Tougan T.,Osaka University |
Aoshi T.,Japan National Institute of Biomedical Innovation |
Aoshi T.,Osaka University |
Coban C.,Osaka University |
And 6 more authors.
Human Vaccines and Immunotherapeutics | Year: 2013
The SE 36 antigen, derived from serine repeat antigen 5 (SE RA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE 36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE 36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE 36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE 36/AHG induced higher humoral and cellular immune response compared with SE 36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE 36-specific IgG antibodies in monkeys vaccinated with a combination of SE 36/AHG and adjuvant, as opposed to vaccination with SE 36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE 36/AHG. All monkeys immunized with the combined SE 36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE 36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine. © 2013 Landes Bioscience.