title: Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry-Associated Membrane Antigen.
abstract: Rhoptry-associated membrane antigen (RAMA) is an abundant glycophosphatidylinositol (GPI)-anchored protein that is embedded within the lipid bilayer and is implicated in parasite invasion. Antibody responses against rhoptry proteins are produced by individuals living in a malaria-endemic area, suggesting the immunogenicity of Plasmodium vivax RAMA (PvRAMA) for induction of immune responses during P. vivax infection. To determine whether PvRAMA contributes to the acquisition of immunity to malaria and could be a rational candidate for a vaccine, the presence of memory T cells and the stability of the antibody response against PvRAMA were evaluated in P. vivax-exposed individuals. The immunogenicity of PvRAMA for the induction of T cell responses was evaluated by in vitro stimulation of peripheral blood mononuclear cells (PBMCs). High levels of interferon (IFN)-γ and interleukin (IL)-10 cytokines were detected in the culture supernatant of PBMCs, and the CD4+ T cells predominantly produced IL-10 cytokine. The levels of total anti-PvRAMA immunoglobulin G (IgG) antibody were significantly elevated, and these antibodies persisted over the 12 months of the study. Interestingly, IgG1, IgG2 and IgG3 were the major antibody subtypes in the response to PvRAMA. The frequency of IgG3 in specific to PvRAMA antigen maintained over 12 months. These data could explain the immunogenicity of PvRAMA antigen in induction of both cell-mediated and antibody-mediated immunity in natural P. vivax infection, in which IFN-γ helps antibody class switching toward the IgG1, IgG2 and IgG3 isotypes and IL-10 supports PvRAMA-specific antibody production.
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
authors.forename: Siriruk
authors.initials: S
authors.lastname: Changrob
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.|Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.
authors.forename: Seong-Kyun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Republic of Korea.|Department of Medical Research, Yangon, Myanmar.
authors.forename: Myat Htut
authors.initials: MH
authors.lastname: Nyunt
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Korea University Guro Hospital, Guro Gu, Seoul, Republic of Korea.
authors.forename: Chae Seung
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Division of Malaria Research Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
authors.forename: Patchanee
authors.initials: P
authors.lastname: Chootong
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D055550:Protein Stability; D015800:Protozoan Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C065352:rhoptry associated protein, Plasmodium; D016753:Interleukin-10; D007371:Interferon-gamma