npj Vaccines (Mar 2024)

Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform

  • Marcal Yll-Pico,
  • Yoonsuh Park,
  • Joy Martinez,
  • Angelina Iniguez,
  • Mindy Kha,
  • Taehyun Kim,
  • Leonard Medrano,
  • Vu H. Nguyen,
  • Teodora Kaltcheva,
  • Shannon Dempsey,
  • Flavia Chiuppesi,
  • Felix Wussow,
  • Don J. Diamond

DOI
https://doi.org/10.1038/s41541-024-00859-3
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 11

Abstract

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Abstract Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.