Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36.

Abstract

An effective malaria vaccine is a public health priority. Proteins expressed during the blood-stage of the parasite life cycle have been proposed as good vaccine candidates. No such blood-stage vaccine, however, is available against Plasmodium falciparum, the deadliest Plasmodium species. We show here that P. falciparum serine repeat antigen 5 (SERA5) is a potential vaccine immunogen. We have constructed a new recombinant molecule of SERA5, namely SE36, based on previously reported SE47' molecule by removing the serine repeats. Epidemiological study in the holo-endemic population of Solomon Islands shows highly significant correlation of sero-conversion and malaria protective immunity against this antigen. Animal experiments using non-human primates, and a human phase 1a clinical trial assessed SE36 vaccine immunogenicity. Vaccination of squirrel monkeys with SE36 protein and aluminum hydroxyl gel (SE36/AHG) conferred protection against high parasitemia and boosted serum anti-SE36 IgG after P. falciparum parasite challenge. SE36/AHG was highly immunogenic in chimpanzees, where serum anti-SE36 IgG titers last more than one year. Phase 1a clinical trial (current controlled trials, ISRCTN78679862) demonstrated the safety and immunogenicity of SE36/AHG with 30 healthy adults and 10 placebo controls. Three subcutaneous administrations of 50 and 100microg dose of SE36/AHG were well-tolerated, with no severe adverse events; and resulted in 100% sero-conversion in both dose arms. The current research results for SE36/AHG provide initial clinical validation for future trials and suggest clues/strategies for further vaccine development.

• Authors: Toshihiro Horii, Hiroki Shirai, Li Jie, Ken J Ishii, Nirianne Q Palacpac, Takahiro Tougan, Mariko Hato, Nobuo Ohta, Albino Bobogare, Nana Arakaki, Yoshitsugu Matsumoto, Junko Namazue, Toyokazu Ishikawa, Shigeharu Ueda, Michiaki Takahashi
• Journal: Parasitology international (Parasitol Int) Vol. 59 Issue 3 Pg. 380-6 (Sep 2010) ISSN: 1873-0329 [Electronic] Netherlands
• PMID: 20493274 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Immunoglobulin G
• Malaria Vaccines
• Recombinant Proteins
• serine repeat antigen 5, Plasmodium falciparum

Topics

• Adult
• Animals
• Antigens, Protozoan (genetics, immunology)
• Drug Evaluation, Preclinical
• Humans
• Immunoglobulin G (blood)
• Malaria Vaccines (administration & dosage, genetics, immunology)
• Malaria, Falciparum (epidemiology, parasitology, prevention & control)
• Melanesia (epidemiology)
• Parasitemia (epidemiology, parasitology, prevention & control)
• Plasmodium falciparum (immunology)
• Recombinant Proteins (genetics, immunology)
• Saimiri
• Treatment Outcome
• Vaccination