A bacterially expressed triple-type chimeric vaccine against human papillomavirus types 51, 69, and 26

Vaccine. 2022 Oct 6;40(42):6141-6152. doi: 10.1016/j.vaccine.2022.09.010. Epub 2022 Sep 16.

Abstract

Persistent infection of high-risk human papillomavirus (HPV) is a leading cause of some cancers, including cervical cancer. However, with over 20 carcinogenic HPV types, it is difficult to design a multivalent vaccine that can offer complete protection. Here, we describe the design and optimization of a HPV51/69/26 triple-type chimeric virus-like particle (VLP) for vaccine development. Using E. coli and a serial N-terminal truncation strategy, we created double- and triple-type chimeric VLPs through loop-swapping at equivalent surface loops. The lead candidate, H69-51BC-26FG, conferred similar particulate properties as that of its parental VLPs and comparable immunogenicity against HPV51, -69 and -26. When produced in a GMP-like facility, these H69-51BC-26FG VLPs were verified to have excellent qualities for the development of a multivalent HPV vaccine. This study showcases an amenable way to create a single VLP using type-specific epitope clustering for the design of a triple-type vaccine.

Keywords: Human papillomavirus; Neutralizing antibody; Triple-type vaccine; Virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus*
  • Animals
  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • Escherichia coli / genetics
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Papillomaviridae / genetics
  • Papillomavirus Infections*
  • Papillomavirus Vaccines* / genetics
  • Vaccines, Combined
  • Vaccines, Virus-Like Particle* / genetics

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • Papillomavirus Vaccines
  • Vaccines, Combined
  • Vaccines, Virus-Like Particle