Induction of cell-mediated immunity against mycobacterium tuberculosis using DNA vaccines encoding cytotoxic and helper T-cell epitopes of the 38-kilodalton protein
Dpaj. Fonseca et al., Induction of cell-mediated immunity against mycobacterium tuberculosis using DNA vaccines encoding cytotoxic and helper T-cell epitopes of the 38-kilodalton protein, INFEC IMMUN, 69(8), 2001, pp. 4839-4845
Cell-mediated immune responses are crucial in the protection against tuberc
ulosis. In this study, we constructed DNA vaccines encoding cytotoxic T lym
phocytes (CTL) and T helper cell (Th) epitopes of the 38-kDa lipoglycoprote
in of Mycobacterium tuberculosis and analyzed and compared their immunogeni
cities with that of pXJ38, a DNA vaccine encoding the entire 38-kDa protein
(X. Zhu, N. Venkataprasad, H. S. Thangaraj, M. Hill, M. Singh, J. Ivanyi,
and H. M. Vordermeier, J. Immunol. 158:5921-5926, 1997). Plasmid DNAs encod
ing a CTL epitope, P3 (pP3), a Th epitope (vTh), or both the Th and the P3
epitopes (pThP3) were prepared and tested in C57BL6/J (H-2(b)) mice. Our re
sults confirmed that DNA immunization with pXJ38 induces strong CD8(+) CTL
and Th1 responses (high gamma interferon [IFN-gamma], low interleukin-4 [IL
-4]). Coadministration of plasmid DNAs encoding a Th epitope with those enc
oding a CTL epitope (vTh+pP3) elicited both antigen-specific CD8(+) CTL and
Th1 responses. High levels of IFN-gamma were secreted by spleen cells from
all plasmid DNA-vaccinated mice after in vitro stimulation with the recomb
inant 38-kDa protein. Small or undetectable amounts of IL-4 were observed,
which indicates the induction of a Th1-like response. Multiple-epitope vacc
ination by vTh+pP3 or pThP3 resulted in a broader Th1 response to peptide o
r epitopes than the single-epitope plasmid DNAs. Antigen-specific immunoglo
bulin G2a was only detected in sera from mice immunized with the plasmid pX
J38, and not in mice immunized with the epitope-based DNA vaccines. Thus, t
he absence of an antibody response after immunization with epitope plasmid
DNAs and their ability to trigger only a specific cellular immune response
may prove to be important advantages for a vaccine against tuberculosis.