Incorporation of RG1 epitope into HPV16L1-VLP does not compromise L1-specific immunity

Vaccine. 2019 Jun 12;37(27):3529-3534. doi: 10.1016/j.vaccine.2019.05.011. Epub 2019 May 27.

Abstract

The candidate pan-Human Papillomavirus (HPV) vaccine RG1-VLP are HPV16 major capsid protein L1 virus-like-particles (VLP) comprising a type-common epitope of HPV16 minor capsid protein L2 (RG1; aa17-36). Vaccinations have previously demonstrated efficacy against genital high-risk (hr), low-risk (lr) and cutaneous HPV. To compare RG1-VLP to licensed vaccines, rabbits (n = 3) were immunized thrice with 1 µg, 5 µg, 25 µg, or 125 µg of RG1-VLP or a 1/4 dose of Cervarix®. 5 µg of RG1-VLP or 16L1-VLP (Cervarix) induced comparable HPV16 capsid-reactive and neutralizing antibodies titers (62,500/12,500-62,500 or 1000/10,000). 25 µg RG1-VLP induced robust cross-neutralization titers (50-1000) against hrHPV18/31/33/45/52/58/26/70. To mimic reduced immunization schedules in adolescents, mice (n = 10) were immunized twice with RG1-VLP (5 µg) plus 18L1-VLP (5 µg). HPV16 neutralization (titers of 10,000) similar to Cervarix and Gardasil and cross-protection against hrHPV58 vaginal challenge was observed. RG1-VLP vaccination induces hrHPV16 neutralization comparable to similar doses of licensed vaccines, plus cross-neutralization to heterologous hrHPV even when combined with HPV18L1-VLP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Epitopes / genetics
  • Epitopes / immunology*
  • Immunization Schedule
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / genetics
  • Papillomavirus Vaccines / immunology*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Treatment Outcome
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • L2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Vaccines, Virus-Like Particle
  • L1 protein, Human papillomavirus type 16