Oral rotavirus vaccine shedding as a marker of mucosal immunity

• Published in: Scientific reports Vol. 11; no. 1; p. 21760
• Main Authors: Lee, Benjamin, Kader, Md Abdul, Colgate, E. Ross, Carmolli, Marya, Dickson, Dorothy M., Diehl, Sean A., Alam, Masud, Afreen, Sajia, Mychaleckyj, Josyf C., Nayak, Uma, Petri, William A., Haque, Rashidul, Kirkpatrick, Beth D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/590; 631/326/596/1794; 692/308/3187; 692/699/1503/1501; Administration, Oral; Cohort Studies; Diarrhea; Feces - chemistry; Humanities and Social Sciences; Humans; Immunity, Mucosal; Infant; Infants; Mucosal immunity; multidisciplinary; Pediatrics; Rotavirus; Rotavirus - immunology; Rotavirus Infections - prevention & control; Rotavirus Vaccines - analysis; Rotavirus Vaccines - immunology; Science; Science (multidisciplinary); Vaccine efficacy; Vaccines; Vaccines, Attenuated - analysis; Vaccines, Attenuated - immunology; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-01288-1

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.