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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-gamma ) 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-gamma 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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