Does Antibody Avidity to Plasmodium falciparum Merozoite Antigens Increase with Age in Individuals Living in Malaria-Endemic Areas?

Abstract

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.

Profiling the Quality and Quantity of Naturally Induced Antibody Responses Against Pfs230 and Pfs48/45 Among Non-Febrile Children Living in Southern Ghana: A Longitudinal Study

“…The relative IgG avidity against Pfs230 at a time point close to peak malaria season was observed to be significantly higher in older children (≥10 years) than in younger children (<10 years), suggesting that age could have an impact on the avidity. This increase in IgG antibody avidity with the increase in age could be due to increased exposure to the same antigen and hence the tendency of IgG avidity to develop or have matured better in adulthood than in childhood as recently reported ( Tassi Yunga et al., 2021 ). Lack of an association between the number of times a person had been infected with parasites during the follow-ups and antibody levels or avidities was not surprising as all microscopic infections determined contained only asexual parasites.…”

Atypical memory B cell frequency correlates with antibody breadth and function in malaria immune adults

“…This suggests intrinsic properties of an antigen could impact the avidity of the binding antibody. Previous studies in Ugandan children and adults living in high transmission areas found age-related effects on antibody avidity against some antigens (EBA-175 and MSP1-42) but not others (MSP2 and MSP3) 23 . Studies that have compared malaria antibody avidity between areas of differing transmission have largely focused on blood-stage antigens 22 , 23 .…”

“…Previous studies in Ugandan children and adults living in high transmission areas found age-related effects on antibody avidity against some antigens (EBA-175 and MSP1-42) but not others (MSP2 and MSP3) 23 . Studies that have compared malaria antibody avidity between areas of differing transmission have largely focused on blood-stage antigens 22 , 23 . It would be interesting to know if the avidity of antibodies against antigens of pre-erythrocytic and sexual stage show a similar pattern as blood stage antigens.…”