Journal article
Suppression of lethal Plasmodium yoelii malaria following protective immunization requires antibody-, IL-4, and IFN-gamma-dependent responses induced by vaccination and/or challenge infection
The Journal of immunology (1950), v 180(1), pp 444-453
01 Jan 2008
PMID: 18097046
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Immunization with Plasmodium yoelii merozoite surface protein (PyMSP)-8 protects mice from lethal malaria but does not prevent infection. Using this merozoite surface protein-based vaccine model, we investigated vaccine- and infection-induced immune responses that contribute to protection. Analysis of prechallenge sera from rPyMSP-8-immunized C57BL/6 and BALB/c mice revealed high and comparable levels of Ag-specific IgG, but differences in isotype profile and specificity for conformational epitopes were noted. As both strains of mice were similarly protected against P. yoelii, we could not correlate vaccine-induced responses with protection. However, passive immunization studies suggested that protection resulted from differing immune responses. Studies with cytokine-deficient mice showed that protection was induced by immunization of C57BL/6 mice only when IL-4 and IFN-gamma were both present. In BALB/c mice, the absence of either IL-4 or IFN-gamma led to predictable shifts in the IgG isotype profile but did not reduce the magnitude of the Ab response induced by rPyMSP-8 immunization. Immunized IL-4(-/-) BALB/c mice were solidly protected against P. yoelii. To our surprise, immunized IFN-gamma(-/-) BALB/c mice initially controlled parasite growth but eventually succumbed to infection. Analysis of cytokine production revealed that P. yoelii infection induced two distinct peaks of IFN-gamma that correlated with periods of controlled parasite growth in intact, rPyMSP-8-immunized BALB/c mice. Maximal parasite growth occurred during a period of sustained TGF-beta production. Combined, the data indicate that induction of protective responses by merozoite surface protein-based vaccines depends on IL-4 and IFN-gamma-dependent pathways and that vaccine efficacy is significantly influenced by host responses elicited upon infection.
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Details
- Title
- Suppression of lethal Plasmodium yoelii malaria following protective immunization requires antibody-, IL-4, and IFN-gamma-dependent responses induced by vaccination and/or challenge infection
- Creators
- Patricia M. Petritus - Drexel UniversityJames M. Burns - Drexel University
- Publication Details
- The Journal of immunology (1950), v 180(1), pp 444-453
- Publisher
- American Association of Immunologists
- Number of pages
- 10
- Grant note
- R01AI035661 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01AI35661 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000252162700052
- Scopus ID
- 2-s2.0-40449140820
- Other Identifier
- 991019168130104721
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- Web of Science research areas
- Immunology