Evidences of Protection Against Blood-Stage Infection of Plasmodium Falciparum by the Novel Protein Vaccine SE36

Parasitol Int. 2010 Sep;59(3):380-6. doi: 10.1016/j.parint.2010.05.002. Epub 2010 May 20.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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