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Infection and Immunity, September 2003, p. 5178-5187, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5178-5187.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Vaccination with Novel Immunostimulatory Adjuvants against Blood-Stage Malaria in Mice

Zhong Su,1 Mi-Fong Tam,1 Dragana Jankovic,2 and Mary M. Stevenson1*

Centre for the Study of Host Resistance, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec, Canada,1 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland2

Received 29 January 2003/ Returned for modification 8 April 2003/ Accepted 27 May 2003

An important aspect of malaria vaccine development is the identification of an appropriate adjuvant which is both capable of stimulating a protective immune response and safe for use by humans. Here, we investigated the feasibility of using novel immunostimulatory molecules as adjuvants combined with a crude antigen preparation and coadsorbed to aluminum hydroxide (alum) as a vaccine against blood-stage Plasmodium chabaudi AS malaria. Prior to challenge infection, immunization of genetically susceptible A/J mice with the combination of malaria antigen plus recombinant interleukin-12 (IL-12) in alum induced a Th1 immune response with production of high levels of gamma interferon (IFN-{gamma}) and diminished IL-4 levels by spleen cells stimulated in vitro with parasite antigen compared to mice immunized with antigen alone, antigen in alum, or antigen plus IL-12. Mice immunized with malaria antigen plus recombinant IL-12 in alum had high levels of total malaria-specific antibody and immunoglobulin G2a. Compared to unimmunized mice, immunization with antigen plus IL-12 in alum induced the highest level of protective immunity against challenge infection with P. chabaudi AS, which was evident as a significantly decreased peak parasitemia level and 100% survival. Protective immunity was dependent on CD4+ T cells, IFN-{gamma}, and B cells and was long-lasting. Replacement of IL-12 as an adjuvant by synthetic oligodeoxynucleotides (ODN) containing CpG motifs induced a similar level of vaccine-induced protection against challenge infection with P. chabaudi AS. These results illustrate that it is possible to enhance the potency of a crude malaria antigen preparation delivered in alum by inclusion of immunostimulatory molecules, such as IL-12 or CpG-ODN.

* Corresponding author. Mailing address: Montreal General Hospital Research Institute, MUHC RI, Room L11-409, 1650 Cedar Ave., Montreal, Quebec H3G 1A4, Canada. Phone: (514) 934-1934, ext. 44507. Fax: (514) 934-8332. E-mail: mary.m.stevenson{at}mcgill.ca.

Editor: J. M. Mansfield

Infection and Immunity, September 2003, p. 5178-5187, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5178-5187.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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