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Infection and Immunity, April 2000, p. 2102-2109, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Linkage of Exogenous T-cell Epitopes to the 19-Kilodalton Region of Plasmodium yoelii Merozoite Surface Protein 1 (MSP119) Can Enhance Protective Immunity against Malaria and Modulate the Immunoglobulin Subclass Response to MSP119

Niklas Ahlborg,1,dagger Irene T. Ling,2 Anthony A. Holder,2 and Eleanor M. Riley1,*

Institute of Cell, Animal and Population Biology, Edinburgh University, Edinburgh EH9 3JT,1 and National Institute for Medical Research, Mill Hill, London NW7 1AA,2 United Kingdom

Received 17 August 1999/Returned for modification 8 October 1999/Accepted 11 January 2000

The degree of protection against Plasmodium yoelii asexual blood stages induced by immunization of mice with the 19-kDa region of merozoite surface protein 1 (MSP119) is H-2 dependent. As a strategy to improve the protection, mouse strains with disparate H-2 haplotypes were immunized with glutathione S-transferase (GST)-MSP119 proteins including either a universal T-cell epitope from tetanus toxin (P2) or an I-Ak-restricted T-cell epitope (P8) from Plasmodium falciparum Pf332. In H-2k mice which are poorly protected following immunization with GST-MSP119, GST-P2-MSP119 significantly improved the protection. In mice partially (H-2k/b) or well protected by GST-MSP119 (H-2d and H-2b), P2 did not further increase the protection. However, the protection of H-2k/b mice and to some extent H-2k mice was improved by immunization with GST-P8-MSP119. The magnitudes of immunoglobulin G1 (IgG1) and IgG2a responses in mice immunized with the GST-MSP119 variants correlated with low peak parasitemia, indicating a protective capacity of these IgG subclasses. In H-2k mice immunized with GST-P2-MSP119, both IgG1 and IgG2a responses were significantly enhanced. The epitope P2 appeared to have a general ability to modulate the IgG subclass response since all four mouse strains displayed elevated IgG2a and/or IgG2b levels after immunization with GST-P2-MSP119. In contrast, GST-P8-MSP119 induced a slight enhancement of IgG responses in H-2k/b and H-2k mice without any major shift in IgG subclass patterns. The ability to improve the protective immunity elicited by P. yoelii MSP119 may have implications for improvement of human vaccines based on P. falciparum MSP119.

* Corresponding author. Mailing address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, United Kingdom. Phone: 44-171-927 2706. Fax: 44-171-637 4314. E-mail: e.riley{at}lshtm.ac.uk.

dagger Present address: MABTECH AB, S-13137 Nacka, Sweden.

Infection and Immunity, April 2000, p. 2102-2109, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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