scholarly journals Immunoglobulin G responses to variant forms of Plasmodium vivax merozoite surface protein 9 upon natural infection in Thailand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sunisa Songsaigath ◽  
Takashi Makiuchi ◽  
Chaturong Putaporntip ◽  
Urassaya Pattanawong ◽  
Napaporn Kuamsab ◽  
...  

AbstractMerozoite surface protein 9 (MSP9) constitutes a ligand complex involved in erythrocyte invasion by malarial merozoites and is a promising vaccine target. Plasmodium vivax MSP9 (PvMSP9) is immunogenic upon natural malaria exposure. To address whether sequence diversity in PvMSP9 among field isolates could affect natural antibody responses, the recombinant proteins representing two variants each for the N- and the C-terminal domains of PvMSP-9 were used as antigens to assess antibody reactivity among 246 P. vivax-infected patients’ sera from Tak and Ubon Ratchathani Provinces in Thailand. Results revealed that the seropositivity rates of IgG antibodies to the N-terminal antigens were higher than those to the C-terminal antigens (87.80% vs. 67.48%). Most seropositive sera were reactive to both variants, suggesting the presence of common epitopes. Variant-specific antibodies to the N- and the C-terminal antigens were detected in 15.85% and 16.70% of serum samples, respectively. These seropositivity rates were not significant difference between provinces. The seropositivity rates, levels and avidity of anti-PvMSP9 antibodies exhibited positive trends towards increasing malaria episodes. The IgG isotype responses to the N- and the C-terminal antigens were mainly IgG1 and IgG3. The profile of IgG responses may have implications for development of PvMSP9-based vaccine.

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 282
Author(s):  
Elizabeth Villasis ◽  
Katherine Garro ◽  
Angel Rosas-Aguirre ◽  
Pamela Rodriguez ◽  
Jason Rosado ◽  
...  

The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72–0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67–0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74–0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon.


2005 ◽  
Vol 73 (9) ◽  
pp. 5936-5944 ◽  
Author(s):  
Sheetij Dutta ◽  
Deep C. Kaushal ◽  
Lisa A. Ware ◽  
Sunil K. Puri ◽  
Nuzhat A. Kaushal ◽  
...  

ABSTRACT The 42-kDa fragment of the merozoite surface protein 1 (MSP-142) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of Plasmodium vivax MSP-142 (PvMSP-142) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun. 69:5464-5470, 2001). We report here a process to manufacture the same PvMSP-142 protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-142 protein by using a heterologous but closely related P. cynomolgi-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the P. cynomolgi MSP-142 (PcMSP-142) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-142-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (P < 0.05). Except the soluble PcMSP-142 group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm−3. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-142 and PvMSP-142 proteins also appeared to have a similar partially protective effect.


2015 ◽  
Vol 23 (2) ◽  
pp. 104-116 ◽  
Author(s):  
Arlene E. Dent ◽  
Indu Malhotra ◽  
Xuelie Wang ◽  
Denise Babineau ◽  
Kee Thai Yeo ◽  
...  

ABSTRACTIgG antibodies toPlasmodium falciparumare transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized toP. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitizedin utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk ofP. falciparuminfection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.


2002 ◽  
Vol 99 (25) ◽  
pp. 16348-16353 ◽  
Author(s):  
C. Putaporntip ◽  
S. Jongwutiwes ◽  
N. Sakihama ◽  
M. U. Ferreira ◽  
W.-G. Kho ◽  
...  

2004 ◽  
Vol 4 (4) ◽  
pp. 309-319 ◽  
Author(s):  
Julian C. Rayner ◽  
Curtis S. Huber ◽  
Dmitry Feldman ◽  
Paul Ingravallo ◽  
Mary R. Galinski ◽  
...  

2005 ◽  
Vol 73 (6) ◽  
pp. 3462-3470 ◽  
Author(s):  
Indu Malhotra ◽  
Peter Mungai ◽  
Eric Muchiri ◽  
John Ouma ◽  
Shobhona Sharma ◽  
...  

ABSTRACT Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jenni Hietanen ◽  
Anongruk Chim-ong ◽  
Jetsumon Sattabongkot ◽  
Wang Nguitragool

Abstract Background Plasmodium vivax is the most prevalent malaria parasite in many countries. A better understanding of human immunity to this parasite can provide new insights for vaccine development. Plasmodium vivax Reticulocyte Binding Proteins (RBPs) are key parasite proteins that interact with human proteins during erythrocyte invasion and are targets of the human immune response. The aim of this study is to characterize the human antibody response to RBP2P1, the most recently described member of the RBP family. Methods The levels of total IgG and IgM against RBP2P1 were measured using plasmas from 68 P. vivax malaria patients and 525 villagers in a malarious village of western Thailand. The latter group comprises asymptomatic carriers and healthy uninfected individuals. Subsets of plasma samples were evaluated for anti-RBP2P1 IgG subtypes and complement-fixing activity. Results As age increased, it was found that the level of anti-RBP2P1 IgG increased while the level of IgM decreased. The main anti-RBP2P1 IgG subtypes were IgG1 and IgG3. The IgG3-seropositive rate was higher in asymptomatic carriers than in patients. The higher level of IgG3 was correlated with higher in vitro RBP2P1-mediated complement fixing activity. Conclusions In natural infection, the primary IgG response to RBP2P1 was IgG1 and IgG3. The predominance of these cytophilic subtypes and the elevated level of IgG3 correlating with complement fixing activity, suggest a possible role of anti-RBP2P1 antibodies in immunity against P. vivax.


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