Abstract
Human Plasmodium infection produces a robust adaptive immune response. Time courses for 104 children followed for 42 days after initiation of Plasmodium falciparum chemotherapy were assayed for antibody levels to the five isotypes of human immunoglobulins (Ig) and 4 subclasses of IgG for 32 P. falciparum 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: Cmax, maximum antibody level; ΔC, difference between Cmax and the antibody level at Day 0; tmax, time in days to reach Cmax; t1/2, Ig signal half-life in days; tneg, estimated number of days until complete loss of Ig signal. Classical Ig patterns for a bloodborne pathogen were seen with IgM showing early tmax 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 P. falciparum antigens and able to be compared both quantitatively and statistically. This parametrization methodology allows direct comparison of Ig isotypes produced against various Plasmodium antigens following malaria infection, and the same methodology could be applied to other longitudinal serologic studies from P. falciparum or different pathogens. Specifically for P. falciparum seroepidemiological studies, reliable and quantitative estimates regarding the IgG dynamics in human populations can better optimize modeling efforts for serological outputs.
Highlights
The vertebrate hosts of malaria have been required to endure malaria infection for tens of millions of years, and fossil evidence for Plasmodium and their predecessors far precedes the rise of the genus Homo [1, 2]
The introduction of standardized antimalarial medications and therapeutics has only occurred very recently in human history [3], and intense evolutionary pressure has been placed on the human genome to alter traits of red blood cells as well as ensure a vigorous, yet measured, immune response against the parasite is elicited [4]
Classswitched populations of both effector and memory B cells develop after malaria exposure in humans, and more recently, memory B cells activated by Plasmodium antigens have been further subdivided into “classical” and “atypical” [27, 28]
Summary
The vertebrate hosts of malaria have been required to endure malaria infection for tens of millions of years, and fossil evidence for Plasmodium and their predecessors far precedes the rise of the genus Homo [1, 2]. The pre-dominance of antigens in laboratory use today are produced during blood stage Plasmodium infection and would be expected to be at abundant levels in the host blood during the merozoite multiplication cycles Outside of these erythrocyte-stage antigens, antigens eliciting antibody and other adaptive responses have been identified for the other human Plasmodium falciparum infection stages: sporozoite [23, 24], liver (hepatocyte) [25], and sexual (gametocyte) [26]. Classswitched populations of both effector and memory B cells develop after malaria exposure in humans, and more recently, memory B cells activated by Plasmodium antigens have been further subdivided into “classical” and “atypical” [27, 28]. Contrasting the defined parameters for a study population among Ig isotypes and among antigens can assist in elucidating the true differences in humoral responses to infection or vaccination
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