Construction and evaluation of a multistage combination vaccine against malaria.
Due to the complex life cycle and high antigenic diversity of the malaria parasite, a multistage vaccine may be necessary for optimal protection against the disease. Our previous studies demonstrated that a blood-stage recombinant protein PfCP-2.9 has significant potential for vaccine development and is currently in human clinical trials. This study constructed two recombinant antigens derived from the Plasmodium falciparum CSP, designated PfCSP-C and PfCSP-RC. They were expressed as secreted proteins at high yield (1-3 g/l) in Pichia pastoris and purified by a two-step purification procedure. There was no evidence of antigen competition in mice and rabbits co-immunized with the pre-erythrocytic antigens and PfCP-2.9. Moreover, the immune sera recognized both the blood-stage parasite and sporozoite, and interacted with the NANP repeats of PfCSP. Rabbits antisera to combination antigens strongly inhibited blood-stage parasite growth in vitro. These results suggest that the recombinant antigens are potential candidates for multistage combination vaccines against malarial parasite.
Zhang
Qingfeng
Q
Department of Etiologic Biology and State Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China.
Xue
Xiangyang
X
Qu
Li
L
Pan
Weiqing
W
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010843:Pichia / Q000235:genetics; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic