Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity

Nat Commun. 2018 Dec 18;9(1):5360. doi: 10.1038/s41467-018-07199-6.

Abstract

Sequence variability in surface-antigenic sites of pathogenic proteins is an important obstacle in vaccine development. Over 200 distinct genomic sequences have been identified for human papillomavirus (HPV), of which more than 18 are associated with cervical cancer. Here, based on the high structural similarity of L1 surface loops within a group of phylogenetically close HPV types, we design a triple-type chimera of HPV33/58/52 using loop swapping. The chimeric VLPs elicit neutralization titers comparable with a mix of the three wild-type VLPs both in mice and non-human primates. This engineered region of the chimeric protein recapitulates the conformational contours of the antigenic surfaces of the parental-type proteins, offering a basis for this high immunity. Our stratagem is equally successful in developing other triplet-type chimeras (HPV16/35/31, HPV56/66/53, HPV39/68/70, HPV18/45/59), paving the way for the development of an improved HPV prophylactic vaccine against all carcinogenic HPV strains. This technique may also be extrapolated to other microbes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Genetic Engineering / methods
  • Immunogenicity, Vaccine
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Neutralization Tests
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology
  • Papillomaviridae / genetics
  • Papillomaviridae / immunology*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / genetics
  • Papillomavirus Vaccines / immunology*
  • Phylogeny
  • Specific Pathogen-Free Organisms
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / prevention & control*
  • Uterine Cervical Neoplasms / virology

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines