Recombinant proteins of Plasmodium malariae merozoite surface protein 1 (PmMSP1): Testing immunogenicity in the BALB/c model and potential use as diagnostic tool.

Yelina B Elizardez,Irineu Romero Neto,Wesley L Fotoran,Gerhard Wunderlich,Karin Kirchgatter,Eliana F Monteiro,Norival Kesper Junior,Izilda Curado,Andrés J Galisteo Junior,Takafumi Tsuboi

doi:10.1371/journal.pone.0219629

Yelina B Elizardez, Irineu Romero Neto + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0219629

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Journal: PloS one	Publication Date: Jul 25, 2019
Citations: 8	License type: CC BY 4.0

Affiliation: Universidade de São Paulo

Abstract

BackgroundPlasmodium malariae is the third most prevalent human malaria-causing species and has a patchy, but ample distribution in the world. Humans can host the parasite for years without presenting significant symptoms, turning its diagnosis and control into a difficult task. Here, we investigated the immunogenicity of recombinant proteins of P. malariae MSP1.MethodsFive regions of PmMSP1 were expressed in Escherichia coli as GST-fusion proteins and immunized in BALB/c mice. The specificity, subtyping, and affinity of raised antibodies were evaluated by enzyme-linked immunosorbent assays. Cellular immune responses were analyzed by lymphoproliferation assays and cytokine levels produced by splenocytes were detected by cytometry.ResultsWe found that N-terminal, central regions, and PmMSP119 are strongly immunogenic in mice. After three doses, the induced immune responses remained high for 70 days. While antibodies induced after immunization with N-terminal and central regions showed similar affinities to the target antigens, affinities of IgG against PmMSP119 were higher. All proteins induced similar antibody subclass patterns (predominantly IgG1, IgG2a, and IgG2b), characterizing a mixed Th1/Th2 response. Further, autologous stimulation of splenocytes from immunized mice led to the secretion of IL2 and IL4, independently of the antigen used. Importantly, IgG from P. malariae-exposed individuals reacted against PmMSP1 recombinant proteins with a high specificity. On the other hand, sera from P. vivax or P. falciparum-infected individuals did not react at all against recombinant PmMSP1 proteins.ConclusionRecombinant PmMSP1 proteins are very useful diagnostic markers of P. malariae in epidemiological studies or in the differential diagnosis of malaria caused by this species. Immunization with recombinant PmMSP1 proteins resulted in a significant humoral immune response, which may turn them potential component candidates for a vaccine against P. malariae.

Highlights

Plasmodium malariae was the first malaria parasite observed in 1881 by Charles Laveran, Nobel Prize winner for discovering the cause of malaria [1]
We found that N-terminal, central regions, and PmMSP119 are strongly immunogenic in mice
Immunization with recombinant PmMSP1 proteins resulted in a significant humoral immune response, which may turn them potential component candidates for a vaccine against P. malariae

Summary

Introduction

Plasmodium malariae was the first malaria parasite observed in 1881 by Charles Laveran, Nobel Prize winner for discovering the cause of malaria [1]. In South America, P. malariae is associated with zoonotic infections, and is confounded with P. brasilianum, a parasite that infects twelve different genera of New World primates [1]. These and humans have high levels of seropositivity for P. malariae and P. brasilianum antigens in endemic areas [2]. Parasitemias in P. malariae infections are usually low compared to those in patients infected with P. falciparum or P. vivax perhaps due to its longer developmental cycle (72 h for P. malariae versus 48 h for P. vivax and P. falciparum), lower number of merozoites produced per erythrocyte cycle, and its preference for developing in older erythrocytes [2]. We investigated the immunogenicity of recombinant proteins of P. malariae MSP1

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