scholarly journals Quantification of the Dynamics of Antibody Response to Malaria to Inform Sero-Surveillance in Pregnant Women

2021 ◽  
Author(s):  
A.D.V.Tharkeshi T. Dharmaratne ◽  
Saber Dini ◽  
Katherine O’Flaherty ◽  
David J Price ◽  
Rose McGready ◽  
...  
Keyword(s):  
Antibody Response ◽  
Pregnant Women ◽  
Malaria Transmission ◽  
Linear Mixed Model ◽  
Apical Membrane ◽  
Chondroitin Sulphate ◽  
Antibody Responses ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Low Malaria Transmission

Abstract Background: Malaria remains a major public health threat and in low malaria transmission areas new tools are needed to detect infections for prompt treatment and to progress elimination efforts. Pregnant women are particularly vulnerable to malaria infections and access routine antenatal care, presenting a unique sentinel population to apply novel sero-surveillance tools to measure malaria transmission. The aim of this study was to quantify the dynamic antibody responses to multiple antigens during pregnancy to identify a single or multiple antibody response of exposure to malaria in pregnancy. Methods: Antibody-mediated immunity responses to six parasite antigens (five commonly studied merozoite antigens and the variant surface antigen 2-chondroitin sulphate A (VAR2CSA), a pregnancy-specific erythrocytic antigen) were measured over the gestation period until delivery (median of 7 measurements/woman) in 250 pregnant women who attended antenatal clinics located at the Thai-Myanmar border. A multivariate mixture linear mixed model was used to cluster the pregnant women into groups that have similar longitudinal antibody responses to all six antigens over the gestational period using a Bayesian approach. The variable-specific entropy was calculated to identify the antibody responses that have the highest influence on the classification of the women into clusters, and subsequent agreement with grouping of women based on exposure to malaria during pregnancy. Results: Of the 250 pregnant women, 135 had a Plasmodium infection detected by light microscopy during pregnancy, defined as cases. The antibody responses to all six antigens accurately identified the women who did not have a malaria infection detected during pregnancy (93%, 107/115 controls). Antibody responses to P. falciparum merozoite surface protein 3 (PfMSP3) and P. vivax apical membrane antigen 1 (PvAMA1) were the least dynamic. Antibody responses to the antigens P. falciparum apical membrane antigen 1 (PfAMA1) and PfVAR2CSA were able to identify the majority of the cases more accurately (63%, 85/135). Conclusion: These findings suggest that the combination of antibodies, PfAMA1 and PfVAR2CSA, may be useful for sero-surveillance of malaria infections in pregnant women, particularly in low malaria transmission settings, leading to the early detection and treatment of malaria infections in pregnant women.

scholarly journals Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses

2008 ◽  
Vol 16 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Michelle M. Lynch ◽  
Amy Cernetich-Ott ◽  
William P. Weidanz ◽  
James M. Burns
Keyword(s):  
Apical Membrane ◽  
Protective Efficacy ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasmodium Chabaudi ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Surface Protein 1 ◽  
Apical Membrane Antigen

ABSTRACT For the development of blood-stage malaria vaccines, there is a clear need to establish in vitro measures of the antibody-mediated and the cell-mediated immune responses that correlate with protection. In this study, we focused on establishing correlates of antibody-mediated immunity induced by immunization with apical membrane antigen 1 (AMA1) and merozoite surface protein 142 (MSP142) subunit vaccines. To do so, we exploited the Plasmodium chabaudi rodent model, with which we can immunize animals with both protective and nonprotective vaccine formulations and allow the parasitemia in the challenged animals to peak. Vaccine formulations were varied with regard to the antigen dose, the antigen conformation, and the adjuvant used. Prechallenge antibody responses were evaluated by enzyme-linked immunosorbent assay and were tested for a correlation with protection against nonlethal P. chabaudi malaria, as measured by a reduction in the peak level of parasitemia. The analysis showed that neither the isotype profile nor the avidity of vaccine-induced antibodies correlated with protective efficacy. However, high titers of antibodies directed against conformation-independent epitopes were associated with poor vaccine performance and may limit the effectiveness of protective antibodies that recognize conformation-dependent epitopes. We were able to predict the efficacies of the P. chabaudi AMA1 (PcAMA1) and P. chabaudi MSP142 (PcMSP142) vaccines only when the prechallenge antibody titers to both refolded and reduced/alkylated antigens were considered in combination. The relative importance of these two measures of vaccine-induced responses as predictors of protection differed somewhat for the PcAMA1 and the PcMSP142 vaccines, a finding confirmed in our final immunization and challenge study. A similar approach to the evaluation of vaccine-induced antibody responses may be useful during clinical trials of Plasmodium falciparum AMA1 and MSP142 vaccines.

