This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Near, K. A. Articles by Kaslow, D. C. Search for Related Content PubMed PubMed Citation Articles by Near, K. A. Articles by Kaslow, D. C.

 Previous Article  |  Next Article 

Infection and Immunity, February 2002, p. 692-701, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.692-701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Improved Immunogenicity and Efficacy of the Recombinant 19-Kilodalton Merozoite Surface Protein 1 by the Addition of Oligodeoxynucleotide and Aluminum Hydroxide Gel in a Murine Malaria Vaccine Model

Karen A. Near,^* Anthony W. Stowers, Dragana Jankovic, and David C. Kaslow^,

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425

Received 31 August 2001/ Accepted 6 November 2001

Vaccination of mice with yeast-secreted Plasmodium yoelii-derived 19-kilodalton merozoite surface protein 1 (yMSP1₁₉) has been shown to afford protection from challenge with a lethal strain of P. yoelii. Sterile immunity can be achieved when MSP1₁₉ is emulsified in Freund adjuvant but not when it is adsorbed to aluminum hydroxide gel (alum). Because complete Freund adjuvant is not an acceptable adjuvant for use in humans, alternative adjuvants must be identified for formulating MSP1₁₉ as a vaccine for use in humans. To determine whether oligodeoxynucleotides with CpG motifs (ODN), reported to be a powerful new class of adjuvants, could enhance the immunogenicity of yMSP1₁₉, C57BL/6 mice were vaccinated either with yMSP1₁₉ formulated with Freund adjuvant, with alum, or with ODN plus alum and challenged intravenously with P. yoelii 17XL asexual blood-stage parasites. Adsorption of immunogen and adjuvant to alum was optimized by adjusting buffer (phosphate versus acetate) and pH. We found that the adjuvant combination of ODN plus alum with yMSP1₁₉, injected intraperitoneally (i.p.), increased immunoglobulin G (IgG) yMSP1₁₉-specific antibody production 12-fold over Freund adjuvant given i.p., 3-fold over Freund adjuvant given subcutaneously (s.c.), 300-fold over alum given i.p., and 48-fold over alum given s.c. The predominant antibody isotype in the group receiving alum-ODN-yMSP1₁₉ was IgG1. Increased antibody levels correlated to protection from a challenge with P. yoelii 17XL. Supernatant cytokine levels of gamma interferon in yMSP1₁₉-stimulated splenocytes were dramatically elevated in the alum-ODN-yMSP1₁₉ group. Interleukin-10 (IL-10) levels were also elevated; however, no IL-5 was detected. The cytokine profile, as well as the predominant IgG1 antibody isotype, suggests the protective immune response was a mixed Th1/Th2 response.

Editor: W. A. Petri, Jr.

Present address: Viral Inc., San Diego, CA 92121-3088.

This article has been cited by other articles:

• Morefield, G. L., Hawkins, L. D., Ishizaka, S. T., Kissner, T. L., Ulrich, R. G. (2007). Synthetic Toll-Like Receptor 4 Agonist Enhances Vaccine Efficacy in an Experimental Model of Toxic Shock Syndrome. CVI 14: 1499-1504 [Abstract] [Full Text]  
• Jeamwattanalert, P., Mahakunkijcharoen, Y., Kittigul, L., Mahannop, P., Pichyangkul, S., Hirunpetcharat, C. (2007). Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 in Mice. CVI 14: 342-347 [Abstract] [Full Text]  
• Kumar, S., Jones, T. R., Oakley, M. S., Zheng, H., Kuppusamy, S. P., Taye, A., Krieg, A. M., Stowers, A. W., Kaslow, D. C., Hoffman, S. L. (2004). CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine. Infect. Immun. 72: 949-957 [Abstract] [Full Text]  
• Coban, C., Ishii, K. J., Stowers, A. W., Keister, D. B., Klinman, D. M., Kumar, N. (2004). Effect of CpG Oligodeoxynucleotides on the Immunogenicity of Pfs25, a Plasmodium falciparum Transmission-Blocking Vaccine Antigen. Infect. Immun. 72: 584-588 [Abstract] [Full Text]  
• Su, Z., Tam, M.-F., Jankovic, D., Stevenson, M. M. (2003). Vaccination with Novel Immunostimulatory Adjuvants against Blood-Stage Malaria in Mice. Infect. Immun. 71: 5178-5187 [Abstract] [Full Text]