Persistence of protective immunity to malaria induced by DNA priming and poxvirus boosting: characterization of effector and memory CD8⁺-T-cell populations

Sedegah, Martha, Brice, Gary T., Rogers, William O., Doolan, Denise L., Charoenvit, Yupin, Jones, Trevor R., Majam, Victoria F., Belmonte, Arnel, Lu, Minh, Belmonte, Maria, Carucci, Daniel J., and Hoffman, Stephen L. (2002) Persistence of protective immunity to malaria induced by DNA priming and poxvirus boosting: characterization of effector and memory CD8⁺-T-cell populations. Infection and Immunity, 70 (7). pp. 3493-3499.

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Abstract

The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with either high-dose (100 μg of p PyCSP plus 30 μg of pGM-CSF) or low-dose (1 μg of p PyCSP plus 1 μg of pGM-CSF DNA) priming were protected against challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30 to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector CD8⁺-T-cell population present 2 weeks after boosting had ex vivo Ag-specific cytolytic activity, expressed both gamma interferon (IFN-γ) and tumor necrosis factor alpha, and constituted 12 to 20% of splenic CD8⁺ T cells. In contrast, the memory CD8⁺-Ag-specific-cell population at 28 weeks lacked cytolytic activity and constituted only 6% of splenic CD8⁺ T cells, but at the single-cell level it produced significantly higher levels of IFN-γ than the effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was similarly immunogenic and as protective as high-dose priming against a 50-, but not a 250-, sporozoite challenge. These results demonstrate that a heterologous priming and boosting vaccination can provide lasting protection against malaria in this model system.

Item ID: 42761
Item Type: Article (Refereed Research - C1)
ISSN: 1098-5522
Funders: Naval Medical Research Centre (NMRC), Office of Naval Research (ONR)
Projects and Grants: NMRC 61102A.S13.F.A0009, NMRC 62787A.870.F.A0010, NMRC Military Infectious Diseases Research Program, ONR grant N00014-89-J-1856
Date Deposited: 22 Mar 2016 23:52
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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