AUTHOR=Rogier Eric , Nace Doug , Dimbu Pedro R. , Wakeman Brian , Pohl Jan , Beeson James G. , Drakeley Chris , Tetteh Kevin , Plucinski Mateusz 

TITLE=Framework for Characterizing Longitudinal Antibody Response in Children After Plasmodium falciparum Infection

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.617951

DOI=10.3389/fimmu.2021.617951

ISSN=1664-3224

ABSTRACT=<p>Human <italic>Plasmodium</italic> infection produces a robust adaptive immune response. Time courses for 104 children followed for 42 days after initiation of <italic>Plasmodium falciparum</italic> chemotherapy were assayed for antibody levels to the five isotypes of human immunoglobulins (Ig) and 4 subclasses of IgG for 32 <italic>P. falciparum</italic> antigens encompassing all 4 parasite stages of human infection. IgD and IgE against these antigens were undetectable at 1:100 serum concentration, but other Ig isotypes and IgG subclasses were consistently observed against all antigens. Five quantitative parameters were developed to directly compare Ig response among isotypes and antigens: C<sub>max</sub>, maximum antibody level; Δ<sub>C</sub>, difference between C<sub>max</sub> and the antibody level at Day 0; t<sub>max</sub>, time in days to reach C<sub>max</sub>; t<sub>1/2</sub>, Ig signal half-life in days; t<sub>neg</sub>, estimated number of days until complete loss of Ig signal. Classical Ig patterns for a bloodborne pathogen were seen with IgM showing early t<sub>max</sub> and IgG production highest among Ig isotypes. However, some unexpected trends were observed such as IgA showing a biphasic pattern for many antigens. Variability among these dynamics of Ig acquisition and loss was noted for different <italic>P. falciparum</italic> antigens and able to be compared both quantitatively and statistically. This parametrization methodology allows direct comparison of Ig isotypes produced against various <italic>Plasmodium</italic> antigens following malaria infection, and the same methodology could be applied to other longitudinal serologic studies from <italic>P. falciparum</italic> or different pathogens. Specifically for <italic>P. falciparum</italic> seroepidemiological studies, reliable and quantitative estimates regarding the IgG dynamics in human populations can better optimize modeling efforts for serological outputs.</p>