The murine malarial parasite P. yoelii 17X is a model system which clearly requires the production of antibody by the infected host for resolution of infection. We have constructed a monoclonal antibody (McAb 302) which provides dramatic protection from a lethal P. yoelii 17XL challenge, even in the antibody is given after infection. We propose to use this antibody as a probe to investigate a number of aspects of the murine humoral response to malarial infection. Our primary studies will involve determining the biological role of the idiotype represented by McAb 302. This will be approached by the generation of anti-idiotypic antibody to the 302 idiotype, leading to the development of a specific 302 idiotype assay. This assay will be used to compare the kinetics of appearance and concentration of these antibodies in a variety of protective and nonprotective sera. The in vivo regulatory role of anti-idiotypic antibodies will be explored by passive transfer of anti-idiotypic antibody. We also propose to examine the possible role of the unusual IgG3 isotype in the biological activity of McAb 302. Finally, we will isolate and study the major 230kd plasmodial antigen recognized by this antibody with particular attention to identification of significant epitopes. These studies will define more critically the biological role of antibodies to a protective plasmodial molecule and particularly those antibodies of the 302 idiotype. If the constraints are severe on the idiotype, isotype, or concentration of antibodies that must be attained to give protection, then this has significant consequences for human vaccination programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI021089-01A1
Application #
3131041
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Hahnemann University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
Rotman, H L; Daly, T M; Long, C A (1999) Plasmodium: immunization with carboxyl-terminal regions of MSP-1 protects against homologous but not heterologous blood-stage parasite challenge. Exp Parasitol 91:78-85
Kang, Y; Calvo, P A; Daly, T M et al. (1998) Comparison of humoral immune responses elicited by DNA and protein vaccines based on merozoite surface protein-1 from Plasmodium yoelii, a rodent malaria parasite. J Immunol 161:4211-9
Rotman, H L; Daly, T M; Clynes, R et al. (1998) Fc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model. J Immunol 161:1908-12
Daly, T M; Long, C A (1996) Influence of adjuvants on protection induced by a recombinant fusion protein against malarial infection. Infect Immun 64:2602-8
Calvo, P A; Daly, T M; Long, C A (1996) Plasmodium yoelii: the role of the individual epidermal growth factor-like domains of the merozoite surface protein-1 in protection from malaria. Exp Parasitol 82:54-64
Farley, P J; Long, C A (1995) Plasmodium yoelii yoelii 17XL MSP-1: fine-specificity mapping of a discontinuous, disulfide-dependent epitope recognized by a protective monoclonal antibody using expression PCR (E-PCR). Exp Parasitol 80:328-32
Kang, Y; Long, C A (1995) Sequence heterogeneity of the C-terminal, Cys-rich region of the merozoite surface protein-1 (MSP-1) in field samples of Plasmodium falciparum. Mol Biochem Parasitol 73:103-10
Daly, T M; Long, C A (1995) Humoral response to a carboxyl-terminal region of the merozoite surface protein-1 plays a predominant role in controlling blood-stage infection in rodent malaria. J Immunol 155:236-43
Farley, P J; Srivastava, R; Long, C A (1994) Sequence of the gene encoding the N-terminal portion of the Plasmodium yoelii yoelii 17XL merozoite surface protein-1 (MSP-1). Gene 151:335-6
Nussenzweig, R S; Long, C A (1994) Malaria vaccines: multiple targets. Science 265:1381-3

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