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

Elizardez, Yelina Brito; Fotoran, Wesley Luzetti; Galisteo, Andre S. J.; Curado, Izilda; Kesper, Norival; Monteiro, Eliana Ferreira; Neto, Irineu Romero; Wunderlich, Gerd; Kirchgatter, Karin

doi:10.1371/journal.pone.0219629

Cited by 7 publications

(10 citation statements)

References 59 publications

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“…In the present study, we used five recombinant antigens derived from the MSP1 protein of this parasite species. The recombinant proteins were designed as GST-fusion proteins and successfully used with human sera in a previous epidemiological study [ 6 ]. With these five recombinant proteins of P. malariae MSP1 (PmMSP1 F1, PmMSP1 F2, PmMSP1 F3, PmMSP1 F4, PmMSP1 19 ), as well as with those of P. falciparum (PfMSP1 19 ) and P. vivax (PvMSP1 19 ), we found that about 40% of the NHP sera, from different areas in Brazil, were reactive to the recombinant antigens, with PmMSP1 F1 being the most frequently detected.…”

Section: Discussionmentioning

confidence: 99%

“…GST and GST-recombinant fusion proteins of PmMSP1 (PmMSP1 F1 , PmMSP1 F2 , PmMSP1 F3 , PmMSP1 F4 , PmMSP1 19 ), P. vivax (PvMSP1 19 ) and P. falciparum (PfMSP1 19 ), representing the polymorphic N-terminal (MSP1 F1 ), the central (MSP1 F2 , MSP1 F3 , MSP1 F4 ) and the conserved C-terminal (MSP1 19 ) regions [ 6 ], were used for detecting anti-parasite antibodies in the sera samples. The GST and GST-fusion proteins were purified on glutathione-Sepharose 4B (GE Healthcare, MilliporeSigma, St. Louis, MO, USA) and the protein concentration was determined with the Bradford protein Assay (Bio-Rad, Hercules, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The immunization of BALB/c mice with these recombinant proteins elicited a significant humoral immune response, making them potential component candidates for a vaccine against P. malariae. These recombinant proteins were also shown to be very useful as diagnostic markers in epidemiological studies and for the differential diagnosis of P. malariae infection [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Naturally Acquired Humoral Immunity against Malaria Parasites in Non-Human Primates from the Brazilian Amazon, Cerrado and Atlantic Forest

et al. 2020

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Non-human primates (NHPs) have been shown to be infected by parasites of the genus Plasmodium, the etiological agent of malaria in humans, creating potential risks of zoonotic transmission. Plasmodium brasilianum, a parasite species similar to P. malariae of humans, have been described in NHPs from Central and South America, including Brazil. The merozoite surface protein 1 (MSP1), besides being a malaria vaccine candidate, is highly immunogenic. Due to such properties, we tested this protein for the diagnosis of parasite infection. We used recombinant proteins of P. malariae MSP1, as well as of P. falciparum and P. vivax, for the detection of antibodies anti-MSP1 of these parasite species, in the sera of NHPs collected in different regions of Brazil. About 40% of the NHP sera were confirmed as reactive to the proteins of one or more parasite species. A relatively higher number of reactive sera was found in animals from the Atlantic Forest than those from the Amazon region, possibly reflecting the former more intense parasite circulation among NHPs due to their proximity to humans at a higher populational density. The presence of Plasmodium positive NHPs in the surveyed areas, being therefore potential parasite reservoirs, needs to be considered in any malaria surveillance program.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Naturally Acquired Humoral Immunity against Malaria Parasites in Non-Human Primates from the Brazilian Amazon, Cerrado and Atlantic Forest

et al. 2020

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“…For example, the recognition of PmMSP1 19 was evaluated by ELISA using serum from Brazilian individuals diagnosed with malaria due to Pm (n = 16) in parallel with sera from patients with unrelated diseases (n = 21), or healthy donors (n = 15), reaching 100% sensitivity and specificity. On the other hand, sera from Pv or Pfinfected individuals did not react at all against recombinant PmMSP1 19 protein (Elizardez et al, 2019). All three MSP1 19 antigens (Pf, Pv and Pm) were recently used as bound-antigens in ELISA assays that were performed to evaluate the seroprevalence of these Plasmodium species in Suriname (Labadie-Bracho et al, 2020).…”

Section: Rdt Typesmentioning

confidence: 99%

Diagnostic Methods for Non-Falciparum Malaria

Gimenez

Marques

Regiart

et al. 2021

Front. Cell. Infect. Microbiol.

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Malaria is a serious public health problem that affects mostly the poorest countries in the world, killing more than 400,000 people per year, mainly children under 5 years old. Among the control and prevention strategies, the differential diagnosis of the Plasmodium–infecting species is an important factor for selecting a treatment and, consequently, for preventing the spread of the disease. One of the main difficulties for the detection of a specific Plasmodium sp is that most of the existing methods for malaria diagnosis focus on detecting P. falciparum. Thus, in many cases, the diagnostic methods neglect the other non-falciparum species and underestimate their prevalence and severity. Traditional methods for diagnosing malaria may present low specificity or sensitivity to non-falciparum spp. Therefore, there is high demand for new alternative methods able to differentiate Plasmodium species in a faster, cheaper and easier manner to execute. This review details the classical procedures and new perspectives of diagnostic methods for malaria non-falciparum differential detection and the possibilities of their application in different circumstances.

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“…of different infectious and parasitic diseases, that GST-tagged recombinant antigens have comparable cross-reactivity, specificity and antigenicity compared with untagged antigens, (e.g. [23][24][25][26][27][28][29][30]). In accordance, the specificity of the GST-tagged 2B2t recombinant antigen was actually higher than the specificity of the non-tagged 2B2t antigen (95.8% vs. 77.8%), and the cross-reactivity with sera from patients with AE was lower for the GST-2B2t compared with the 2B2t antigen (38.7% vs. 44%).…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis

et al. 2020

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Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2–91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1–76.2), 2B2t (65.5%, 95% CI: 58.5–72.0), GST-Ag5t (64.5%, 95% CI: 57.5–71.1) and GST-DIPOL (63.1%, 95% CI: 56.0–69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3–99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6–50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.

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

Cited by 7 publications

References 59 publications

Naturally Acquired Humoral Immunity against Malaria Parasites in Non-Human Primates from the Brazilian Amazon, Cerrado and Atlantic Forest

Naturally Acquired Humoral Immunity against Malaria Parasites in Non-Human Primates from the Brazilian Amazon, Cerrado and Atlantic Forest

Diagnostic Methods for Non-Falciparum Malaria

Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis

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