Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques

• Published in: Infection and immunity 2001-09, Vol.69 (9), p.5565-5572
• Main Authors: ROGERS, William O, BAIRD, J. Kevin, HOFFMAN, Stephen L, KUMAR, Anita, TINE, John A, WEISS, Walter, AGUIAR, Joao C, GOWDA, Kalpana, GWADZ, Robert, KUMAR, Sanjai, GOLD, Mark
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - blood; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Protozoan - metabolism; apical merozoite antigen 1; Avipoxvirus - genetics; Avipoxvirus - immunology; Bacteriology; Biological and medical sciences; circumsporozoite protein; Fundamental and applied biological sciences. Psychology; Fungal and Parasitic Infections; Human protozoal diseases; Immunization, Secondary - methods; Infectious diseases; Interferon-gamma - biosynthesis; Macaca mulatta; Malaria; Malaria - prevention & control; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Medical sciences; merozoite surface protein 1; Mice; Microbiology; Parasitemia - prevention & control; Parasitic diseases; PkAMA1 protein; PkCSP protein; PkMSP1 protein; PkSSP2 protein; Plasmids - genetics; Plasmodium knowlesi; Plasmodium knowlesi - immunology; Protozoal diseases; sporozoite surface protein 2; Tumor Cells, Cultured; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.69.9.5565-5572.2001

A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria species Plasmodium knowlesi including two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen 1 (PkAMA1) and merozoite surface protein 1 (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100 P. knowlesi sporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development.