Personal information collected in this study was kept confidential. Consent for publicationNot applicable. Competing interestsThe authors declare that they have no competing interests. Footnotes Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.. Both cross-sectional and cohort studies were used to explore the development and persistence of long-lived antibody and memory B cell responses to PvRBP1a in individuals who lived in an area of low malaria endemicity. Antibody titers and frequency of memory B cells specific to PvRBP1a were measured during contamination and following recovery for up to 12?months. Results IgG antibody responses against PvRBP1a were prevalent during acute vivax malaria, predominantly IgG1 subclass responses. High responders to PvRBP1a had persistent antibody responses for at least 12-month post-infection. Further analysis of high responder found a direct relation between antibody titers and frequency of activated and atypical memory B cells. Furthermore, circulating antibody secreting cells and memory B cells specific to PvRBP1a were generated during contamination. The PvRBP1a-specific memory B cells were maintained for up to 3-12 months post-infection, indicating the ability of PvRBP1a to induce long-term humoral immunity. Conclusion The study revealed an ability of PvRBP1a protein to induce the generation and maintenance of antibody and memory B cell responses. Therefore, PvRBP1a could be considered as a vaccine candidate against the blood-stage of is one of the most prevalent malarial species in the world, found especially in Asia and the Americas [2]. Treatment and control of have become serious challenges due to drug and vector resistance, wide distribution, antigen variation, relapsing biology and frequent co-infection with [3]. Moreover, naturally acquired immune responses to are short-lived and biased toward strain-specific immunity [4, 5]. Given these factors, a prophylactic vaccine would add an important tool in strategies to prevent and eliminate malaria. Blood-stages of the life cycle of are responsible for the clinical symptoms associated with the contamination. Therefore, a vaccine against this stage would reduce parasite load and clinical severity. Several blood-stage antigens that are expressed on merozoites play crucial roles during the invasion of red blood cells (RBCs) and are attractive targets for an effective vaccine [6, 7]. One of the leading blood-stage vaccine candidates is usually duffy binding protein (PvDBP), a parasite cell surface protein in the erythrocyte binding-like (EBL) invasion protein family [8, 9]. This protein binds to the duffy antigen receptor for chemokines (DARC), a receptor on the surface of the erythrocyte [10]. There are individuals with naturally acquired immunity who possess anti-DBP antibodies that inhibit the DBP-DARC conversation and appear to neutralize invasion [11]. However, recent studies reported that Duffy-negative individuals are involved in contamination, indicating the presence of an alternative pathway of invasion [12, 13]. Therefore, finding new vaccine candidates with distinct target antigens is necessary. The Linifanib (ABT-869) reticulocyte binding protein (PvRBP) family is usually a group of merozoite proteins that play an important role in parasite invasion of RBCs [14]. It is composed of 11 members, encoded in five full-length genes (RBP and Py235 members [15, Linifanib (ABT-869) 16]. Among of them, PvRBP1a is proposed as a blood-stage vaccine candidate as it forms a complex and binds Mouse monoclonal antibody to PYK2. This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-inducedregulation of ion channels and activation of the map kinase signaling pathway. The encodedprotein may represent an important signaling intermediate between neuropeptide-activatedreceptors or neurotransmitters that increase calcium flux and the downstream signals thatregulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation andactivation in response to increases in the intracellular calcium concentration, nicotinicacetylcholine receptor activation, membrane depolarization, or protein kinase C activation. Thisprotein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulatorassociated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of theFAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinasesfrom other subfamilies. Four transcript variants encoding two different isoforms have been foundfor this gene specifically to reticulocytes. However, its cognate receptors remain to be tested further by finding the key receptor-ligand interactions that mediate host cell invasion [17]. Antigenicity of PvRBP1a has been Linifanib (ABT-869) shown in mice as immunization stimulated high-titer antibody responses [18, 19]. In patients, high rates of positivity for anti-PvRBP1a are reported in natural contamination in Papua New Guinea (PNG), Brazil, India and Thailand [19C24]. Previous studies, focusing on IgG antibody profiling, revealed that cytophilic IgG1 and IgG3 are the predominant antibody subclasses in responses to PvRBP1a antigen [21, 24]. These cytophilic antibodies against PvRBP1a may contribute to protection against clinical malaria in a high transmission area of PNG [21]. Moreover, natural human antibodies against PvRBP1a have been shown to inhibit merozoite invasion of reticulocytes [19, 23]. Altogether, PvRBP1a might be a promising candidate as a vaccine against patients. Cross-sectional and longitudinal studies were conducted to determine anti-PvRBP1a IgG and IgG subclass levels, and to assess correlation with frequency of memory B cell (MBC) subsets and plasma cells. The development of antibody secreting cells (ASCs) and long-lived MBCs specific to PvRBP1a was evaluated during and after malaria contamination. A better understanding of the.
Personal information collected in this study was kept confidential