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Infection and Immunity, December 2003, p. 6766-6774, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6766-6774.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Biochemical and Immunological Characterization of Bacterially Expressed and Refolded Plasmodium falciparum 42-Kilodalton C-Terminal Merozoite Surface Protein 1

Sanjay Singh,* Michael C. Kennedy, Carole A. Long, Allan J. Saul, Louis H. Miller, and Anthony W. Stowers*

Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville Maryland 20852

Received 12 February 2003/ Returned for modification 24 April 2003/ Accepted 3 September 2003

Protection against Plasmodium falciparum can be induced by vaccination in animal models with merozoite surface protein 1 (MSP1), which makes this protein an attractive vaccine candidate for malaria. In an attempt to produce a product that is easily scaleable and inexpensive, we expressed the C-terminal 42 kDa of MSP1 (MSP142) in Escherichia coli, refolded the protein to its native form from insoluble inclusion bodies, and tested its ability to elicit antibodies with in vitro and in vivo activities. Biochemical, biophysical, and immunological characterization confirmed that refolded E. coli MSP142 was homogeneous and highly immunogenic. In a formulation suitable for human use, rabbit antibodies were raised against refolded E. coli MSP142 and tested in vitro in a P. falciparum growth invasion assay. The antibodies inhibited the growth of parasites expressing either homologous or heterologous forms of P. falciparum MSP142. However, the inhibitory activity was primarily a consequence of antibodies directed against the C- terminal 19 kDa of MSP1 (MSP119). Vaccination of nonhuman primates with E. coli MSP142 in Freund's adjuvant protected six of seven Aotus monkeys from virulent infection with P. falciparum. The protection correlated with antibody-dependent mechanisms. Thus, this new construct, E. coli MSP142, is a viable candidate for human vaccine trials.

* Corresponding author. Mailing address for Sanjay Singh: Malaria Vaccine Development Unit, NIAID/NIH, Bldg. TW1, Rm. 1210A, 5640 Fisher Lane, Rockville, MD 20852. Phone: (301) 435-2917. Fax: (301) 480-1962. E-mail: ssingh{at}niaid.nih.gov. Present address for Anthony W. Stowers: CSL Ltd., 45 Poplar Rd., Parkville, Victoria 3052, Australia. Phone: 61-3-9389-1911. Fax: 61-3-9389-1434. E-mail: anthony.stowers{at}csl.com.au.

Editor: J. M. Mansfield

Infection and Immunity, December 2003, p. 6766-6774, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6766-6774.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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