Abstract
Group A rotavirus (RVA) is a major cause of severe gastroenteritis in infants and young children globally, despite the availability of live-attenuated vaccines. Challenges such as limited efficacy in low-income regions, safety concerns for immunocompromised individuals, and cold-chain dependency necessitate alternative vaccine strategies. Subunit vaccines, which use specific viral proteins to elicit immunity, provide a safer and more adaptable approach. This review highlights biotechnological advancements in producing subunit vaccines, focusing on recombinant expression systems like bacterial, yeast, insect, mammalian, and plant-based platforms for scalable and cost-effective production of viral proteins. Key innovations include molecular engineering, adjuvant development, and delivery system improvements to enhance vaccine immunogenicity and efficacy. Subunit vaccines and virus-like particles expressed in various systems have demonstrated promising preclinical and clinical results, with some candidates nearing commercial readiness. Reverse vaccinology, combined with Artificial Intelligence and Machine Learning, is driving the development of innovative multiepitope vaccines and antivirals. Strategies such as passive immunization, single-chain antibodies, immunobiotics, and novel antivirals are also explored as alternative management options. The review also underscores advanced genome editing and reverse genetics approaches to improve vaccine design and antiviral therapies. These biotechnological interventions offer hope for equitable and effective control of rotavirus diarrhea, particularly in resource-limited settings, and represent significant progress toward addressing current vaccine limitations.