scholarly journals Does Antibody Avidity to Plasmodium falciparum Merozoite Antigens increase with Age in Individuals living in Malaria-Endemic Areas?

2021 ◽  
Author(s):  
Samuel Tassi Yunga ◽  
Naveen Bobbili ◽  
Yukie M. Lloyd ◽  
Jovikka Antallan ◽  
Masako Matsunaga ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Affinity Maturation ◽  
High Avidity ◽  
Plasma Samples ◽  
Avidity Index ◽  
Hyperendemic Area ◽  
Age Related ◽  
Falciparum Merozoite ◽  
Merozoite Antigens ◽  
Strength Of Association

Introduction: High avidity antibodies (Abs) are acquired after a few Plasmodium falciparum infections in low transmission areas, but it remains unclear if Ab avidity to different merozoite antigens increases with age in individuals with persistent antigenemia and if so, when a fully mature Ab response occurs. Methods: The study used plasma samples collected between 1996 and 1998 from 566 individuals aged 4-84 years in Simbok, Cameroon where residents received an estimated 1.6 infectious mosquito bites/person/night. Plasma samples were examined for Ab levels (median fluorescence intensity, MFI) and Ab avidity index (AI = [MFI after treatment with 2M NH4SCN/MFI without salt] x 100) using a bead-based multiplex immunoassay for recombinant AMA1, EBA-175, MSP1-42 (3D7, FVO), MSP2 (3D7, Fc27), and MSP3. Results: Blood-smear positivity for P. falciparum declined with age from 54.3% at 4-5 years to 18% at 16-40 years and <11% at >40 years of age, although most individuals had submicroscopic parasitemia. Ab affinity maturation, based on age-related patterns of median AI, percent of individuals with AI ≥50 and strength of association between MFI and AI, occurred at different rates among the antigens: developing rapidly before age 4 years for AMA1, increasing gradually with age for EBA-175 and MSP1 until ∼16-25 years, but occurring negligibly for MSP2 and MSP3. Conclusion: In a hyperendemic area with perennial transmission, affinity maturation resulting in an increase in the proportion of high avidity Abs occurred for some merozoite antigens, in parallel with a decline in malaria slide passivity, but not for others.

scholarly journals Measuring antibody avidity to Plasmodium falciparum merozoite antigens using a multiplex immunoassay approach

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Diane Wallace Taylor ◽  
Naveen Bobbili ◽  
Alex Kayatani ◽  
Samuel Tassi Yunga ◽  
Winifrida Kidima ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antibody Avidity ◽  
Multiplex Immunoassay ◽  
Falciparum Merozoite ◽  
Merozoite Antigens

scholarly journals Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity

2021 ◽  
Vol 11 ◽  
Author(s):  
Isaac Ssewanyana ◽  
John Rek ◽  
Isabel Rodriguez ◽  
Lindsey Wu ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Affinity Maturation ◽  
Igg Subclasses ◽  
Rapid Decline ◽  
Avidity Index ◽  
Time Points ◽  
Rate Of Decay ◽  
Differential Expansion ◽  
Strength Of Association ◽  
Multiplex Bead

Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response. Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at two time points during high malaria transmission and two time points following a dramatic reduction in transmission. Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age. Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

scholarly journals Immunoglobulin G Subclass-Specific Responses against Plasmodium falciparum Merozoite Antigens Are Associated with Control of Parasitemia and Protection from Symptomatic Illness

2009 ◽  
Vol 77 (3) ◽  
pp. 1165-1174 ◽  
Author(s):  
Danielle I. Stanisic ◽  
Jack S. Richards ◽  
Fiona J. McCallum ◽  
Pascal Michon ◽  
Christopher L. King ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunoglobulin G ◽  
Vaccine Development ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Igg Subclass ◽  
Apical Membrane Antigen 1 ◽  
Falciparum Merozoite ◽  
Merozoite Antigens

ABSTRACT Substantial evidence indicates that antibodies to Plasmodium falciparum merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one subclass. The profiles of IgG subclasses differed somewhat for different alleles of MSP2 but not for different variants of AMA-1. Individuals did not appear to have a propensity to make a specific subclass response irrespective of the antigen. Instead, data suggest that subclass responses to each antigen are generated independently among individuals and that antigen properties, rather than host factors, are the major determinants of IgG subclass responses. High levels of AMA-1-specific IgG3 and MSP1-19-specific IgG1 were strongly predictive of a reduced risk of symptomatic malaria and high-density P. falciparum infections. However, no antibody response was significantly associated with protection from parasitization per se. Our findings have major implications for understanding human immunity and for malaria vaccine development and evaluation.

scholarly journals Analysis of Antibodies to Newly Described Plasmodium falciparum Merozoite Antigens Supports MSPDBL2 as a Predicted Target of Naturally Acquired Immunity

2013 ◽  
Vol 81 (10) ◽  
pp. 3835-3842 ◽  
Author(s):  
Kevin K. A. Tetteh ◽  
Faith H. A. Osier ◽  
Ali Salanti ◽  
Gathoni Kamuyu ◽  
Laura Drought ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Risk Ratio ◽  
Statistical Significance ◽  
Clinical Malaria ◽  
Content Type ◽  
Type Antigen ◽  
Falciparum Merozoite ◽  
Merozoite Antigens ◽  
Allelic Type

