Zika virus-like particle (VLP) based vaccine

• Published in: PLoS neglected tropical diseases Vol. 11; no. 5; p. e0005608
• Main Authors: Boigard, Hélène, Alimova, Alexandra, Martin, George R, Katz, Al, Gottlieb, Paul, Galarza, Jose M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2017; Public Library of Science (PLoS)
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Aquatic insects; Biology and life sciences; Birth defects; Cell culture; Cells; Colleges & universities; Congenital defects; Deactivation; Defects; Dengue fever; Disease control; Disease transmission; Disorders; E protein; Electron microscopy; Encephalitis; Epitopes; Female; Formulations; Gene expression; Genetic aspects; Genomes; Guillain-Barre syndrome; Immunoglobulins; Inactivation; Infections; Mammalian cells; Mammals; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Mosquitoes; Motor task performance; Neurological diseases; Neutralization; Neutralizing; Particulates; Parturition; Proteins; Research and Analysis Methods; Serum; Sexual transmission; Suspension; Suspension culture; Testing; Transmission; Tropical diseases; Vaccine development; Vaccines; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Vaccines, Virus-Like Particle - ultrastructure; Vector-borne diseases; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus-like particles; Viruses; Zika virus; Zika Virus - immunology; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control; New York; United States > US
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005608

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development.