Despite major advances in rotavirus prevention, significant challenges remain in protecting children in low- and middle-income countries (LMICs), according to a new report summarising discussions from an international rotavirus immunology convening held in Liverpool, UK.
Rotavirus remains a leading cause of severe diarrhoeal disease in children under 5 years of age worldwide. Although oral rotavirus vaccines have dramatically reduced hospitalisations and deaths, their effectiveness is considerably lower in many LMICs than in high-income countries, leaving substantial gaps in protection.
Current Vaccines Leave Protection Gaps
The convening, co-hosted by the University of Liverpool and the University of the Witwatersrand with support from the Gates Foundation, brought together leading experts in immunology, vaccinology, virology, and global health. Participants explored why current vaccines perform differently across populations and discussed strategies to improve future vaccine design.
While existing oral vaccines have had a profound public health impact, experts noted that persistent disparities in vaccine effectiveness highlight the need for a deeper understanding of the immune mechanisms that drive protection against rotavirus infection.
Looking Beyond Serum IgA
A major focus of the meeting was the need to identify better correlates of protection. Serum immunoglobulin A (IgA) is currently the most widely used marker of vaccine response, but researchers agreed that it does not fully explain why some individuals remain protected while others do not.
Emerging evidence suggests that tissue-resident memory T cells, mucosal immune responses, and non-neutralising antibodies may all contribute to protection against rotavirus. Improved understanding of these mechanisms could help guide the development of more effective vaccines and immunisation strategies.
Maternal and Environmental Factors Matter
Experts also highlighted several factors that may influence vaccine performance in LMICs. These include malnutrition, environmental enteric dysfunction, differences in the gut microbiome, concurrent infections, and host genetic factors.
Maternal antibodies were identified as a particularly important area of investigation. Although these antibodies help protect infants early in life, they may also reduce the replication of oral vaccine viruses and dampen vaccine-induced immune responses.
New Tools Driving Vaccine Research
Advances in research technologies are providing new opportunities to address longstanding questions in rotavirus immunology.
Participants highlighted the growing role of human intestinal organoids, controlled human infection models, and reverse genetics platforms in studying vaccine responses and viral pathogenesis. These tools may help researchers identify more reliable immune markers and better understand population-level differences in vaccine effectiveness.
Five Priorities for Future Development
The meeting concluded with a roadmap outlining five key priorities for future research. These include optimising vaccine schedules, investigating nutritional and gut-health interventions, developing next-generation parenteral vaccines, improving oral vaccine formulations, and standardising experimental models and immune assays.
Experts emphasised that progress will require stronger international collaboration, greater access to advanced research tools in LMICs, and sustained investment in vaccine innovation.
The authors concluded that improving understanding of mucosal immunity will be critical to developing more effective rotavirus vaccines and reducing global inequities in childhood diarrhoeal disease.
Reference
Bronowski C et al. Rotavirus mucosal immunology: insights and research priorities from an international convening in Liverpool, March 2024. npj Vaccines 11, 122 (2026).
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