Humoral cross-reactivity between Zika and dengue viruses: implications for protection and pathology Open

Lalita Priyamvada1,2, William Hudson2,3, Rafi Ahmed2,3 and Jens Wrammert1,2

  1. Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA
  2. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
  3. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA

Correspondence: J Wrammert, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Received 18 February 2017; Revised 3 April 2017; Accepted 17 April 2017


Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that has recently caused extensive outbreaks in Central and South America and the Caribbean. Given its association with Guillain-Barr Syndrome in adults and neurological and ocular malformities in neonates, ZIKV has become a pathogen of significant public health concern worldwide. ZIKV shares a considerable degree of genetic identity and structural homology with other flaviviruses, including dengue virus (DENV).

In particular, the surface glycoprotein envelope (E), which is involved in viral fusion and entry and is therefore a chief target for neutralizing antibody responses, contains regions that are highly conserved between the two viruses. This results in immunological cross-reactivity, which in the context of prior DENV exposure, may have significant implications for the generation of immune responses to ZIKV and affect disease outcomes. Here we address the issue of humoral cross-reactivity between DENV and ZIKV, reviewing the evidence for and discussing the potential impact of this cross-recognition on the functional quality of antibody responses against ZIKV. These considerations are both timely and relevant to future vaccine design efforts, in view of the existing overlap in the distribution of ZIKV and DENV and the likely spread of ZIKV to additional DENV-naive and experienced populations.

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