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Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria.

E G Rodrigues, F Zavala, D Eichinger, J M Wilson and M Tsuji
J Immunol February 1, 1997, 158 (3) 1268-1274;
E G Rodrigues
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F Zavala
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D Eichinger
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J M Wilson
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M Tsuji
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Abstract

The immunogenicity of a recombinant replication defective adenovirus expressing a major malaria Ag, the circumsporozoite (CS) protein (AdPyCS), was determined using a rodent malaria model. A single immunizing dose of this construct induced a large number of CS-specific CD8+ and CD4+ T cells in the spleens of these animals, particularly when given by the s.c. or i.m. route. A single dose of AdPyCS also induced high titers of Abs to Plasmodium yoelii sporozoites in mice. No other form of presentation of the CS protein given as a single immunizing dose, i.e., irradiated sporozoites, recombinant vaccinia, or influenza virus, etc., elicits comparably high numbers of CS-specific CD8+ T cells. The high concentration of CS-specific CD8+ T cells in the spleen was relatively short-lived, decreasing to half of its original value by 4 wk and to one-third at 8 wk after AdPyCS inoculation. The decrease in splenic CS-specific CD4+ T cells was even more rapid. Most importantly, a single dose of inoculation of AdPyCS into mice rendered them highly resistant to sporozoite challenge, resulting in a 93% inhibition of liver stage development of the parasites. This protective effect was primarily mediated by CD8+ T cells, as shown by depletion of this T cell population, while depletion of the CD4+ T cell population had only a minor effect on anti-plasmodial activity. Moreover, the inoculation of mice with AdPyCS induces sterile immunity in a significant proportion of mice, preventing the occurrence of parasitemia.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 3
1 Feb 1997
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Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria.
E G Rodrigues, F Zavala, D Eichinger, J M Wilson, M Tsuji
The Journal of Immunology February 1, 1997, 158 (3) 1268-1274;

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Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria.
E G Rodrigues, F Zavala, D Eichinger, J M Wilson, M Tsuji
The Journal of Immunology February 1, 1997, 158 (3) 1268-1274;
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Print ISSN 0022-1767        Online ISSN 1550-6606