Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen - PubMed (original) (raw)

Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen

O Bruña-Romero et al. Proc Natl Acad Sci U S A. 2001.

Abstract

We report that complete protection against malaria and total inhibition of liver stage development and parasitemia was obtained in 100% of BALB/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (CS) protein of Plasmodium yoelii (AdPyCS), followed by a booster with an attenuated recombinant vaccinia virus, expressing the same malaria antigen, VacPyCS. We found increased levels of activated CS-specific CD8(+) and CD4(+) T cells, higher anti-sporozoite antibody titers, and greater protection in these mice, when the time between priming and boosting with these two viral vectors was extended from 2 to 8 or more weeks. Most importantly, by using this immunization regimen, the protection of the immunized mice was found to be long-lasting, namely complete resistance to infection of all animals 3 1/2 months after priming. These results indicate that immunization with AdPyCS generates highly effective memory T and B cells that can be recalled long after priming by boosting with VacPyCS.

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Figures

Figure 1

Figure 1

Time course (in weeks) of immune responses and inhibition of liver stages in mice (groups of three) immunized with 108 pfu of reAd (AdPyCS). (a) Number of CS-specific CD8+ and CD4+, IFN-γ-producing T cells and corresponding antibody titers (IFA). (b) Inhibition of liver stage development expressed as number of copies of_Plasmodium_ 18S rRNA. Mice immunized and challenged at the same time points as in a. Data in a and b represent the mean of two identical experiments.

Figure 2

Figure 2

(#) Effects of a booster given at varying time points (weeks after reAd priming) with 107 pfu VacPyCS (+) and controls (−). (a) CS-specific T cell responses and anti-sporozoite antibody titers and (b) inhibition of liver stage development after sporozoite inoculation. Data in a and_b_ were obtained 2 weeks after booster and are each representative of four experiments.

Figure 3

Figure 3

Activation status and apoptosis rates of CD8+ T cell populations obtained from the liver of mice immunized with reAd alone (control) or boosted with VacPyCS, 2 or 8 weeks after priming with AdPyCS. All data obtained 5 days after booster. Flow cytometry of lymphocytes showing (a) the percentage of CS-specific CD8+ T cells, (b) the percentage of CS-specific (Tet+) CD8+ activated (CD62L−) liver lymphocytes, and (c) the percentage of apoptosis of CS-specific (Tet+) cells.

Figure 4

Figure 4

(*) Persistence of immunity and inhibition of liver-stage development, at various time points (2, 6, 10, and 16 weeks) after recombinant vaccinia virus booster, in mice primed with reAd 8 weeks earlier. (a) Persistence of CS-specific CD8+ and CD4+ T cells and antibody titers. (b) Degree of inhibition of liver stage development.

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