ABSTRACTProspective studies continue to identify malaria parasite genes with particular patterns of polymorphism which indicate they may be under immune selection, and the encoded proteins require investigation. Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed inPlasmodium falciparumschizonts and merozoites: MSPDBL1 (also termed MSP3.4) and MSPDBL2 (MSP3.8), which possess Duffy binding-like (DBL) domains, and SURFIN4.2, encoded by a member of the surface-associated interspersed (surf) multigene family. After testing the antigenicities of these reagents by murine immunization and parasite immunofluorescence, we analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [n= 497] and Ngerenya [n= 461]). As expected, the prevalence and levels of serum antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-up surveillance. Antibodies to the polymorphic central region of MSPDBL2 were associated with reduced risk of malaria in both cohorts, with statistical significance remaining for the 3D7 allelic type after adjustment for individuals' ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95% confidence interval [CI], 0.28 to 0.93; Ngerenya, risk ratio, 0.38, and 95% CI, 0.18 to 0.82). For the MSPDBL1 Palo Alto allelic-type antigen, there was a protective association in one cohort (Ngerenya, risk ratio, 0.53, and 95% CI, 0.32 to 0.89), whereas the other antigens showed no protective associations after adjustment. These findings support the prediction that antibodies to the polymorphic region of MSPDBL2 contribute to protective immunity.

scholarly journals Measuring Antibody Avidity To Plasmodium Falciparum Merozoite Antigens Using A Multiplex Immunoassay Approach

2020 ◽  
Author(s):  
Diane Wallace Taylor ◽  
Naveen Bobbili ◽  
Alexander K Kayatani ◽  
Samuel Tassi-Yunga ◽  
Rose FG Leke
Keyword(s):  
Plasmodium Falciparum ◽  
Clonal Selection ◽  
Ammonium Thiocyanate ◽  
Plasmodium Falciparum Malaria ◽  
Affinity Maturation ◽  
Binding Studies ◽  
Simple Method ◽  
Antibody Avidity ◽  
Merozoite Antigens ◽  
One Year

Abstract Background: Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not take place to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that used a single chaotropic concentration. Methods: The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH4SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to i) identify the assay with the widest range of AI (discriminatory power), ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and iii) evaluate assay repeatability. Results: Overall, 4M GdHCl and 8M urea were weaker chaotropes than 3M NH4SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH4SCN. Titration of NH4SCN revealed that 2M urea gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 one-year old infants in Cameroon showed that 2.1M ± 0.32 (mean ± SD) NH4SCN (adults) and 1.8M ± 0.23M released 50% of bound Ab from the merozoite antigens. The final avidity multiplex assay was highly repeatable. Conclusions. An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2M) of NH4SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.

scholarly journals Age-Related Differences in Naturally Acquired T Cell Memory to Plasmodium falciparum Merozoite Surface Protein 1

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24852 ◽  
Author(s):  
Kiprotich Chelimo ◽  
Paula B. Embury ◽  
Peter Odada Sumba ◽  
John Vulule ◽  
Ayub V. Ofulla ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
T Cell Memory ◽  
Cell Memory ◽  
Merozoite Surface Protein 1 ◽  
Age Related ◽  
Falciparum Merozoite

scholarly journals Measuring Antibody Avidity to Plasmodium Falciparum Merozoite Antigens Using a Multiplex Immunoassay Approach

2020 ◽  
Author(s):  
Diane Wallace Taylor ◽  
Naveen Bobbili ◽  
Alexander K Kayatani ◽  
Samuel Tassi-Yunga ◽  
Winifrida Kidima ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clonal Selection ◽  
Ammonium Thiocyanate ◽  
Affinity Maturation ◽  
Binding Studies ◽  
Simple Method ◽  
Antibody Avidity ◽  
Merozoite Antigens ◽  
Adult Plasma ◽  
One Year

Abstract Background: Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not occur to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that uses a single chaotropic concentration.Methods: The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH4SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to i) identify the assay with the widest range of AI (discriminatory power), ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and iii) evaluate assay repeatability. Results: Overall, 4M GdHCl and 8M urea were weaker chaotropes than 3M NH4SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH4SCN. Titration of NH4SCN revealed that 2M NH4SCN gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 one-year old infants in Cameroon showed that 2.1M ± 0.32 (mean ± SD) NH4SCN (adults) and 1.8M ± 0.23M (infants) released 50% of bound Ab from the merozoite antigens. Conclusions. An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2M) of NH4SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.

scholarly journals Cytophilic Immunoglobulin Responses to Plasmodium falciparum Glutamate-Rich Protein Are Correlated with Protection against Clinical Malaria in Dielmo, Senegal

2000 ◽  
Vol 68 (5) ◽  
pp. 2617-2620 ◽  
Author(s):  
Claude Oeuvray ◽  
Michael Theisen ◽  
Christophe Rogier ◽  
Jean-Francois Trape ◽  
Søren Jepsen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Immunity ◽  
Clinical Malaria ◽  
Parasite Growth ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Confounding Effect ◽  
Human Antibodies ◽  
Age Related ◽  
Effect Of Age

ABSTRACT The goal of this study was to analyze antibody responses toPlasmodium falciparum glutamate-rich protein (GLURP) using clinical data and plasma samples obtained from villagers of Dielmo, Senegal. This molecule was chosen because it is targeted by human antibodies which induce parasite growth inhibition in antibody-dependent cellular inhibition (ADCI) assays. The results showed a strong correlation between protection against malaria attacks and levels of immunoglobulin G2 (IgG2) and IgG3 against GLURP94–489 (R0) and IgG3 against GLURP705–1178 (R2) when corrected for the confounding effect of age-related exposure to malaria. Thus, GLURP may play a role in the induction of protective immunity against P. falciparum malaria.

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