Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Leveraging Beneficial Off-target Effects Of Live-attenuated Rotavirus Vaccines

Prisca Benedicto-Matambo
ORCID logo ,
Julie Bines
ORCID logo ,
Chikondi Malamba-Banda
,
Isaac Tom Shawa
,
Kayla Barnes
,
Arox Wadson Kamn’gona
ORCID logo ,
Daniel Hungerford
,
Kondwani Charles Jambo
,
Miren Iturriza-Gomara
ORCID logo ,
Nigel A. Cunliffe
,
Katie L Flanagan
ORCID logo ,
Khuzwayo Chidiwa Jere
* ORCID logo
Version 1 : Received: 30 January 2022 / Approved: 1 February 2022 / Online: 1 February 2022 (12:34:07 CET)

A peer-reviewed article of this Preprint also exists.

Benedicto-Matambo, P.; Bines, J.E.; Malamba-Banda, C.; Shawa, I.T.; Barnes, K.; Kamng’ona, A.W.; Hungerford, D.; Jambo, K.C.; Iturriza-Gomara, M.; Cunliffe, N.A.; Flanagan, K.L.; Jere, K.C. Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines. Vaccines 2022, 10, 418. Benedicto-Matambo, P.; Bines, J.E.; Malamba-Banda, C.; Shawa, I.T.; Barnes, K.; Kamng’ona, A.W.; Hungerford, D.; Jambo, K.C.; Iturriza-Gomara, M.; Cunliffe, N.A.; Flanagan, K.L.; Jere, K.C. Leveraging Beneficial Off-Target Effects of Live-Attenuated Rotavirus Vaccines. Vaccines 2022, 10, 418.

Abstract

Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalizations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.

Keywords

Rotavirus; off-target effects; neonatal; live attenuated; RV3-BB; epigenetic modulation

Subject

Medicine and Pharmacology, Pediatrics, Perinatology and Child Health

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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