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*
Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910;
Department of Microbiology, University of Maryland School of Medicine, Baltimore, MD 21201;
Virogenetics Corp., Troy, NY 12180;
§
Department of Molecular Microbiology and Immunology Johns Hopkins University, Baltimore, MD; and
¶
Vical Inc., San Diego, CA 92121
Intramuscular immunization with a naked DNA plasmid expressing the
Plasmodium yoelii circumsporozoite
protein (pPyCSP) protects mice against challenge with
P. yoelii sporozoites. This protection can be improved
either by coadministration of a plasmid expressing murine GM-CSF
(pGMCSF) or by boosting with recombinant poxvirus expressing the
PyCSP. We now report that combining these two
strategies, by first mixing the priming dose of pPyCSP
with pGMCSF and then boosting with recombinant virus, can substantially
increase vaccine effectiveness. Not only were immune responses and
protection improved but the pPyCSP dose could be lowered
from 100 µg to 1 µg with little loss of immunogenicity after boost
with recombinant poxvirus. Comparing mice primed by the 1-µg doses of
pPyCSP plus 1 µg pGMCSF with mice primed by 1-µg
doses of pPyCSP alone, the former were better protected
(60% vs 0) and had higher concentrations of Abs (titers of 163, 840 vs
5, 120 by indirect fluorescent Ab test against sporozoites), more ex
vivo CTL activity (25% vs 7% specific lysis), and more
IFN-
-secreting cells by enzyme-linked immunospot assay (1460 vs 280
IFN- spot-forming cells/106 cells). Priming with plasmid
vaccine plus pGMCSF and boosting with recombinant poxviruses strongly
improves the immunogenicity and protective efficacy of DNA vaccination
and allows for significant reduction of dose.
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