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SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

The inclusion of infants in the SARS-CoV-2 vaccine rollout is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function requ...

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Autores principales: Garrido, Carolina, Curtis, Alan D., Dennis, Maria, Pathak, Sachi H., Gao, Hongmei, Montefiori, David, Tomai, Mark, Fox, Christopher B., Kozlowski, Pamela A., Scobey, Trevor, Munt, Jennifer E., Mallory, Michael L., Saha, Pooja T., Hudgens, Michael G., Lindesmith, Lisa C., Baric, Ralph S., Abiona, Olubukola M., Graham, Barney S., Corbett, Kizzmekia S., Edwards, Darin, Carfi, Andrea, Fouda, Genevieve, Van Rompay, Koen K. A., De Paris, Kristina, Permar, Sallie R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774290/
https://www.ncbi.nlm.nih.gov/pubmed/34131024
http://dx.doi.org/10.1126/sciimmunol.abj3684
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author Garrido, Carolina
Curtis, Alan D.
Dennis, Maria
Pathak, Sachi H.
Gao, Hongmei
Montefiori, David
Tomai, Mark
Fox, Christopher B.
Kozlowski, Pamela A.
Scobey, Trevor
Munt, Jennifer E.
Mallory, Michael L.
Saha, Pooja T.
Hudgens, Michael G.
Lindesmith, Lisa C.
Baric, Ralph S.
Abiona, Olubukola M.
Graham, Barney S.
Corbett, Kizzmekia S.
Edwards, Darin
Carfi, Andrea
Fouda, Genevieve
Van Rompay, Koen K. A.
De Paris, Kristina
Permar, Sallie R.
author_facet Garrido, Carolina
Curtis, Alan D.
Dennis, Maria
Pathak, Sachi H.
Gao, Hongmei
Montefiori, David
Tomai, Mark
Fox, Christopher B.
Kozlowski, Pamela A.
Scobey, Trevor
Munt, Jennifer E.
Mallory, Michael L.
Saha, Pooja T.
Hudgens, Michael G.
Lindesmith, Lisa C.
Baric, Ralph S.
Abiona, Olubukola M.
Graham, Barney S.
Corbett, Kizzmekia S.
Edwards, Darin
Carfi, Andrea
Fouda, Genevieve
Van Rompay, Koen K. A.
De Paris, Kristina
Permar, Sallie R.
author_sort Garrido, Carolina
collection PubMed
description The inclusion of infants in the SARS-CoV-2 vaccine rollout is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of eight infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high-magnitude IgG binding to RBD, amino-terminal domain, S1 and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4, and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein–3M-052-SE vaccines were well tolerated and highly immunogenic in infant RMs, providing proof of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.
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spelling pubmed-87742902022-01-20 SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques Garrido, Carolina Curtis, Alan D. Dennis, Maria Pathak, Sachi H. Gao, Hongmei Montefiori, David Tomai, Mark Fox, Christopher B. Kozlowski, Pamela A. Scobey, Trevor Munt, Jennifer E. Mallory, Michael L. Saha, Pooja T. Hudgens, Michael G. Lindesmith, Lisa C. Baric, Ralph S. Abiona, Olubukola M. Graham, Barney S. Corbett, Kizzmekia S. Edwards, Darin Carfi, Andrea Fouda, Genevieve Van Rompay, Koen K. A. De Paris, Kristina Permar, Sallie R. Sci Immunol Article The inclusion of infants in the SARS-CoV-2 vaccine rollout is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of eight infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high-magnitude IgG binding to RBD, amino-terminal domain, S1 and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4, and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein–3M-052-SE vaccines were well tolerated and highly immunogenic in infant RMs, providing proof of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19. 2021-06-15 /pmc/articles/PMC8774290/ /pubmed/34131024 http://dx.doi.org/10.1126/sciimmunol.abj3684 Text en https://creativecommons.org/licenses/by/4.0/exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Article
Garrido, Carolina
Curtis, Alan D.
Dennis, Maria
Pathak, Sachi H.
Gao, Hongmei
Montefiori, David
Tomai, Mark
Fox, Christopher B.
Kozlowski, Pamela A.
Scobey, Trevor
Munt, Jennifer E.
Mallory, Michael L.
Saha, Pooja T.
Hudgens, Michael G.
Lindesmith, Lisa C.
Baric, Ralph S.
Abiona, Olubukola M.
Graham, Barney S.
Corbett, Kizzmekia S.
Edwards, Darin
Carfi, Andrea
Fouda, Genevieve
Van Rompay, Koen K. A.
De Paris, Kristina
Permar, Sallie R.
SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title_full SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title_fullStr SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title_full_unstemmed SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title_short SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
title_sort sars-cov-2 vaccines elicit durable immune responses in infant rhesus macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774290/
https://www.ncbi.nlm.nih.gov/pubmed/34131024
http://dx.doi.org/10.1126/sciimmunol.abj3684
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