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ABSTRACT
Dengue virus is the leading cause of vector-borne viral disease with four serotypes in circulation. Vaccine development has been complicated by the potential for both protection and disease enhancement during heterologous infection. Secondary infection triggers cross-reactive immune memory responses that have varying functional and epitope specificities that determine protection or risk. Strongly neutralizing antibodies to quaternary epitopes may be especially important for virus neutralization. Cell-mediated immunity dominated by Th1 functions may also play an important role. Determining an immune correlate of protection or risk would be highly beneficial for vaccine development but is hampered by mechanistic uncertainties and assay limitations. Clinical efficacy trials and human infection models along with a systems approach may provide future opportunities to elucidate such correlates.
Acknowledgement
The authors thank Nopporn Sittisombut for critical reading of the manuscript.
Financial & competing interests disclosure
This work was supported in part by the National Institutes of Health (grant P01 AI034533) and the Bill and Melinda Gates Foundation (grant OPP1053432). The opinions expressed are those of the authors and do not represent the official position of the National Institutes of Health or the Bill and Melinda Gates Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.