Association of antibodies to Plasmodium falciparum merozoite surface protein-4 with protection against clinical malaria

Perraut, Ronald; Marie-Louise, Varela; Joos, Charlotte; Diouf, Babacar; Sokhna, Cheikh; Mbengué, Babacar; Tall, Adama; Loucoubar, Cheikh; Touré, Aissatou; Mercereau‐Puijalon, Odile

doi:10.1016/j.vaccine.2017.10.012

Cited by 22 publications

(28 citation statements)

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“…In Sudanese children aged over 5 years, a ** * ** ** * ** ** * ADRB activity < lower prevalence of IgG to MSP2 and MSP3 was found in MM, but levels of antibodies were comparable [51]. The use of baculovirus-expressed antigens which more faithfully reproduces conformational epitopes would appear to be an important factor for identifying relevant targets of protection-associated immunity [13,29,32]. The CM antibody responses to MSPs is highly variable in this study, possibly related to the urban setting with indeterminate individual episode chronology, the older (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Antibody responses to MSP1p19 has repeatedly been shown to be associated with clinical protection [52,53]. The use of baculovirus-expressed antigens which more faithfully reproduces conformational epitopes would appear to be an important factor for identifying relevant targets of protection-associated immunity [13,29,32]. Thus, the use of E. coli produced MSP1p19 by the Dodoo research team led to a negative association with protection [54] as opposed to more recent results using the baculovirus-derived version [13].…”

Section: Discussionmentioning

confidence: 99%

“…IgG/IgM responses were quantified by ELISA in duplicate plasma samples diluted 1 : 100, as previously described [21,23,29]. were considered seropositive for prevalence calculations [21,23,29,32]. Standards were included in each assay for plate comparability.…”

Section: Antigens and Enzyme-linked Immunosorbent Assay (Elisa) Procementioning

confidence: 99%

“…Sera showing an OD ratio > 2 corresponding to the signal of naive controls + 3 standard deviations (s.d.) were considered seropositive for prevalence calculations [21,23,29,32].…”

Section: Antigens and Enzyme-linked Immunosorbent Assay (Elisa) Procementioning

confidence: 99%

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Analysis of antibody responses to selected Plasmodium falciparum merozoite surface antigens in mild and cerebral malaria and associations with clinical outcomes

Mbengué

Fall

Varela

et al. 2019

Clinical and Experimental Immunology

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Merozoite surface proteins (MSPs) are critical for parasite invasion; they represent attractive targets for antibody-based protection against clinical malaria. To identify protection-associated target MSPs, the present study analysed antibody responses to whole merozoite extract (ME) and to defined MSP recombinant antigens in hospitalized patients from a low endemic urban area as a function of disease severity (mild versus cerebral malaria). Sera from 110 patients with confirmed severe cerebral malaria (CM) and 91 patients with mild malaria (MM) were analysed (mean age = 29 years) for total and subclass immunoglobulin (Ig)G to ME and total IgG to MSP1p19, MSP2, MSP3, MSP4 and MSP5 by enzyme-linked immunosorbent assay (ELISA). Functional antibody responses were evaluated using the antibody-dependent respiratory burst (ADRB) assay in a subset of sera. There was a trend towards higher IgG1 and IgG4 levels to ME in CM compared to MM; only ME IgM responses differed significantly between fatal and surviving CM patients. Increased prevalence of IgG to individual MSPs was found in the CM compared to the MM group, including significantly higher levels of IgG to MSP4 and MSP5 in the former. Sera from fatal (24·5%) versus surviving cases showed significantly lower IgG to MSP1p19 and MSP3 (P < 0·05). ADRB assay readouts correlated with high levels of anti-MSP IgG, and trended higher in sera from patients with surviving compared to fatal CM outcome (P = 0·07). These results document strong differential antibody responses to MSP antigens as targets of protective immunity against CM and in particular MSP1p19 and MSP3 as prognostic indicators.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Antigens and Enzyme-linked Immunosorbent Assay (Elisa) Procementioning

confidence: 99%

“…Sera showing an OD ratio > 2 corresponding to the signal of naive controls + 3 standard deviations (s.d.) were considered seropositive for prevalence calculations [21,23,29,32].…”

