TY - JOUR
T1 - Quantifying variation in the potential for antibody-mediated apparent competition among nine genotypes of the rodent malaria parasite Plasmodium chabaudi
AU - Fairlie-Clarke, Karen J.
AU - Allen, Judith E.
AU - Read, Andrew F.
AU - Graham, Andrea Linn
N1 - Funding Information:
This work was supported by the BBSRC (BB/C508734/1 to J.E.A., A.F.R. and A.L.G.) and the Wellcome Trust (068292/Z/01/Z to A.F.R.). A.L.G. also acknowledges the support of the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center. The authors thank J. Langhorne and R. Anders for recombinant antigens, and D. Cavanagh, M. Siva-Jothy, G. H. Long, A. B. Pedersen & N. Mideo for comments on the draft manuscript.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - Antibody
KW - Cross-reactivity
KW - Mixed infection
KW - Plasmodium chabaudi
KW - Virulence evolution
KW - Within-host competition
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U2 - 10.1016/j.meegid.2013.09.013
DO - 10.1016/j.meegid.2013.09.013
M3 - Article
C2 - 24056014
AN - SCOPUS:84885070747
SN - 1567-1348
VL - 20
SP - 270
EP - 275
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -