Clinical Pearls & Morning Reports

By Carla Rothaus

Published October 9, 2019


Are vaccines against ZIKV in development?

Zika virus (ZIKV) is a positive-sense RNA flavivirus in the family Flaviviridae, which also includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses. The ability of ZIKV to cause congenital defects in fetuses and infants, as exemplified by the microcephaly epidemic in Brazil, is an unprecedented feature in a mosquito-borne viral infection. The ZIKV pandemic has waned, but the virus still poses a public health threat, as shown by continued reports of outbreaks in Asia, India, and Africa. Read the Review Article here.

Clinical Pearls

Q: Is ZIKV still spreading in the Americas?

A: ZIKV transmission may be occurring without an identifiable outbreak, since the majority of infections are asymptomatic. The identification of a large and unreported outbreak in Cuba in 2017, with cases still being identified in 2018, suggests that ZIKV may still be spreading silently in the Americas. At present, there is no evidence of a nonprimate animal reservoir for ZIKV. However, another concern, supported by the detection of ZIKV RNA in Brazilian monkeys living in proximity to humans, is the possibility that ZIKV will establish a zoonotic cycle in the Americas. This would be akin to what occurred with the introduction of yellow fever to the Americas in the 17th century and would serve as a focus for future spillover infection to humans.

Q: Does previous exposure to flaviviruses affect the course of ZIKV infection?

A: The effect of preexisting immunity against flaviviruses on ZIKV infection outcomes — whether the immunity is elicited by infection or by immunization with flavivirus vaccines — is a matter of debate. Laboratory investigations have yielded contradictory findings with respect to whether dengue infection elicits an immune response that protects against ZIKV infection or exacerbates infection by way of antibody-dependent enhancement.

Morning Report Questions

Q: What are some of the important current knowledge gaps regarding ZIKV infection?

A: Although the pandemic yielded a large body of information about ZIKV, important knowledge gaps remain. Still unknown is whether the ZIKV-associated complications that were identified during the pandemic were new emerging phenomena — perhaps caused by the virus acquiring enhanced fitness, transmissibility, or disease severity phenotype — or had occurred previously but went undetected because of limited surveillance or infrequent transmission. Data from in vitro studies and experimental studies in animals suggest that ZIKV mutations may increase the infectiousness of the virus in the A. aegypti vector and the risk of fetal microcephaly. However, birth defects have been associated with infections by strains that do not contain these mutations, and pathogen-specific markers that predict the risk of birth defects have not been identified. Current diagnostic testing remains suboptimal for the detection of congenital ZIKV infections, which in turns hampers implementation of clinical management. 

Q: Are vaccines against ZIKV in development?

A: Several compounds have shown activity against ZIKV in vitro, but none of them have yet been evaluated in clinical trials. Since no antiviral agents have been approved by regulatory agencies for the treatment of ZIKV infection, the clinical management of acute ZIKV infection is supportive care. More than 10 candidate vaccines have advanced to phase 1 clinical trials and 1 has begun phase 2 clinical trials. However, a major barrier to evaluating vaccine effectiveness is the waning incidence of ZIKV after the pandemic, which in turn has hampered implementation of phase 2 and phase 3 clinical trials.

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