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Dissertation
Characterization of humoral immune responses directed to the epidermal growth factor-like-domains of the merozoite surface protein-1 from Plasmodium yoelii yoelii 17XL
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
Jul 1996
DOI:
https://doi.org/10.17918/00007666
Abstract
The merozoite surface protein-1 (MSP-1) is a leading candidate for a vaccine targeted at the erythrocytic stages of malarial parasite development. Recently, there has been increasing interest in this polypeptide, particularly in the carboxyl-terminal EGF-like domains. We have previously shown that this region from the rodent model Plasmodium yoelii, when expressed in native configuration, could immunize mice against an otherwise lethal challenge infection. In this model system, protection appears predominantly mediated by antibodies. In all rodent immunization studies to date, however, the immunogen has contained both of the postulated EGF-like domains. Firstly, we report on the efficacy of immunization with the individual EGF-like domains from P. yoelii in elicitation of a protective host response. Although all animals developed some level of antibody in response to the various immunogens, only those animals immunized with both EGF-like domains produced antibodies which could recognize the native MSP-1 molecule. Antibodies generated against the individual EGF-like domains did cross-react with the double EGF-like domain structure, suggesting the immunogens had retained elements of native configuration. In addition, only those animals which generated antibodies capable of recognizing native MSP-1 showed any level of protection from challenge infection. Secondly, through the characterization of protective versus non-protective animals, we report on criteria of humoral immunity which appear to correlate with in vivo protection. Using variably protected mice which differed only in their major histocompatibility complex haplotypes, we demonstrate that antibodies having high avidity and titer, with the correct specificity, in response to both EGF-like domains, positively correlate with protection. In particular, these characteristics associated with antibodies generated against the double-EGF-like domain structure, as opposed to either of the individual domains alone displayed the most significant correlation with in vivo protection. These results, taken together, suggest that determinants unique to the double EGF-like domain structure may be necessary for the generation of antibodies specific for the native configuration of MSP-1, and that these antibodies play a significant role in protection.
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Details
- Title
- Characterization of humoral immune responses directed to the epidermal growth factor-like-domains of the merozoite surface protein-1 from Plasmodium yoelii yoelii 17XL
- Creators
- Paul Anthony Calvo
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- xii, 150 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology [Historical]; Allegheny University of the Health Sciences (1996-1998); School of Medicine (1996-1998)
- Other Identifier
- 991021888910204721