Genetic immunisation by liver stage antigen 3 protects chimpanzees against malaria despite low immune responses

• Published in: PloS one Vol. 3; no. 7; p. e2659
• Main Authors: Daubersies, Pierre, Ollomo, Benjamin, Sauzet, Jean-Pierre, Brahimi, Karima, Perlaza, Blanca-Liliana, Eling, Wijnand, Moukana, Hubert, Rouquet, Pierre, de Taisne, Charles, Druilhe, Pierre
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.07.2008; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Antigens, Protozoan - metabolism; Apes; Chimpanzees; Culicidae; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA vaccines; Epitopes - chemistry; Erythrocytes; Ethics; Immune response; Immune System; Immunity, Innate; Immunization; Immunogenicity; Infectious Diseases; Liver; Malaria; Malaria - genetics; Malaria - metabolism; Malaria - prevention & control; Malaria Vaccines - chemistry; Models, Genetic; Pan troglodytes; Parasites; Plasmodium falciparum; Plasmodium falciparum - metabolism; Plasmodium yoelii - metabolism; Protection and preservation; Schistosoma; Treatment Outcome; Vaccines; Vaccines, DNA; Vector-borne diseases; Virulence (Microbiology)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0002659

The true interest of genetic immunisation might have been hastily underestimated based on overall immunogenicity data in humans and lack of parallelism with other, more classical immunisation methods. Using malaria Liver Stage Antigen-3 (LSA-3), we report that genetic immunization induces in chimpanzees, the closest relative of humans, immune responses which are as scarce as those reported using other DNA vaccines in humans, but which nonetheless confer strong, sterile and reproducible protection. The pattern was consistent in 3/4 immunized apes against two high dose sporozoite challenges performed as late as 98 and 238 days post-immunization and by a heterologous strain. These results should, in our opinion, lead to a revisiting of the value of this unusual means of immunisation, using as a model a disease, malaria, in which virulent challenges of volunteers are ethically acceptable.