TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

Abstract

The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 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 SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/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 SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine.

Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model

“…The safety of K3-SPG in primate was proven in current study and also in other study with cynomolgus monkey ( Macaca fascicularis ) for influenza vaccine 15. Besides, the safety of K3 adjuvant has already confirmed in cynomolgus and squirrel monkeys in the study of malaria vaccine,26 and SPG has been used as a cancer therapy in Japan for many years, and no severe side effects have been associated with its use to date 27…”

Evaluation of the immune response and protective efficacy of Schistosoma mansoni Cathepsin B in mice using CpG dinucleotides as adjuvant

“…Moreover, we have chosen synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides as the adjuvant. The use of CpG dinucleotides as adjuvants has shown promise in experimental vaccines against other parasitic infections such as malaria and leishmaniasis [24][25][26][27][28]. Furthermore, these Toll-like receptor 9 agonists are known to stimulate Th1 responses.…”

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

“…The monkeys were immunized subcutaneously twice within a 3-week interval and at 9-weeks after the first immunization received a challenge infection of 5 × 10 8 parasites. Monkeys immunized with BK-SE36 and K3 CpG effectively suppressed parasitemia 38) . Anti-SE36 antibody titer was also subsequently boosted by malaria infection.…”

“…A study to optimize the immunogenicity of BK-SE36 was done in combination with K3 CpG (ATCGACTCTCGAGCGTTCTC), D35 CpG (GG tgcatcgatgcaggggGG) (GeneDesign, Inc), or synthetic hemozoin (sHZ) as adjuvant 38) . .…”