AAV vectors encoding malarial antigens stimulate antigen-specific immunity but do not protect from parasite infection.
This study explores the utility of recombinant adeno-associated virus (rAAV) as a genetic vaccine delivery system using muscle as a target tissue. A single injection of rAAV encoding the malarial antigens MSP4 (Plasmodium falciparum) or MSP4/5 (Plasmodium yoelii) stimulated long-term antigen-specific antibody responses. Anti-MSP4/5 immunity stimulated by AAV was not protective against P. yoelii infection and efforts taken to augment antibody responses against MSP4/5, either by priming with plasmid DNA or AAV and boosting with rAAV were unsuccessful. Alternative strategies such as inclusion of genetic adjuvants into the AAV vector will be necessary to stimulate an adequate level of anti-malarial protective immunity in this model.
Logan
Grant J
GJ
Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Westmead, Australia.
Wang
Lina
L
Zheng
Maolin
M
Cunningham
Sharon C
SC
Coppel
Ross L
RL
Alexander
Ian E
IE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D000939:Epitopes; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007273:Injections, Intramuscular; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology* / Q000469:parasitology; D010967:Plasmodium yoelii / Q000276:immunology* / Q000469:parasitology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C118839:merozoite surface protein 4, Plasmodium; C114957:merozoite surface protein 5