A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains

• Published in: Nature (London) Vol. 333; no. 6168; pp. 74 - 76
• Main Authors: Kaslow, David C, Quakyi, Isabella A, Syin, Chiang, Raum, Michael G, Keister, David B, Coligan, John E, McCutchan, Thomas F, Miller, Louis H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 05-05-1988; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Aquatic insects; Base Sequence; Biological and medical sciences; Disease transmission; Epidermal Growth Factor - genetics; Human protozoal diseases; Humans; Infectious diseases; Life cycles; Malaria; Malaria - prevention & control; Malaria - transmission; Medical research; Medical sciences; Molecular Sequence Data; Mosquitoes; Parasites; Parasitic diseases; Plasmodium falciparum - genetics; Plasmodium falciparum - physiology; Protozoal diseases; Tropical medicine; Vaccines; Vaccines - genetics; Vaccines - immunology; Vector-borne diseases; Protozoa; Protozoal disease; Ookinete; Malaria; Nucleotide sequence; Transmission; Blocking; Homology; Vaccine; Research; Sexual reproduction; Cell surface; Infection; Proteins; Plasmodium falciparum; Epidermal growth factor; Gene; Zygote; Developmental stage; Molecular cloning; Sporozoa; Aminoacid sequence
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/333074a0

Malaria vaccines are being developed against different stages in the parasite's life cycle, each increasing the opportunity to control malaria in its diverse settings. Sporozoite vaccines are designed to prevent mosquito-induced infection; first generation recombinant or synthetic peptide vaccines have been tested in humans. Asexual erythrocytic stage vaccines, developed to prevent or reduce the severity of disease, have been tested in animals and in humans. A third strategy is to produce sexual stage vaccines that would induce antibodies which would prevent infection of mosquitoes when ingested in a bloodmeal containing sexual stage parasites. Although not directly protective, the sexual stage vaccine combined with a sporozoite or asexual stage vaccine (protective component) could prolong the useful life of the protective component by reducing transmission of resistant vaccine-induced mutants. In areas of low endemnicity, the sexual stage vaccine could reduce transmission below the critical threshold required to maintain the infected population, thereby assisting in the control or eradication of malaria. Transmission of Plasmodium falciparum, the major human malaria, can be blocked by monoclonal antibodies against three sexual stage-specific antigens. We have cloned the gene encoding the surface protein of relative molecular mass Mr 25,000 (25K; Pfs25), expressed on zygotes and ookinetes of P. falciparum. The deduced amino-acid sequence consists of a signal sequence, a hydrophobic C-terminus, and four tandem epidermal growth factor EGF-like domains.