Published online 10 June 2002 doi:10.1084/jem.20020147
© Rockefeller University Press, 0022-1007/2002/6/1565/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 12, June 17, 2002 1565-1573
Vaccination with Heat-killed Leishmania Antigen or Recombinant Leishmanial Protein and CpG Oligodeoxynucleotides Induces Long-Term Memory CD4+ and CD8+ T Cell Responses and Protection Against Leishmania major Infection
Elizabeth G. Rhee1,
Susana Mendez2,
Javeed A. Shah1,
Chang-you Wu1,
Joanna R. Kirman1,
Tara N. Turon1,
Dylan F. Davey1,
Heather Davis3,
Dennis M. Klinman4,
Rhea N. Coler5,
David L. Sacks2 and
Robert A. Seder1
1 Cellular Immunology Section, Vaccine Research Center
2 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892
3 Coley Pharmaceutical Group, Ottawa, Ontario K1Y 4S1, Canada
4 Laboratory of Retrovirology and Immunology, Center for Biologics Evaluation and Research, Federal Drug Administration, Bethesda, MD 20892
5 Infectious Disease Research Institute, Seattle, WA 98104
Address correspondence to Robert A. Seder, Cellular Immunology Section, Vaccine Research Center, Building 40, Room 3512, 40 Convent Drive, MSC 3025, Bethesda, MD 20892. Phone: 301-594-8483; Fax: 301-480-2565; E-mail: rseder{at}mail.nih.gov
CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive cellular immune responses. In this report, the ability of CpG ODN to confer long-term immunity and protection when used as a vaccine adjuvant with a clinical grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant leishmanial protein was studied. In two different mouse models of L. major infection, vaccination with ALM plus CpG ODN was able to control infection and markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6 (B6) mice, respectively, up to 12 wk after immunization. Moreover, B6 mice immunized with ALM plus CpG ODNs were still protected against infectious challenge even 6 mo after vaccination. In terms of immune correlates of protection, ALM plus CpG ODN-vaccinated mice displayed L. major–specific T helper cell 1 and CD8+ responses. In addition, complete protection was markedly abrogated in mice depleted of CD8+ T cells at the time of vaccination. Similarly, mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long-term protection that was dependent on CD8+ T cells in vivo. Together, these data demonstrate that CpG ODN, when used as a vaccine adjuvant with either a recombinant protein or heat-killed leishmanial antigen, can induce long-term protection against an intracellular infection in a CD8-dependent manner.
Key Words: CD4+ T cells • CD8+ T cells • DNA vaccines • parasitic infection • Th cells
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