Section: Antigens and Enzyme-linked Immunosorbent Assay (Elisa) Procementioning

confidence: 99%

See 2 more Smart Citations

Analysis of antibody responses to selected Plasmodium falciparum merozoite surface antigens in mild and cerebral malaria and associations with clinical outcomes

Mbengué

Fall

Varela

et al. 2019

Clinical and Experimental Immunology

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“…This finding suggested that MSP4 is a potential malaria vaccine candidate, especially in combination with other antigens. MSP4 immunogenicity has been associated with protection in natural infections with P. falciparum [30][31][32]. In addition, MSP4 shows a high degree of conservation among P. falciparum isolates [16,33,34], supporting its potential consideration as a subunit component for malaria vaccine formulations.…”

mentioning

confidence: 94%

Immunogenicity analysis of conserved fragments in Plasmodium ovale species merozoite surface protein 4

Juliette

Chu

Kassegne

et al. 2020

Malar J

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Background There is an urgent need for an effective vaccine to control and eradicate malaria, one of the most serious global infectious diseases. Plasmodium merozoite surface protein 4 (MSP4) has been listed as a blood-stage subunit vaccine candidate for malaria. Infection with Plasmodium ovale species including P. ovale wallikeri and P. ovale curtisi, is also a source of malaria burden in tropical regions where it is sometimes mixed with other Plasmodium species. However, little is known about P. ovale MSP4. Methods The msp4 gene was amplified through polymerase chain reaction using genomic DNA extracted from blood samples of 46 patients infected with P. ovale spp. and amplified products were sequenced. Open reading frames predicted as immunogenic peptides consisting of 119 and 97 amino acids of P. ovale curtisi MSP4 (PocMSP4) and P. ovale wallikeri MSP4 (PowMSP4), respectively, were selected for protein expression. Recombinant proteins (rPoMSP4) were expressed in Escherichia coli, purified, analysed, and immunized in BALB/c mice. The specificity of anti-MSP4-immunoglobulin (Ig) G antibodies was evaluated by Western blot and enzyme-linked immunosorbent assays, and cellular immune responses were analysed via lymphocyte proliferation assays. Results Full peptide sequences of PocMSP4 and PowMSP4 were completely conserved in all clinical isolates, except in the epidermal growth factor-like domain at the carboxyl terminus where only one mutation was observed in one P. o. wallikeri isolate. Further, truncated PoMSP4 segments were successfully expressed and purified as ~ 32 kDa proteins. Importantly, high antibody responses with end-point titres ranging from 1:10,000 to 1:2,560,000 in all immunized mouse groups were observed, with high IgG avidity to PocMSP4 (80.5%) and PowMSP4 (92.3%). Furthermore, rPocMSP4 and rPowMSP4 cross-reacted with anti-PowMSP4-specific or anti-PocMSP4-specific antibodies. Additionally, anti-PoMSP4 IgG antibodies showed broad immuno-specificity in reacting against rPoMSP1 and rPoAMA1. Lastly, PocMSP4- and PowMSP4-immunized mice induced cellular immune responses with PocMSP4 (36%) and PowMSP4 cells (15.8%) during splenocyte proliferation assays. Conclusion Findings from this study suggest conservation in PoMSP4 protein sequences and high immunogenicity was observed in rPoMSP4. Furthermore, induction of immune responses in PocMSP4- and PowMSP4-immunized mice informed that both humoral and cellular immune responses play crucial roles for PoMSP4 in protection.

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Identification of Antibody Responses Predictive of Protection Against Clinical Malaria

Fonseca

Cordeiro

Sepúlveda

2022

Springer Proceedings in Mathematics &Amp; Statistics

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Association of antibodies to Plasmodium falciparum merozoite surface protein-4 with protection against clinical malaria

Cited by 22 publications

References 47 publications

Analysis of antibody responses to selected Plasmodium falciparum merozoite surface antigens in mild and cerebral malaria and associations with clinical outcomes

Analysis of antibody responses to selected Plasmodium falciparum merozoite surface antigens in mild and cerebral malaria and associations with clinical outcomes

Immunogenicity analysis of conserved fragments in Plasmodium ovale species merozoite surface protein 4

Identification of Antibody Responses Predictive of Protection Against Clinical Malaria

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