Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

Costa, Joana D'Arc Neves; Zanchi, Fernando Berton; Rodrigues, Francisco Lurdevanhe da Silva; Honda, Eduardo Rezende; Katsuragawa, Tony Hiroshi; Pereira, Dhélio Batista; Taborda, Roger Lafontaine Mesquita; Tada, Mauro Shugiro; Ferreira, Ricardo de Godoi Mattos; Pereira-da-Silva, Luiz Hildebrando

doi:10.1590/s0074-02762013000100016

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…This suggests that some Pf and Pv orthologs may share linear or conformational epitopes that elicit cross-reactive antibodies able to protect against symptomatic Pf, Pv, or Pf/Pv infections. Naturally-acquired crossreactive antibody responses to MSP5 (75) and CLAG9 (76) have been observed in other endemic settings. Alternatively, it is possible that these apparent cross-reactive responses do not stem from shared epitopes between P. vivax and P. falciparum orthologous proteins, but instead could result from previous infections with the other Plasmodium species.…”

Section: S)mentioning

confidence: 85%

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Finney

Danziger

Molina

et al. 2014

Molecular & Cellular Proteomics

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Malaria remains one of the most prevalent and lethal human infectious diseases worldwide. A comprehensive characterization of antibody responses to blood stage malaria is essential to support the development of future vaccines, sero-diagnostic tests, and sero-surveillance methods. We constructed a proteome array containing 4441 recombinant proteins expressed by the blood stages of the two most common human malaria parasites, P. falciparum (Pf) and P. vivax (Pv), and used this array to screen sera of Papua New Guinea children infected with Pf, Pv, or both (Pf/Pv) that were either symptomatic (febrile), or asymptomatic but had parasitemia detectable via microscopy or PCR. We hypothesized that asymptomatic children would develop antigen-specific antibody profiles associated with antidisease immunity, as compared with symptomatic children. The sera from these children recognized hundreds of the arrayed recombinant Pf and Pv proteins. In general, responses in asymptomatic children were highest in those with high parasitemia, suggesting that antibody levels are associated with parasite burden. In contrast, symptomatic children carried fewer antibodies than asymptomatic children with infections detectable by microscopy, particularly in Pv and Pf/Pv groups, suggesting that antibody production may be impaired during symptomatic infections. We used machine-learning algorithms to investigate the relationship between antibody responses and symptoms, and we identified antibody responses to sets of Plasmodium proteins that could predict clinical status of the donors. Several of these antibody responses were identified by multiple comparisons, including those against members of the serine enriched repeat antigen family and merozoite protein 4. Interestingly, both P. falciparum serine enriched repeat antigen-5 and merozoite protein 4 have been previously investigated for use in vaccines. This machine learning approach, never previously applied to proteome arrays, can be used to generate a list of potential seroprotective and/or diagnostic antigens candidates that can be further evaluated in longitudinal studies. Molecular & Cellular

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Section: S)mentioning

confidence: 85%

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Finney

Danziger

Molina

et al. 2014

Molecular & Cellular Proteomics

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“…However, some studies have reported on cross-reactivity of few antigens specific to pre-erythrocytic and erythrocytic asexual stages of multiple Plasmodium species. This includes: (i) recognition of P. falciparum asexual stage antigens by antibodies in sera from people exposed to P. vivax , (Kumar et al, 1992), and suppression of P. falciparum by sera from a case of P. vivax (Nagao et al, 2008), (ii) recognition of circumsporozoite protein (CSP) of P. falciparum and P. berghei by antibodies elicited by VMP001, a P. vivax CSP-based vaccine (VMP00) (Yadava et al, 2012), (iii) induction of cross-reactive and cross-protective antibodies by PfCelTOS, a highly conserved cell-traversal protein expressed on the surface of ookinetes and sporozoites (Bergmann-Leitner et al, 2010), and (iv) reported cross reactivity between apical membrane antigen 1, cytoadherence-linked asexual gene 9 product and merozoite surface protein 5 of P. falciparum and P. vivax (Costa et al, 2013; Igonet et al, 2007; Woodberry et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Antibodies elicited during natural infection in a predominantly Plasmodium falciparum transmission area cross-react with sexual stage-specific antigen in P. vivax

