The Challenges and Opportunities of Next-Generation Rotavirus Vaccines: Summary of an Expert Meeting with Vaccine Developers

Abstract

The 2nd Next Generation Rotavirus Vaccine Developers Meeting, sponsored by PATH and the Bill and Melinda Gates Foundation, was held in London, UK (7–8 June 2022), and attended by vaccine developers and researchers to discuss advancements in the development of next-generation rotavirus vaccines and to consider issues surrounding vaccine acceptability, introduction, and uptake. Presentations included updates on rotavirus disease burden, the impact of currently licensed oral vaccines, various platforms and approaches for next generation rotavirus vaccines, strategies for combination pediatric vaccines, and the value proposition for novel parenteral rotavirus vaccines. This report summarizes the information shared at the convening and poses various topics worthy of further exploration.

WITHDRAWN: Molecular Analysis of Non-structural Protein 1 (NSP1) in Children Infected with Rotavirus in Babylon Province, Iraq: A Cross-Sectional Study

“…Since 1973, rotavirus has been found responsible for causing life-threatening, acute dehydrating gastroenteritis across the world, not only in infants and young children (Bishop et al 1973; Flewett et al 1973) who are particularly susceptible to infection, but also in older individuals in whom the infection is typically mild or even asymptomatic owing to the exposure-induced immunity developed over time in response to repeated infections (Parashar et al 1998). Following all aforementioned discoveries, nowadays rotaviruses are recognized as the most predominant diarrheal pathogens (Parashar et al 1998), and rotavirus-associated diarrhea, also referred to as rotaviral diarrhea, is identified as the primary cause of viral diarrhea in the world (Chen et al 2022).…”

“…Following all aforementioned discoveries, nowadays rotaviruses are recognized as the most predominant diarrheal pathogens (Parashar et al 1998), and rotavirus-associated diarrhea, also referred to as rotaviral diarrhea, is identified as the primary cause of viral diarrhea in the world (Chen et al 2022).…”

Novel mRNA-based VP8* vaccines against rotavirus are highly immunogenic in rodents

“…There are currently no correlates of protection established for live-attenuated oral rotavirus vaccines, let alone for non-replicating parenteral vaccines. It seems likely that these vaccine types have different protective mechanisms and thus feature distinct correlates of protection 59 . Therefore, it is unclear how the promising preclinical results of mRNA-based rotavirus vaccines will translate to humans.…”

“…Therefore, it is unclear how the promising preclinical results of mRNA-based rotavirus vaccines will translate to humans. Unfortunately, the ongoing phase 3 clinical trial (NCT04010448) assessing safety and efficacy of the trivalent P2-VP8* protein vaccine met futility criteria at interim analysis as the protein vaccine demonstrated no superior efficacy to a licensed oral rotavirus vaccine 59 . However, given the fundamental differences in immune responses elicited by protein and mRNA vaccines 60–62 , it seems conceivable that an mRNA vaccine could perform differently in humans despite the shared antigen.…”

Combined Live Oral Priming and Intramuscular Boosting Regimen with Rotarix® and a Nanoparticle-Based Trivalent Rotavirus Vaccine Evaluated in Gnotobiotic Pig Models of G4P[6] and G1P[8] Human Rotavirus Infection

“…On the contrary, parenteral HRV vaccines have been shown to be highly immunogenic and are now the focus of current efforts to address live oral vaccines’ shortcomings [ 23 ]. Unfortunately, a phase III human trial for a parenteral HRV vaccine was recently terminated due to a lack of improved protective efficacy as compared to currently used live oral attenuated vaccines [ 24 ]. Despite this, parenteral vaccines still may have an important role in protecting against disease.…”