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.

Plasmodium vivax transcriptional profiling of low input cryopreserved isolates through the intraerythrocytic development cycle

“…In terms of invasion ligand expression, though there is notable variation within an isolate, we find highly antigenic ligands, such as MSP1, MSP9, MSA180 and RAMA, are most highly expressed, which is encouraging because each of these is also being considered for vaccine development [41][42][43]. It is important to note, however, that while there is marked differences in invasion ligand expression between the isolates, an unknown portion of this variation is likely explained by the differences in the maturity of the schizonts, making it difficult to compare across biological replicates.…”

An Overview of Peripheral Blood Mononuclear Cells as a Model for Immunological Research of Toxoplasma gondii and Other Apicomplexan Parasites

“…One of the most studied apicomplexan parasites is Plasmodium , the pathogen that causes malaria, one of the most important public health problems worldwide. Nearly all studies regarding this parasite that have used PBMCs have focused on the development of vaccine candidates, particularly those using the peptide polling scheme (Anum et al, 2015; Ganeshan et al, 2016; Mensah et al, 2016) or recombinant proteins (Garraud et al, 2002; Garg et al, 2008; Gitau et al, 2014; Changrob et al, 2016). These studies have shown that, when PBMCs are challenged with molecules derived from Plasmodium , the immune response is characterized by Th1 cytokines such as IFN-γ, IL-1β, and TNF-α.…”

The persistence of naturally acquired antibodies and memory B cells specific to rhoptry proteins of Plasmodium vivax in patients from areas of low malaria transmission

“…The rhoptry neck protein of merozoites, PvRALP1, triggers IgG3, IgG2 and IgG1 isotype responses in P. vivax -exposed Korean individuals, and purified serum anti-PfRALP1 from Malian P. falciparum -infected patients inhibits parasite invasion [30, 35]. Two P. vivax proteins at the rhoptry bulb, rhoptry-associated membrane protein (RAMA) and RhopH2 antigens, show an ability to induce the acquisition of humoral immunity in both mouse models and patients [33, 38]. Interestingly, the anti-PvRAMA response is maintained up to 9 months after anti-malarial treatment, and some patients maintain antibody responses up to 12 months post-infection [38].…”

“…Two P. vivax proteins at the rhoptry bulb, rhoptry-associated membrane protein (RAMA) and RhopH2 antigens, show an ability to induce the acquisition of humoral immunity in both mouse models and patients [33, 38]. Interestingly, the anti-PvRAMA response is maintained up to 9 months after anti-malarial treatment, and some patients maintain antibody responses up to 12 months post-infection [38]. All of these data indicate that the combination of these rhoptry proteins with other blood-stage proteins in a vaccine design may induce protective responses of humoral immunity.…”