Vaccine synergy with virus-like particle and immune complex platforms for delivery of human papillomavirus L2 antigen

Vaccine. 2019 Jan 3;37(1):137-144. doi: 10.1016/j.vaccine.2018.11.021. Epub 2018 Nov 17.

Abstract

Diverse HPV subtypes are responsible for considerable disease burden worldwide, necessitating safe, cheap, and effective vaccines. The HPV minor capsid protein L2 is a promising candidate to create broadly protective HPV vaccines, though it is poorly immunogenic by itself. To create highly immunogenic and safe vaccine candidates targeting L2, we employed a plant-based recombinant protein expression system to produce two different vaccine candidates: L2 displayed on the surface of hepatitis B core (HBc) virus-like particles (VLPs) or L2 genetically fused to an immunoglobulin capable of forming recombinant immune complexes (RIC). Both vaccine candidates were potently immunogenic in mice, but were especially so when delivered together, generating very consistent and high antibody titers directed against HPV L2 (>1,000,000) that correlated with virus neutralization. These data indicate a novel immune response synergy upon co-delivery of VLP and RIC platforms, a strategy that can be adapted generally for many different antigens.

Keywords: Human papillomavirus; Minor capsid protein; Recombinant immune complex; Vaccine; Virus-like particle.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigen-Antibody Complex / genetics
  • Antigen-Antibody Complex / immunology*
  • Antigens, Viral / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Female
  • Genetic Vectors
  • Hepatitis B virus / genetics
  • Immunogenicity, Vaccine*
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Nicotiana / genetics
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus Infections / prevention & control
  • Papillomavirus Vaccines / genetics
  • Papillomavirus Vaccines / immunology*
  • Recombinant Proteins / immunology
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigen-Antibody Complex
  • Antigens, Viral
  • Capsid Proteins
  • L2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle