Development of Single-Round Infectious Rotaviruses as a Platform for Safer and More Effective Vaccines (Kobayashi Lab, in PLOS Pathogens)

Rotavirus remains a leading cause of acute gastroenteritis in infants worldwide, prompting continued development of safer and more effective vaccines. Single-round infectious rotavirus, which lacks a critical replication gene, not only serves as a potentially safe rotavirus vaccine but can also function as an orally-administrable viral vector vaccine. Previously, we developed such a system by deleting a viral capsid gene; however, the current system has two major drawbacks: low protein expression levels and safety concerns. Here, we aimed to overcome these obstacles by introducing large deletions into the viral surface protein genes. This strategy enabled generation of single-round infectious viruses with markedly higher protein expression and a minimal likelihood of viral reversion. Moreover, we applied the system to a non-pathogenic rotavirus vaccine strain backbone, which increases its safety profile even further. Taken together, these improvements represent significant advances in single-round infectious rotavirus technology, making it a safer and more efficient platform for both rotavirus vaccine development and vector-based immunization of humans.

This article was published in PLOS Pathogens on September 15, 2025.

Title: “Single-round infectious rotaviruses with deletions of VP7 or VP4 genes, based on SA11 and WC3 strain backbones, and their potential use as viral vectors”

Authors: Tomohiro Kotaki, Yuta Kanai, Megumi Onishi, Yusuke Sakai, Daisuke Motooka, Zelin Chen, Yasutaka Enoki, Sayuri Komatsu, Katsuhisa Hirai, Shohei Minami, Takahiro Kawagishi, Hiroshi Ushijima, Takeshi Kobayashi

DOI: doi.org/10.1371/journal.ppat.1013484