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Infection and Immunity, August 1999, p. 3719-3726, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Immunostimulatory DNA as an Adjuvant in Vaccination against Leishmania major

Katryn J. Stacey,* and Jenefer M. Blackwell

Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom

Received 11 January 1999/Returned for modification 22 February 1999/Accepted 29 April 1999

Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against leishmaniasis. To test this, susceptible BALB/c mice were vaccinated with soluble leishmanial antigen (SLA) with or without CpG ODN as adjuvant and then challenged with Leishmania major metacyclic promastigotes. CpG ODN alone gave partial protection when injected up to 5 weeks prior to infection, and longer if the ODN was bound to alum. To demonstrate an antigen-specific adjuvant effect, a minimum of 6 weeks between vaccination and infection was required. Subcutaneous administration of SLA alone, SLA plus alum, or SLA plus non-CpG ODN resulted in exacerbated disease compared to unvaccinated mice. Mice receiving SLA plus CpG ODN showed a highly significant (P < 5 × 10-5) reduction in swelling compared to SLA-vaccinated mice and enhanced survival compared to unvaccinated mice. The modulation of the response to SLA by CpG ODN was maintained even when mice were infected 6 months after vaccination. CpG ODN was not an effective adjuvant for antibody production in response to SLA unless given together with alum, when it promoted production of immunoglobulin G2a, a Th1-associated isotype. Our results suggest that with an appropriate antigen, CpG ODN would provide a stable, cost-effective adjuvant for use in vaccination against leishmaniasis.

* Corresponding author. Present address: Centre for Molecular and Cellular Biology and Department of Microbiology, University of Queensland, Brisbane, Queensland 4072, Australia. Phone: 61 7 3365 4561. Fax: 61 7 3365 4388. E-mail: K.Stacey{at}cmcb.uq.edu.au.

Infection and Immunity, August 1999, p. 3719-3726, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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