Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon

Abstract

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms.

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

“…Thus, no obvious target epitope was identified to define the phenotype of either population. These results were similar to those recently reported by Fratus et al [18], which found no diagnostic serological differences between asymptomatic and symptomatic Pf malaria patients in the Brazilian Amazon, which like Haiti, is an area of low disease transmission. Several proteins previously explored in studies that have been conducted in Africa [22, 46, 47] that demonstrate protection in those individuals to well documented Pf antigens as well as potential humoral vaccine targets were observed in the top twenty antigens based on magnitude in both of our patient cohorts (Tables 1 & 2).…”

“…Immunological studies (cellular immune responses, chemokine/cytokine differences and various humoral responses) performed in other malaria endemic regions have been documented [10–16]. For asymptomatic infections [17, 18], the focus of most of these investigations has been on a single chemokine/cytokine or a particular cellular population percentage noted when comparing individuals with either asymptomatic vs. symptomatic malaria. Furthermore, only a few comprehensive investigations into the adaptive immunologic recall response to Plasmodium infection have been performed and nowhere has the humoral, cellular and chemokine/cytokine responses all been observed in one encompassing study.…”

Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area

“…In fact, studies have reported a high frequency of asymptomatic malaria infections among individuals in this area. 25,26,[37][38][39][40] In this regard, the population in the present study has been living in the Amazon region for an average of 24 years. Most likely, given the high prevalence of P. vivax in relation to P. falciparum in the area, the number of malaria infections does not necessarily mean stimulation of responses to P. falciparum antigens.…”

Immunoproteomics of Plasmodium falciparum-infected red blood cell membrane fractions

“…Recombinant expression of merozoite antigens and ultimately recognition of recombinant antigens by symptomatic and asymptomatic plasma antibodies showed that merozoite antigen recognition occurred regardless of symptoms and that other factors may contribute to clinical protection acquisition ( Medeiros et al 2013 ). Another study correlating the symptomatic/asymptomatic status with infected red blood cell (iRBC) recognition found no striking difference in the frequency and intensity of antibody recognition ( Fratus et al 2014 ). In contrast, several studies showed that plasmodial proteins displayed on iRBCs are responsible for: (i) targeted antigen recognition and associated immunity and (ii) immune system escape by antigenic variation ( Leech et al 1984 , Cheng et al 1998 , Winter et al 2005 , Chan et al 2012 ).…”