Text
View/download PDF

16. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Author

Annie W. Lau-Kilby, Cheng Cheng, Nancy J. Sullivan, Joshua C. Johnson, Clement Asiedu, John C. Trefry, Lingshu Wang, Antonella Folgori, Alfredo Nicosia, Adele Abbate, Kathryn E. Foulds, Richard A. Koup, Fabiana Grazioli, Riccardo Cortese, Gary J. Nabel, Mario Roederer, Daphne A. Stanley, Anna N. Honko, Stefano Colloca, Mitzi M. Donaldson, Lisa E. Hensley, John R. Mascola, Virginia Ammendola, Stanley, Daphne A, Honko, Anna N., Asiedu, Clement, Trefry, John C., Lau Kilby, Annie W., Johnson, Joshua C., Hensley, Lisa, Ammendola, Virginia, Abbate, Adele, Grazioli, Fabiana, Foulds, Kathryn E., Cheng, Cheng, Wang, Lingshu, Donaldson, Mitzi M., Colloca, Stefano, Folgori, Antonella, Roederer, Mario, Nabel, Gary J., Mascola, John, Nicosia, Alfredo, Cortese, Riccardo, Koup, Richard A., and Sullivan, Nancy J.

Subjects
Protective immunity, Time Factors, Pan troglodytes, Time Factor, Genetic Vectors, Immunization, Secondary, Chimpanzee adenovirus, Vaccinia virus, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Ebolaviru, Adenovirus Vaccines, medicine, Animals, Humans, Defective Viruse, Ebola Vaccine, Ebola Vaccines, Macaca fasciculari, Ebolavirus, Biochemistry, Genetics and Molecular Biology (all), Ebola vaccine, Animal, Adenoviruses, Human, Medicine (all), Pan troglodyte, Defective Viruses, General Medicine, Hemorrhagic Fever, Ebola, Virology, Vaccinia viru, Vaccination, Macaca fascicularis, Adenovirus Vaccine, Immunology, Adenoviruses, Simian, RNA, Viral, Female, Genetic Vector, Human
Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

Published
2014

17. Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates.

Author

Corbett KS, Gagne M, Wagner DA, Connell SO, Narpala SR, Flebbe DR, Andrew SF, Davis RL, Flynn B, Johnston TS, Stringham C, Lai L, Valentin D, Van Ry A, Flinchbaugh Z, Werner AP, Moliva JI, Sriparna M, O'Dell S, Schmidt SD, Tucker C, Choi A, Koch M, Bock KW, Minai M, Nagata BM, Alvarado GS, Henry AR, Laboune F, Schramm CA, Zhang Y, Wang L, Choe M, Boyoglu-Barnum S, Shi W, Lamb E, Nurmukhambetova ST, Provost SJ, Donaldson MM, Marquez J, Todd JM, Cook A, Dodson A, Pekosz A, Boritz E, Ploquin A, Doria-Rose N, Pessaint L, Andersen H, Foulds KE, Misasi J, Wu K, Carfi A, Nason MC, Mascola J, Moore IN, Edwards DK, Lewis MG, Suthar MS, Roederer M, McDermott A, Douek DC, Sullivan NJ, Graham BS, and Seder RA

Abstract

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.1.351 (beta or β) variant. Reciprocal ID 50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the β variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost β-specific reciprocal ID 50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the β variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations., One-Sentence Summary: mRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.

Published
2021
Full Text
View/download PDF

18. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates.

Author

Corbett KS, Nason MC, Flach B, Gagne M, O' Connell S, Johnston TS, Shah SN, Edara VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona OM, Werner AP, Alvarado GS, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, Faudree A, Greenhouse J, Kar S, Pessaint L, Porto M, Steingrebe K, Valentin D, Zouantcha S, Bock KW, Minai M, Nagata BM, Moliva JI, van de Wetering R, Boyoglu-Barnum S, Leung K, Shi W, Yang ES, Zhang Y, Todd JM, Wang L, Andersen H, Foulds KE, Edwards DK, Mascola JR, Moore IN, Lewis MG, Carfi A, Montefiori D, Suthar MS, McDermott A, Sullivan NJ, Roederer M, Douek DC, Graham BS, and Seder RA

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP., One-Sentence Summary: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Published
2021
Full Text
View/download PDF

19. Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates.

Author

Francica JR, Flynn BJ, Foulds KE, Noe AT, Werner AP, Moore IN, Gagne M, Johnston TS, Tucker C, Davis RL, Flach B, O'Connell S, Andrew SF, Lamb E, Flebbe DR, Nurmukhambetova ST, Donaldson MM, Todd JM, Zhu AL, Atyeo C, Fischinger S, Gorman MJ, Shin S, Edara VV, Floyd K, Lai L, Tylor A, McCarthy E, Lecouturier V, Ruiz S, Berry C, Tibbitts T, Andersen H, Cook A, Dodson A, Pessaint L, Ry AV, Koutsoukos M, Gutzeit C, Teng IT, Zhou T, Li D, Haynes BF, Kwong PD, McDermott A, Lewis MG, Fu TM, Chicz R, van der Most R, Corbett KS, Suthar MS, Alter G, Roederer M, Sullivan NJ, Douek DC, Graham BS, Casimiro D, and Seder RA

Abstract

Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody F C receptors mediating effector functions in vitro . Pseudovirus and live virus neutralizing IC 50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×10 6 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials., Competing Interests: Declaration of interests All authors have declared the following interests: VL, TB, CB, SR, TMF, DC, RC are Sanofi Pasteur employees and may hold stock. MK, RvdM, and CG are employees of the GSK group of companies and report ownership of GSK shares.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results