title: Ex vivo cytokine and memory T cell responses to the 42-kDa fragment of Plasmodium falciparum merozoite surface protein-1 in vaccinated volunteers.
abstract: A number of blood-stage malaria Ags are under development as vaccine candidates, but knowledge of the cellular responses to these vaccines in humans is limited. We evaluated the nature and specificity of cellular responses in healthy American volunteers vaccinated with a portion of the major merozoite surface protein-1 (MSP1) of Plasmodium falciparum, MSP1(42), formulated on Alhydrogel. Volunteers were vaccinated three times with 80 microg of either MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel. Cells collected 2 wk after the third vaccination produced Th1 cytokines, including IFN-gamma and IL-2 following Ag stimulation, and greater levels of the Th2 cytokines IL-5 and IL-13; the anti-inflammatory cytokine IL-10 and the molecule CD25 (IL-2Ralpha) were also detected. The volunteers were evaluated for the MSP1(42)-FVO or MSP1(42)-3D7 specificity of their T cell responses. Comparison of their responses to homologous and heterologous Ags showed ex vivo IFN-gamma and IL-5 levels that were significantly higher to homologous rather than to heterologous Ags. The epitopes involved in this stimulation were shown to be present in the dimorphic MSP1(33) portion of the larger MSP1(42)-3D7 polypeptide, and indirect experiment suggests the same for the MSP1(42)-FVO polypeptide. This contrasts with B cell responses, which were primarily directed to the conserved MSP1(19) portion. Furthermore, we explored the maturation of memory T cells and found that 46% of vaccinees showed specific memory T cells defined as CD4(+)CD45RO(+)CD40L(+) after long-term in vitro culture. The identification of human-specific CD4(+) memory T cells provides the foundation for future studies of these cells both after vaccination and in field studies.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Huaman
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.forename: Elissa
authors.initials: E
authors.lastname: Malkin
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mahanty
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
mesh_terms: D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; C527291:MSP1(42)-3D7 alhydrogel vaccine; C527290:MSP1(42)-FVO alhydrogel vaccine; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D016753:Interleukin-10; D007371:Interferon-gamma