Antibody response of naturally infected individuals to recombinant Plasmodium vivax apical membrane antigen-1

2005 ◽  
Vol 35 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Maria Helena C. Rodrigues ◽  
Karina M. Rodrigues ◽  
Tatiane R. Oliveira ◽  
Andréia N. Cômodo ◽  
Mauricio M. Rodrigues ◽  
...  
Keyword(s):  
Antibody Response ◽  
Plasmodium Vivax ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

scholarly journals Allele Specificity of Naturally Acquired Antibody Responses against Plasmodium falciparum Apical Membrane Antigen 1

2005 ◽  
Vol 73 (1) ◽  
pp. 422-430 ◽  
Author(s):  
Alfred Cortés ◽  
Mata Mellombo ◽  
Rosella Masciantonio ◽  
Vince J. Murphy ◽  
John C. Reeder ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Apical Membrane ◽  
Age Groups ◽  
Antibody Responses ◽  
Allelic Form ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Younger Age ◽  
Merozoite Antigens ◽  
Allele Specificity

ABSTRACT Antibody responses against proteins located on the surface or in the apical organelles of merozoites are presumed to be important components of naturally acquired protective immune responses against the malaria parasite Plasmodium falciparum. However, many merozoite antigens are highly polymorphic, and antibodies induced against one particular allelic form might not be effective in controlling growth of parasites expressing alternative forms. The apical membrane antigen 1 (AMA1) is a polymorphic merozoite protein that is a target of naturally acquired invasion-inhibitory antibodies and is a leading asexual-stage vaccine candidate. We characterized the antibody responses against AMA1 in 262 individuals from Papua New Guinea exposed to malaria by using different allelic forms of the full AMA1 ectodomain and some individual subdomains. The majority of individuals had very high levels of antibodies against AMA1. The prevalence and titer of these antibodies increased with age. Although antibodies against conserved regions of the molecule were predominant in the majority of individuals, most plasma samples also contained antibodies directed against polymorphic regions of the antigen. In a few individuals, predominantly from younger age groups, the majority of antibodies against AMA1 were directed against polymorphic epitopes. The D10 allelic form of AMA1 apparently contains most if not all of the epitopes present in the other allelic forms tested, which might argue for its inclusion in future AMA1-based vaccines to be tested. Some important epitopes in AMA1 involved residues located in domain II or III but depended on more than one domain.

Babesia gibsoni: An apical membrane antigen-1 homologue and its antibody response in the infected dogs

2006 ◽  
Vol 114 (4) ◽  
pp. 329-333 ◽  
Author(s):  
Jinlin Zhou ◽  
Jun Yang ◽  
Guohong Zhang ◽  
Yoshifumi Nishikawa ◽  
Kozo Fujisaki ◽  
...  
Keyword(s):  
Antibody Response ◽  
Apical Membrane ◽  
Babesia Gibsoni ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

scholarly journals Use of Immunodampening To Overcome Diversity in the Malarial Vaccine Candidate Apical Membrane Antigen 1

