Twenty years of research on HPV vaccines based on genetically modified lactic acid bacteria: an overview on the gut-vagina axis

Cell Mol Life Sci. 2021 Feb;78(4):1191-1206. doi: 10.1007/s00018-020-03652-2. Epub 2020 Sep 26.

Abstract

Most cervical cancer (CxCa) are related to persistent infection with high-risk human papillomavirus (HR-HPV) in the cervical mucosa, suggesting that an induction of mucosal cell-mediated immunity against HR-HPV oncoproteins can be a promising strategy to fight HPV-associated CxCa. From this perspective, many pre-clinical and clinical trials have proved the potential of lactic acid bacteria (LAB) genetically modified to deliver recombinant antigens to induce mucosal, humoral and cellular immunity in the host. Altogether, the outcomes of these studies suggest that there are several key factors to consider that may offer guidance on improvement protein yield and improving immune response. Overall, these findings showed that oral LAB-based mucosal HPV vaccines expressing inducible surface-anchored antigens display a higher potential to induce particularly specific systemic and mucosal cytotoxic cellular immune responses. In this review, we describe all LAB-based HPV vaccine investigations by reviewing databases from international studies between 2000 and 2020. Our aim is to promote the therapeutic HPV vaccines knowledge and to complete the gaps in this field to empower scientists worldwide to make proper decisions regarding the best strategies for the development of therapeutic HPV vaccines.

Keywords: Cervical cancer; Human papillomavirus; Lactic acid bacteria; Lactobacillus casei; Lactococcus lactis; Vaccine.

Publication types

  • Review

MeSH terms

  • Female
  • Gastrointestinal Microbiome / genetics*
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunity, Mucosal / genetics
  • Immunity, Mucosal / immunology
  • Lactobacillales / genetics*
  • Lactobacillales / immunology
  • Microorganisms, Genetically-Modified / genetics*
  • Microorganisms, Genetically-Modified / immunology
  • Papillomaviridae / drug effects
  • Papillomaviridae / immunology
  • Papillomaviridae / pathogenicity
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / therapeutic use
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / prevention & control
  • Uterine Cervical Neoplasms / virology
  • Vagina / immunology
  • Vagina / microbiology
  • Vagina / virology

Substances

  • Papillomavirus Vaccines