Immune response to rotavirus vaccines in low- and middle-income countries: Challenges and perspectives

Rotavirus is a highly contagious pathogen and a leading cause of severe diarrhea cases in children under 5 y of age worldwide. Although effective oral rotavirus vaccines have been developed and implemented globally, their performance varies substantially by setting. In high-income countries (HICs), these oral vaccines exhibit 85-90% efficacy in preventing rotavirus-associated hospitalizations, with protection lasting until at least 2 y of age. In contrast, vaccine efficacy in low- and middle-income countries (LMICs) is considerably lower, ranging from approximately 45% to 65%. To address this disparity, efforts are underway to develop next-generation rotavirus vaccines. In this review, we critically examine the immune responses elicited by natural rotavirus infection and by oral vaccination in both HICs and LMICs. The goal is to identify immunological factors associated with durable protection and to define key characteristics that an improved rotavirus vaccine should possess to achieve sustained high efficacy in LMICs.