Research ArticleMalaria

Targeting TLRs Expands the Antibody Repertoire in Response to a Malaria Vaccine

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Science Translational Medicine  27 Jul 2011:
Vol. 3, Issue 93, pp. 93ra69
DOI: 10.1126/scitranslmed.3002135

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Sometimes one very talented athlete can carry a team to a championship. Yet, not even the best athletes can reach their full potential without the support of their teammates. Similarly, successful vaccines require strong and specific pathogen-derived antigens, but frequently, one of these essential players is not multitalented enough to elicit a protective immune response. To do so, these stars require help—which comes in the form of adjuvants. Whereas specific antigens induce a slower but pathogen-restricted immune response, adjuvants activate the faster but more general innate immune system. The addition of adjuvants to vaccine formulations is known to improve the quality, strength, and duration of the immune response by somewhat nebulous mechanisms. Now, Wiley et al. use massively parallel sequencing to quantify the immune response to a malarial antigen and find that a little help from an adjuvant results in added antibody diversity.

The authors showed that adding a Toll-like receptor 4 agonist, which turns on a pattern-recognition receptor that activates innate immune cells, to a commonly used oil-in-water adjuvant in an antimalaria vaccine formulation greatly increased the diversity of antibodies made in response to the vaccine. These antibodies were better able to neutralize and could respond to more variants of the antigen. Therefore, in the context of an infection, these adjuvanted vaccines should be able to successfully fight more strains of a pathogen. What’s more, the sequencing method used by Wiley et al. should be broadly applicable to the characterization of immune responses to other vaccines and to infections, thus leading to improvements in the detection, diagnosis, and treatment of various diseases. Furthermore, this strategy can be used to scout out adjuvants that make the best teammates for pathogen-specific antigens in vaccine formulations.


  • * These authors contributed equally to this work.

  • Citation: S. R. Wiley, V. S. Raman, A. Desbien, H. R. Bailor, R. Bhardwaj, A. R. Shakri, S. G. Reed, C. E. Chitnis, D. Carter, Targeting TLRs Expands the Antibody Repertoire in Response to a Malaria Vaccine. Sci. Transl. Med. 3, 93ra69 (2011).

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