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Infection and Immunity, November 2004, p. 6300-6305, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6300-6305.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Strain-Specific Humoral Response to a Polymorphic Malaria Vaccine

Christian Flück,1 Tom Smith,1 Hans-Peter Beck,1 Andrea Irion,1 Inoni Betuela,2 Michael P. Alpers,2,3 Robin Anders,4 Allan Saul,5 Blaise Genton,1 and Ingrid Felger1*

Swiss Tropical Institute, Basel, Switzerland,1 Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea,2 Centre of International Health, Curtin University of Technology, Perth,3 Department of Biochemistry, La Trobe University, Victoria, Australia,4 Malaria Vaccine Development Unit, National Institutes of Health, Rockville, Maryland5

Received 5 April 2004/ Returned for modification 9 May 2004/ Accepted 1 August 2004

The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation.

* Corresponding author. Mailing address: Swiss Tropical Institute, Socinstrasse 57, P.O. Box CH-4002, Basel, Switzerland. Phone: 41-61-284 81 17. Fax: 41-61-271 86 54. E-mail: ingrid.felger{at}unibas.ch.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2004, p. 6300-6305, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6300-6305.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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