Oral rotavirus vaccine shedding as a marker of mucosal immunity

Abstract Group A rotaviruses (RVA) remain a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries. Improved immune correlates of protection (CoP) for existing oral vaccines and novel stra...

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Autores principales:	Benjamin Lee, Md Abdul Kader, E. Ross Colgate, Marya Carmolli, Dorothy M. Dickson, Sean A. Diehl, Masud Alam, Sajia Afreen, Josyf C. Mychaleckyj, Uma Nayak, William A. Petri, Rashidul Haque, Beth D. Kirkpatrick
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/561f110b48ad47f184f16e192023a7b9
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spelling	oai:doaj.org-article:561f110b48ad47f184f16e192023a7b92021-11-08T10:50:33ZOral rotavirus vaccine shedding as a marker of mucosal immunity10.1038/s41598-021-01288-12045-2322https://doaj.org/article/561f110b48ad47f184f16e192023a7b92021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01288-1https://doaj.org/toc/2045-2322Abstract Group A rotaviruses (RVA) remain a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries. Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which RVA immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of RVA diarrhea through 2 years of life (RR 0.616, 95% CI 0.392–0.968). Further development of controlled human infection models for group A rotaviruses, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.Benjamin LeeMd Abdul KaderE. Ross ColgateMarya CarmolliDorothy M. DicksonSean A. DiehlMasud AlamSajia AfreenJosyf C. MychaleckyjUma NayakWilliam A. PetriRashidul HaqueBeth D. KirkpatrickNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Lee Md Abdul Kader E. Ross Colgate Marya Carmolli Dorothy M. Dickson Sean A. Diehl Masud Alam Sajia Afreen Josyf C. Mychaleckyj Uma Nayak William A. Petri Rashidul Haque Beth D. Kirkpatrick Oral rotavirus vaccine shedding as a marker of mucosal immunity
description	Abstract Group A rotaviruses (RVA) remain a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries. Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which RVA immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of RVA diarrhea through 2 years of life (RR 0.616, 95% CI 0.392–0.968). Further development of controlled human infection models for group A rotaviruses, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.
format	article
author	Benjamin Lee Md Abdul Kader E. Ross Colgate Marya Carmolli Dorothy M. Dickson Sean A. Diehl Masud Alam Sajia Afreen Josyf C. Mychaleckyj Uma Nayak William A. Petri Rashidul Haque Beth D. Kirkpatrick
author_facet	Benjamin Lee Md Abdul Kader E. Ross Colgate Marya Carmolli Dorothy M. Dickson Sean A. Diehl Masud Alam Sajia Afreen Josyf C. Mychaleckyj Uma Nayak William A. Petri Rashidul Haque Beth D. Kirkpatrick
author_sort	Benjamin Lee
title	Oral rotavirus vaccine shedding as a marker of mucosal immunity
title_short	Oral rotavirus vaccine shedding as a marker of mucosal immunity
title_full	Oral rotavirus vaccine shedding as a marker of mucosal immunity
title_fullStr	Oral rotavirus vaccine shedding as a marker of mucosal immunity
title_full_unstemmed	Oral rotavirus vaccine shedding as a marker of mucosal immunity
title_sort	oral rotavirus vaccine shedding as a marker of mucosal immunity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/561f110b48ad47f184f16e192023a7b9
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Oral rotavirus vaccine shedding as a marker of mucosal immunity

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