Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP

Sci Rep. 2018 Feb 21;8(1):3390. doi: 10.1038/s41598-018-21630-4.

Abstract

Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8+ T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A_A_M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Simian / immunology
  • Adolescent
  • Adult
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes / immunology*
  • Female
  • Genetic Vectors / immunology*
  • Humans
  • Immunization, Secondary / methods
  • Liver / immunology*
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology*
  • Male
  • Middle Aged
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / immunology
  • Vaccination / methods
  • Vaccinia / immunology
  • Vaccinia virus / immunology
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes
  • Malaria Vaccines
  • Protozoan Proteins