2014 ◽  
Vol 82 (11) ◽  
pp. 4707-4717 ◽  
Author(s):  
Karen S. Harris ◽  
Christopher G. Adda ◽  
Madhavi Khore ◽  
Damien R. Drew ◽  
Antonina Valentini-Gatt ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antibody Response ◽  
Vaccine Candidate ◽  
Apical Membrane ◽  
Targeted Mutagenesis ◽  
Parasite Line ◽  
Content Type ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Mutation Strategy

ABSTRACTApical membrane antigen 1 (AMA1) is a leading malarial vaccine candidate; however, its polymorphic nature may limit its success in the field. This study aimed to circumvent AMA1 diversity by dampening the antibody response to the highly polymorphic loop Id, previously identified as a major target of strain-specific, invasion-inhibitory antibodies. To achieve this, five polymorphic residues within this loop were mutated to alanine, glycine, or serine in AMA1 of the 3D7 and FVOPlasmodium falciparumstrains. Initially, the corresponding antigens were displayed on the surface of bacteriophage, where the alanine and serine but not glycine mutants folded correctly. The alanine and serine AMA1 mutants were expressed inEscherichia coli, refoldedin vitro, and used to immunize rabbits. Serological analyses indicated that immunization with a single mutated form of 3D7 AMA1 was sufficient to increase the cross-reactive antibody response. Targeting the corresponding residues in an FVO backbone did not achieve this outcome. The inclusion of at least one engineered form of AMA1 in a biallelic formulation resulted in an antibody response with broader reactivity against different AMA1 alleles than combining the wild-type forms of 3D7 and FVO AMA1 alleles. For one combination, this extended to an enhanced relative growth inhibition of a heterologous parasite line, although this was at the cost of reduced overall inhibitory activity. These results suggest that targeted mutagenesis of AMA1 is a promising strategy for overcoming antigenic diversity in AMA1 and reducing the number of variants required to induce an antibody response that protects against a broad range ofPlasmodium falciparumAMA1 genotypes. However, optimization of the immunization regime and mutation strategy will be required for this potential to be realized.

scholarly journals Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Toussaint Rouamba ◽  
Sékou Samadoulougou ◽  
Mady Ouédraogo ◽  
Hervé Hien ◽  
Halidou Tinto ◽  
...  
Keyword(s):  
Burkina Faso ◽  
Pregnant Women ◽  
Malaria Transmission ◽  
Asymptomatic Malaria ◽  
Cross Sectional ◽  
Transmission Season ◽  
Low Transmission ◽  
High Transmission ◽  
Asymptomatic Carriage ◽  
Low Malaria Transmission

Abstract Background Malaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level. Methods Data of 1751 pregnant women from October 2013 to March 2014 and 1931 pregnant women from April 2017 to June 2017 were drawn from two cross-sectional household surveys conducted in 24 health districts of Burkina Faso. Pregnant women were tested for malaria in their household after consenting. Asymptomatic carriage was defined as a positive result from malaria rapid diagnostic tests in the absence of clinical symptoms of malaria. Anaemia was defined as haemoglobin level less than 11 g/dL in the first and third trimester and less than 10.5 g/dL in the second trimester of pregnancy. Results Prevalence of asymptomatic malaria in pregnancy was estimated at 23.9% (95% CI 20.2–28.0) during the high transmission season (October–November) in 2013. During the low transmission season, it was 12.7% (95% CI 10.9–14.7) between December and March in 2013–2014 and halved (6.4%; 95% CI 5.3–7.6) between April and June 2017. Anaemia prevalence was estimated at 59.4% (95% CI 54.8–63.8) during the high transmission season in 2013. During the low transmission season, it was 50.6% (95% CI 47.7–53.4) between December and March 2013–2014 and 65.0% (95% CI 62.8–67.2) between April and June, 2017. Conclusion This study revealed that the prevalence of malaria asymptomatic carriage and anaemia among pregnant women at the community level remain high throughout the year. Thus, more efforts are needed to increase prevention measures such as IPTp–SP coverage in order to reduce anaemia and contribute to preventing low birth weight and poor pregnancy outcomes.

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