1921
Volume 98, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that IgG reactivity was significantly higher to extracellular and plasma membrane proteins and also correlated positively with both protein abundance and degree of protein polymorphism. Conversely, IgG reactivity was significantly lower to proteins predicted to have human orthologs. These findings provide insight into protein-specific factors that are associated with variability in the magnitude of antibody responses to natural infection—data that could inform vaccine strategies to optimize antibody-mediated immunity as well as the selection of antigens for sero-diagnostic purposes.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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2018-01-10
2018-06-19
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References

  1. Crompton PD, Pierce SK, Miller LH, , 2010. Advances and challenges in malaria vaccine development. J Clin Invest 120: 41684178.
  2. Sercarz EE, Lehmann PV, Ametani A, Benichou G, Miller A, Moudgil K, , 1993. Dominance and crypticity of T cell antigenic determinants. Annu Rev Immunol 11: 729766.
  3. Rao KV, , 1999. Selection in a T-dependent primary humoral response: new insights from polypeptide models. APMIS 107: 807818.
  4. Goldsby RA, Goldsby RA, , 2003. Immunology, 5th edition. New York, NY: W.H. Freeman.
  5. Maizels RM, Clarke JA, Harvey MA, Miller A, Sercarz EE, , 1980. Epitope specificity of the T cell proliferative response to lysozyme: proliferative T cells react predominantly to different determinants from those recognized by B cells. Eur J Immunol 10: 509515.
  6. Kim A, Sadegh-Nasseri S, , 2015. Determinants of immunodominance for CD4 T cells. Curr Opin Immunol 34: 915.
  7. Lazarski CA, Chaves FA, Jenks SA, Wu S, Richards KA, Weaver JM, Sant AJ, , 2005. The kinetic stability of MHC class II: peptide complexes is a key parameter that dictates immunodominance. Immunity 23: 2940.
  8. Yin L, Calvo-Calle JM, Dominguez-Amorocho O, Stern LJ, , 2012. HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives. J Immunol 189: 39833994.
  9. Poluektov YO, Kim A, Hartman IZ, Sadegh-Nasseri S, , 2013. HLA-DO as the optimizer of epitope selection for MHC class II antigen presentation. PLoS One 8: e71228.
  10. Kedl RM, Kappler JW, Marrack P, , 2003. Epitope dominance, competition and T cell affinity maturation. Curr Opin Immunol 15: 120127.
  11. Kunnath-Velayudhan S, 2010. Dynamic antibody responses to the Mycobacterium tuberculosis proteome. Proc Natl Acad Sci USA 107: 1470314708.
  12. Liang L, 2011. Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans. J Proteome Res 10: 48134824.
  13. Seder RA, VRC 312 Study Team.; , 2013. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341: 13591365.
  14. Khan SM, Janse CJ, Kappe SH, Mikolajczak SA, , 2012. Genetic engineering of attenuated malaria parasites for vaccination. Curr Opin Biotechnol 23: 908916.
  15. Good MF, 2013. Cross-species malaria immunity induced by chemically attenuated parasites. J Clin Invest. 123: 33533362.
  16. Bijker EM, 2013. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci USA 110: 78627867.
  17. Crompton PD, 2010. A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci USA 107: 69586963.
  18. Aurrecoechea C, 2009. PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res 37: D539D543.
  19. Logan-Klumpler FJ, 2012. GeneDB – an annotation database for pathogens. Nucleic Acids Res 40: D98D108.
  20. Tran TM, 2013. An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection. Clin Infect Dis 57: 4047.
  21. Davies DH, 2005. Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci USA 102: 547552.
  22. Shimp RL, Jr 2013. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle. Vaccine 31: 29542962.
  23. Sboner A, Karpikov A, Chen G, Smith M, Mattoon D, Freeman-Cook L, Schweitzer B, Gerstein MB, , 2009. Robust-linear-model normalization to reduce technical variability in functional protein microarrays. J Proteome Res 8: 54515464.
  24. Boyle EI, Weng S, Gollub J, Jin H, Botstein D, Cherry JM, Sherlock G, , 2004. GO::TermFinder – open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics 20: 37103715.
  25. Harris MA, Gene Ontology Consortium.; , 2004. The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res 32: D258D261.
  26. Chen F, Mackey AJ, Stoeckert CJ, Jr Roos DS, , 2006. OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res 34: D363D368.
  27. Benaglia T, Chauveau D, Hunter DR, Young D, , 2009. mixtools: an R package for analyzing finite mixture models. J Stat Softw 32: 129.
  28. Bates, D, Maechler M, Bolker B, Walker S, , 2015. Fitting linear mixed-effects models using lme4. J Stat Soft 67: 148.
  29. Smith JD, Rowe JA, Higgins MK, Lavstsen T, , 2013. Malaria’s deadly grip: cytoadhesion of Plasmodium falciparum-infected erythrocytes. Cell Microbiol 15: 19761983.
  30. Haddad D, Liljeqvist S, Kumar S, Hansson M, Stahl S, Perlmann H, Perlmann P, Berzins K, , 1995. Surface display compared to periplasmic expression of a malarial antigen in Salmonella typhimurium and its implications for immunogenicity. FEMS Immunol Med Microbiol 12: 175186.
  31. Scherle PA, Gerhard W, , 1988. Differential ability of B cells specific for external vs. internal influenza virus proteins to respond to help from influenza virus-specific T-cell clones in vivo. Proc Natl Acad Sci USA 85: 44464450.
  32. Mayer C, Slater L, Erat MC, Konrat R, Vakonakis I, , 2012. Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. J Biol Chem 287: 71827189.
  33. Yilmaz B, 2014. Gut microbiota elicits a protective immune response against malaria transmission. Cell 159: 12771289.
  34. Korepanova A, Gao FP, Hua Y, Qin H, Nakamoto RK, Cross TA, , 2005. Cloning and expression of multiple integral membrane proteins from Mycobacterium tuberculosis in Escherichia coli. Protein Sci 14: 148158.
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Supplementary Data

Supplemental Figure

  • Received : 05 Jun 2017
  • Accepted : 11 Sep 2017

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