New Study Findings on Dengue Could Throw a Wrench in Current Zika Research

With multiple Zika virus vaccines already in the works, a group of researchers has an important suggestion: consider previous infection with dengue in the development of any new prophylactic modality.

In a study published on August 18, 2017 in the journal Science Immunology, a team of authors from the Scripps Research Institute in La Jolla, California and the Ragon Institute at Massachusetts General Hospital in Boston, Massachusetts sought to clarify the relationship between the 2 mosquito-borne viruses, both of which have created significant public health challenges in the Caribbean and South America in recent years. Both dengue and Zika are, of course, carried by the Aedes aegypti mosquito.

Using earlier research that has confirmed that the 2 viruses “share a high degree of homology,” with dengue virus as a starting point, the research team, which previously published several notable studies on Zika, hoped to establish whether this relationship could impact immunity and immune response between them—specifically, they wanted to determine whether preexisting immunity to dengue could affect immune responses to Zika. To do so, they tracked the evolution of Zika-induced B cell responses in 3 dengue-experienced donors and compared them to the immune response in 1 dengue-naïve donor.

In general, they found that, in the study subjects with a history of dengue, plasmablast antibody responses featured “relatively high” somatic hypermutation and a “bias toward” dengue virus binding and neutralization. The authors believe this finding implies that there is an early activation of dengue virus clones in new Zika infections. Notably, 5 months following Zika infection, the 3 dengue-experienced donors developed potent type-specific Zika virus neutralizing antibody responses in addition to dengue virus cross-reactive responses. Conversely, the dengue-naïve donor had what the authors described as a “classical primary plasmablast response.”

“Our findings show that cross-reactive, weakly neutralizing dengue antibodies are recalled in response to Zika infection, particularly during early infection,” study co-authors Dennis R. Burton, PhD, and Laura M. Walker, PhD, both of the Scripps Institute, said in an email to Contagion^®. Dr. Burton heads up his own lab at Scripps, which has been the research site for a number of important Zika-related studies since the beginning of 2016. He is also the James & Jessie Minor Chair in Immunology at Scripps. Dr. Walker is Associate Director, Adimab, LLC in Boston.

In addition, because cross-reactive responses were “poorly neutralizing” and associated with enhanced Zika infection in vitro, the authors believe that their findings illustrate that preexisting immunity to dengue virus could “negatively affect protective antibody responses” to Zika.

“These antibodies do not prevent the elicitation of potently neutralizing Zika-specific antibodies during convalescence,” Drs. Burton and Walker added. “So, the first antibodies after Zika infection in dengue-experienced donors are poor and may even be detrimental, but if one waits, then eventually effective anti-Zika antibodies emerge.”

What are the implications of these findings for ongoing Zika vaccine development? The Scripps/Ragon team believe their results suggest that those involved in vaccine trials may need to effectively go back to the drawing board. In their email to Contagion^®, the authors noted, “Our findings suggest that vaccines should be designed to preferentially induce antibodies that bind to Zika-specific epitopes and to minimize the induction of the cross-reactive antibodies. [We] do not believe current vaccines are so designed and so we are arguing for a rethink.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.