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

• Published in: Vaccine 2019-01, Vol.37 (1), p.137-144
• Main Authors: Diamos, Andrew G., Larios, Dalia, Brown, Lauren, Kilbourne, Jacquelyn, Kim, Hyun Soon, Saxena, Divyasha, Palmer, Kenneth E., Mason, Hugh S.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigen-Antibody Complex - genetics; Antigen-Antibody Complex - immunology; Antigen-antibody complexes; Antigens; Antigens, Viral - immunology; Capsid protein; Capsid Proteins - genetics; Capsid Proteins - immunology; Drug delivery systems; Female; Genes; Genetic Vectors; Hepatitis B; Hepatitis B virus - genetics; Human papillomavirus; Immune response; Immune system; Immunization; Immunogenicity; Immunogenicity, Vaccine; Immunoglobulins; Immunotherapy; Mice, Inbred BALB C; Minor capsid protein; Neutralization; Neutralization Tests; Nicotiana - genetics; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - genetics; Papillomavirus Vaccines - immunology; Platforms; Proteins; Recombinant immune complex; Recombinant Proteins - immunology; Transgenic plants; Vaccine; Vaccines; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Virus-like particle; Virus-like particles; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.11.021

•HPV-16 L2 N-terminal segment displayed on virus-like particles or in recombinant immune complexes is highly immunogenic.•Delivering both vaccines together synergistically enhanced immunogenicity.•Codelivery produced consistent and high anti-L2 antibody titers (>1,000,000).•The virus-like particles used in this study were produced by a single plant leaf. 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.