Abstract
Within-host competition among parasite genotypes affects epidemiology as well as the evolution of virulence. In the rodent malaria Plasmodium chabaudi, competition among genotypes, as well as clone-specific and clone-transcending immunity are well documented. However, variation among genotypes in the induction of antibodies is not well understood, despite the important role of antibodies in the clearance of malaria infection. Here, we quantify the potential for antibodies induced by one clone to bind another (i.e., to cause antibody-mediated apparent competition) for nine genetically distinct P. chabaudi clones. We hypothesised that clones would vary in the strength of antibody induction, and that the propensity for clone-transcending immunity between a pair of clones would increase with increasing genetic relatedness at key antigenic loci. Using serum collected from mice 35days post-infection, we measured titres of antibody to an unrelated antigen, Keyhole Limpet Haemocyanin (KLH), and two malaria antigens: recombinant Apical Membrane Antigen-1 (AMA-1) and Merozoite Surface Protein-119 (MSP-119). Amino acid sequence homology within each antigenic locus was used as a measure of relatedness. We found significant parasite genetic variation for the strength of antibody induction. We also found that relatedness at MSP-119 but not AMA-1 predicted clone-transcending binding. Our results help explain the outcome of chronic-phase mixed infections and generate testable predictions about the pairwise competitive ability of P. chabaudi clones.
Highlights
Intraspecific competition among parasites in mixed-genotype infections is expected to affect the evolution of parasite traits and of virulence (Mideo, 2009)
Three proteins were used in this study: Keyhole Limpet Haemocyanin, or KLH (SIGMA) and two recombinant malaria antigens; Merozoite Surface Protein-119 (MSP-119) and Apical Membrane Antigen-1 (AMA-1)
Whilst natural Plasmodium infections may comprise many genotypes, it is common for two genotypes per host to be observed (e.g., (Anderson et al, 2000; Auburn et al, 2012; Manske et al, 2012; Vardo and Schall, 2007)); investigating the potential for immune-mediated interactions to occur between pairs of clones represents a tractable first step to studying more complex the greater number of polymorphisms in AMA-1, only some of which are relevant to binding of host antibodies and/or differential immunogenicity of AMA-1 variants (as described in Plasmodium falciparum; (Drew et al, 2012; Kusi et al, 2009))
Summary
Intraspecific competition among parasites in mixed-genotype infections is expected to affect the evolution of parasite traits and of virulence (degree of harm done to hosts) (Mideo, 2009). To study the induction of clone-transcending antibody, we measured binding of antibodies to two recombinant malaria antigens, Apical Membrane Antigen-1 (AMA-1) and Merozoite Surface Protein-119 (MSP-119) These antigens are both malaria vaccine candidates (Anders et al, 1998; Burns et al, 2004; Crewther et al, 1996; Dodoo et al, 2008; Hensmann et al, 2004) that are known to be polymorphic in P. chabaudi (Cheesman et al, 2009; Crewther et al, 1996; McKean et al, 1993). Under terminal anaesthesia, in the early chronic phase of infection (day 35 post-infection) This timepoint was at least 3 weeks after the resolution of acute infection (the primary peak in parasitaemia) and is expected to reflect maximum antibody production (Quin and Langhorne, 2001), though measurable responses persist for over 6 months (Achtman et al, 2007). Protocols for this animal work were approved by the UK Home Office
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