Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria

Abstract

BackgroundPlasmodium falciparum EBA175 and PfRh2 belong to two main families involved in parasite invasion, and both are potential vaccine candidates. Current knowledge is limited regarding which target antigens and subclasses of antibodies are actually important for protection, and how naturally acquired immunity is achieved.MethodsRepeated blood samples were collected from individuals in Nigeria over a period of almost one year. ELISA was used to analyse subclasses of IgG responses.ResultsFor both EBA175 (region III-V) and (a fragment of) PfRh2, the dominant antibody responses consisted of IgG1 and IgG3 followed by IgG2, while for PfRh2 there was also a relatively prominent response for IgG4. High levels of IgG1, IgG2 and IgG3 for EBA175 and total IgG for PfRh2 correlated significantly with a lower parasitaemia during the study period. Children with HbAS had higher levels of some subclasses compared to children with HbAA, while in adults the pattern was the opposite. The half-lives of IgG2 and IgG4 against EBA175 were clearly shorter than those for IgG1 and IgG3.ConclusionEBA175 and PfRh2 are potential targets for protective antibodies since both correlated with lower parasitaemia. The shorter half-lives for IgG2 and IgG4 might explain why these subclasses are often considered less important in protection against malaria. Triggering the right subclass responses could be of critical importance in a successful vaccine. Further studies are needed to evaluate the role of haemoglobin polymorphisms and their malaria protective effects in this process.

Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development

“…IgG subclass responses to some P. vivax antigens such as RBP1a, DBPII, MSP1 19, and CSP ( França et al, 2016b ; Tran et al, 2005 ; Maestre et al, 2010 ; Yildiz Zeyrek et al, 2011 ; Zeyrek et al, 2008 ), as well as several different P. falciparum antigens ( Stanisic et al, 2015 ; Ahmed Ismail et al, 2014 ; Richards et al, 2010 ; Reiling et al, 2010 ; Noland et al, 2015 ; Tongren et al, 2006 ) have consistently shown that the presence of IgG1 and/or IgG3 in variable ratios is likely to play a role in protection against infection and/or clinical disease. The role of IgG2 and IgG4 antibodies however, remains mostly unclear.…”

Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children

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Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry-Associated Membrane Antigen

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