Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

Abstract

BackgroundPlasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.MethodsThe study was carried out in Paragominas, Pará State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-γ and IL-10 were measured by enzyme-linked immunosorbent assay.ResultsThe prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-γ and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient’s cells while low levels of IFN-γ and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG subclass.PvMSP-119-induced antibodies were predominantly on non-cytophilic subclasses.ConclusionsThe results presented here shows that PvMSP-119 was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-119 in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.

Immunogenicity of the Plasmodium vivax merozoite surface protein 1 paralog in the induction of naturally acquired antibody and memory B cell responses

“…It is possible to acquire immunity against blood stage antigens in natural exposure-derived P. vivax infections. Similarly, protection against P. vivax infection could be induced by numerous immunization strategies [ 7 ]. However, the rapid mutation of the blood-stage antigens is the primary challenging problem in its vaccine development.…”

Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area

“…In this scenario, studies assessing the immune response against Plasmodium falciparum vaccine candidates in naturally exposed individuals from the Brazilian Amazon were conducted by our group. 10,[18][19][20][21][22] In Brazil, malaria is hypo-to meso-endemic, present throughout the year with clear seasonal fluctuations and is frequently associated with migration movements of nonimmune individuals to areas where malaria is endemic. 23 The exposed populations are composed of autochthonous and migrant individuals from the nonendemic regions of Brazil.…”

Frequency ofTNFA,INFG, andIL10Gene Polymorphisms and Their Association with MalariaVivaxand Genomic Ancestry

“…IFN- γ , TNF- α , IL-6, IL-12, IL-1 β , and IL-8 are reported at higher levels in individuals infected with Plasmodium than in controls or in individuals with severe malaria [21, 24, 25]. However, contradictory results have also been observed, with lower levels of these cytokines reported in infected patients [25, 26]. …”