Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine

Sci Rep. 2017 Apr 19;7:46621. doi: 10.1038/srep46621.

Abstract

The leading malaria vaccine in development is the circumsporozoite protein (CSP)-based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy, thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and therefore developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a vaccine composed of a much higher proportion of CSP than in RTS,S. We demonstrate that in BALB/c mice R21 is immunogenic at very low doses and when administered with the adjuvants Abisco-100 and Matrix-M it elicits sterile protection against transgenic sporozoite challenge. Concurrent induction of potent cellular and humoral immune responses was also achieved by combining R21 with TRAP-based viral vectors and protective efficacy was significantly enhanced. In addition, in contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was induced. These studies identify an anti-sporozoite vaccine component that may improve upon the current leading malaria vaccine RTS,S. R21 is now under evaluation in Phase 1/2a clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology
  • Female
  • Hepatitis B Surface Antigens* / chemistry
  • Hepatitis B Surface Antigens* / immunology
  • Hepatitis B Surface Antigens* / pharmacology
  • Immunogenicity, Vaccine*
  • Malaria Vaccines* / chemistry
  • Malaria Vaccines* / immunology
  • Malaria Vaccines* / pharmacology
  • Malaria, Falciparum* / immunology
  • Malaria, Falciparum* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium falciparum / immunology*
  • Vaccines, Virus-Like Particle* / chemistry
  • Vaccines, Virus-Like Particle* / immunology
  • Vaccines, Virus-Like Particle* / pharmacology

Substances

  • Antibodies, Protozoan
  • Hepatitis B Surface Antigens
  • Malaria Vaccines
  • Vaccines, Virus-Like Particle