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.
Highlights
One of the major global public health problems is malaria, a life-threatening blood disease caused by the Plasmodium parasite, which is transmitted to humans by female Anopheles mosquitoes
The IFN-γ concentrations produced by Plasmodium vivax Rhoptry-associated membrane antigen (RAMA) (PvRAMA)-stimulated peripheral blood mononuclear cells (PBMCs) from patients who had recovered from P. vivax infection were significantly higher than those produced by unstimulated control cells (PvRAMA = 72.45 ± 80.07 pg/ml, unstimulated = 13.59 ± 22.53 pg/ml, P = 0.0078, Fig 1)
A significantly higher level of production of IFN-γ and IL-10 induced by PvRAMA antigen stimulation of PBMCs was observed in PBMC cultures from P. vivax-recovered subjects
Summary
One of the major global public health problems is malaria, a life-threatening blood disease caused by the Plasmodium parasite, which is transmitted to humans by female Anopheles mosquitoes. Because the number of reports of P. vivax resistance to first-line antimalarial drug treatment has significantly increased, research into the development of a vaccine is considered be an important approach to blocking malaria transmission [3]. Evidence from both immunization experiments in animals and from human studies has suggested the possibility of vaccination against malaria [4,5,6,7,8]. To evaluate PvRAMA antigen as a vaccine candidate, its ability to elicit an immune response, including the development of memory T cells and specific antibody against PvRAMA, and the stability of the anti-PvRAMA antibody response were assessed in P. vivaxexposed individuals from malaria-endemic areas
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