et al. 2017

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Infections caused by Plasmodium falciparum and P. vivax account for more than 90% of global malaria burden. Exposure to malaria parasite elicits immune responses during natural infection and it is generally believed that the immunity is not only stage specific but also species specific. However, partial genomic similarity for various antigens in different Plasmodium spp. raises the possibility of immunological cross-reactivity at the level of specific antigens. Serum samples collected from children who were permanent residents of a P. falciparum transmission area in Zimbabwe were screened for antibody reactivity against Pfs48/45, a P. falciparum gametocyte antigen and Pvs48/45, a P. vivax homolog of Pfs48/45 using ELISA. Western blotting was used to further confirm identity of the specific antibody reactivity to the Pfs48/45 and Pvs48/45 proteins. Pan Plasmodium PCR and nested PCR were used to confirm infection with the Plasmodium species. Twenty-seven percent (49/181) of the participants were found to be sero-positive for Pfs48/45 and 73% (n=36) of these Pfs48/45 positive sera also showed reactivity with Pvs48/45. Immune cross-reactivity revealed by ELISA was also confirmed by Western blot analysis using a panel of randomly selected 23 Pfs48/45 and Pvs48/45 ELISA positive samples. Nested PCR analysis of 27 blood samples randomly selected from the 36 that showed positive ELISA reactivity to both Pfs48/45 and Pvs48/45 antigens confirmed infection with P. falciparum and generalized absence of P. vivax except for a single sample which revealed PCR positivity for both P. vivax and P. falciparum. Our studies with sera samples from a predominantly P. falciparum transmission area in Zimbabwe suggest immunological cross-reactivity with Pvs48/45, thus raising the possibility of partial species cross-reactive immunity and possible cross-boosting of immunity during co-infection with P. falciparum and P. vivax.

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“…However, the presence of submicroscopic infections or the presence of residual antibodies from a previous infection(s) could not be ruled out by those authors. Similarly, there is a strong indication of the presence of cross-reactive responses to other sexual (17) and asexual (3,16,18) blood-stage antigens from the field. However, the data cannot be exclusively attributed to cross-reaction, as the presence of heterologous species, while rare, has not been ruled out.…”

Section: Resultsmentioning

confidence: 99%

“…Despite the presence of orthologous antigens, few studies have evaluated the presence of cross-reactive antibodies. Sera from regions with a predominance of one species, but not a total absence of the other species, have been shown to have cross-reactivity to some antigens, such as merozoite surface protein 1 (MSP-1) (15), MSP-5 (16), P. falciparum s48/45 (Pfs48/45) or P. vivax s48/45 (Pvs48/45) (17), and PfCLAG9 (18). Using P. falciparum and P. vivax protein microarrays, King and colleagues (3) observed cross-reactivity using sera from "essentially monoexposed" regions of endemicity.…”

mentioning

confidence: 99%

Mosquito Bite-Induced Controlled Human Malaria Infection with Plasmodium vivax or P. falciparum Generates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens

et al. 2019

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Seroepidemiological studies on the prevalence of antibodies to malaria antigens are primarily conducted on individuals from regions of endemicity. It is therefore difficult to accurately correlate the antibody responses to the timing and number of prior malaria infections. This study was undertaken to assess the evolution of antibodies to the dominant surface antigens of Plasmodium vivax and P. falciparum following controlled human malaria infection (CHMI) in malaria-naive individuals. Serum samples from malaria-naive adults, collected before and after CHMI with either P. vivax (n = 18) or P. falciparum (n = 18), were tested for the presence of antibodies to the circumsporozoite protein (CSP) and the 42-kDa fragment of merozoite surface protein 1 (MSP-142) of P. vivax and P. falciparum using an enzyme-linked immunosorbent assay (ELISA). Approximately 1 month following CHMI with either P. vivax or P. falciparum, >60% of subjects seroconverted to homologous CSP and MSP-1. More than 50% of the subjects demonstrated reactivity to heterologous CSP and MSP-142, and a similar proportion of subjects remained seropositive to homologous MSP-142 >5 months after CHMI. Computational analysis provides insight into the presence of cross-reactive responses. The presence of long-lived and heterologous reactivity and its functional significance, if any, need to be taken into account while evaluating malaria exposure in field settings.

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Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

Cited by 11 publications

References 47 publications

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Antibodies elicited during natural infection in a predominantly Plasmodium falciparum transmission area cross-react with sexual stage-specific antigen in P. vivax

Mosquito Bite-Induced Controlled Human Malaria Infection with Plasmodium vivax or P. falciparum Generates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens

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