A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates

PLoS One. 2013 Oct 25;8(10):e78407. doi: 10.1371/journal.pone.0078407. eCollection 2013.

Abstract

A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

Publication types

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

MeSH terms

  • Adenoviridae / immunology*
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Pharmaceutic / pharmacology*
  • Animals
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Genetic Vectors / immunology
  • Glycolipids / immunology*
  • Macaca mulatta / immunology
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / immunology*
  • Male
  • Membrane Proteins / immunology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / immunology
  • Primates / immunology
  • Protozoan Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Glycolipids
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium