VLP Therapeutics, Inc. (VLPT) researchers and their colleagues at Boston University and the National Institutes of Health (NIH) have demonstrated that incorporating a modified base known as 5-methylcytidine (5mC) into replicon-based self-amplifying RNA (saRNA) vaccines for COVID-19 can suppress innate immune responses that cause adverse reactions, while maintaining strong immunogenicity.

This replicon platform technology is expected to contribute to the development of novel RNA vaccines that minimize side effects and efficiently induce adaptive immunity — including T cell and B cell responses — against COVID-19 and other pathogens. The study was conducted with support from the NIH and was published online in the journal Science Translational Medicine on November 12 (Eastern Standard Time).

“In collaboration with researchers from Boston University and the NIH, we demonstrated that 5mC-incorporated replicon RNA can suppress excessive type I interferon (IFN-I) production by plasmacytoid dendritic cells (pDCs), while preserving innate immune activation in antigen-presenting cells such as macrophages,” Wataru Akahata, PhD, founder and CEO of VLPT. “This foundational technology holds promise not only for COVID-19 vaccines, but also for future vaccine development against influenza and emerging pandemic pathogens. We hope it will contribute to the design of next-generation vaccines that are low-dose, highly efficient, and have minimal side effects.”

[Download PDF]

  • Title: Incorporation of 5-methylcytidine alleviates RIG-I mediated innate immune response to self-amplifying RNA vaccine
  • Journal: Science Translational Medicine
  • Authors: Wataru Akahata*, Mai Komori, Amber L. Morey, Andrés A. Quiñones-Molina, James B. Hood, Josiane Fofana, Luis Romero, Elizabeth Peters, Jonathan D. Webber, Tyler Meeks, Paulina A. Przygonska, Isabel Steinberg, Ellison Ober, Tae Kim, Daniel C. Rogan, Kenta Matsuda, Jonathan F. Smith, Suryaram Gummuluru, Mark Connors, and Hisashi Akiyama* (*Corresponding authors)
  • DOI:1126/scitranslmed.adz227
  • URL: https://www.science.org/doi/10.1126/scitranslmed.adz2276
  • Published: November 12, 2025

# # #

About VLP Therapeutics: VLP Therapeutics, Inc. (VLPT), co-founded in 2013 by Drs. Wataru Akahata, Ryuji Ueno, and Sachiko Kuno, is a Maryland, US-based biotech company with a mission to address unmet medical needs worldwide and expand the frontiers of prophylactic and therapeutic immunotherapy. VLPT is currently engaged in research and development of cancer treatment as well as infectious disease prevention.