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Infection and Immunity, July 2000, p. 3854-3860, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Tuberculosis DNA Vaccine Encoding Ag85A Is
Immunogenic and Protective When Administered by Intramuscular Needle
Injection but Not by Epidermal Gene Gun Bombardment
Audrey
Tanghe,1
Olivier
Denis,1
Bénédicte
Lambrecht,2
Vinciane
Motte,1
Thierry
van
den Berg,2 and
Kris
Huygen1,*
Mycobacterial Immunology, Pasteur Institute
of Brussels,1 and Veterinary and
Agrochemical Research Center,2 B 1180 Brussels,
Belgium
Received 7 December 1999/Returned for modification 27 March
2000/Accepted 31 March 2000
Immunogenicity and protective efficacy of a DNA vaccine encoding
Ag85A from Mycobacterium tuberculosis were compared in
BALB/c and C57BL (B6 and B10) mice immunized by intramuscular (i.m.) needle injection or epidermal gene gun (gg) bombardment. In BALB/c mice, gg immunization could induce elevated antibody and cytotoxic T
lymphocyte responses with plasmid doses 50-fold lower than those required for i.m. immunization. Interleukin-2 (IL-2) and gamma interferon (IFN-
) secretion, however, was much lower in gg-immunized than in i.m.-immunized BALB/c mice. On the other hand, C57BL mice reacted only very weakly to gg immunization, whereas elevated Ag85A-specific antibody, IL-2, and IFN-
responses (significantly higher than in BALB/c mice) were detected following vaccination by the
i.m. route. Antibody isotypes were indicative of Th2 activation following gg injection of BALB/c and of Th1 activation following i.m.
injection of C57BL mice. Finally, C57BL but not BALB/c mice were
protected by i.m. Ag85A DNA immunization against intravenous M. tuberculosis challenge, as measured by reduced
numbers of CFU in spleen and lungs, compared to animals vaccinated with
control DNA. Gene gun immunization was not effective in either BALB/c or C57BL mice. These results indicate that i.m. DNA vaccination is the
method of choice for the induction of protective Th1 type immune
responses with the Ag85A tuberculosis DNA vaccine.
*
Corresponding author. Mailing address: Mycobacterial
Immunology, Pasteur Institute of Brussels, 642 Engelandstraat, B1180 Brussels, Belgium. Phone: 32-2-373-33-70. Fax: 32-2-373-33-67. E-mail:
chuygen{at}ben.vub.ac.be.
Infection and Immunity, July 2000, p. 3854-3860, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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