Prior exposure to flaviviruses may not enhance Zika infection

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Prior dengue or yellow fever infections appear to have no significant effects on subsequent Zika infection, according to new research in monkey models.

It has previously been demonstrated in laboratory studies that antibodies produced from dengue or yellow fever infections can cross-react with Zika without inactivating it. This has raised concerns that prior flavivirus exposure may worsen Zika infections via antibody-dependent enhancement.

The study, published recently in PLoS Pathogens, aimed to characterize the correlation between the in vitro findings and infections in vivo. The researchers, from Walter Reed Army Institute of Research (MD, USA), used 25 rhesus macaques to investigate the effects of prior flavivirus infections. Six of the macaques were previously infected with dengue, five with yellow fever (both ≥420 days prior) and the remaining 14 were flavivirus-naïve.

Before infection with Zika virus, the team collected blood samples to analyze the animal’s antibodies – demonstrating dengue and yellow fever antibodies from previously infected monkeys were cross-reactive with Zika virus in vitro. In addition, they observed that prior exposure promoted increased Zika infection in cell culture assays

However, when assessed in macaques there were no signs of enhanced infection in animals with a history of flavivirus infection. Post-infection analysis of viral titers in blood, urine, cerebrospinal fluid, vaginal secretions and saliva demonstrated no significant differences between macaque groups. Moreover, the team observed that neutralizing antibody levels, biofluid distribution and immune cell kinetics were also similar when comparing previously infected macaques to flavivirus-naïve animals.

These findings suggest that the enhancement assays carried out in vitro may therefore not be predictive of disease severity when translated in rhesus macaque models. However, the researchers caution these results may not apply to humans, and that further clinical data will be necessary.

Lead author, Michael McCracken (Walter Reed Army Institute of Research), concluded: “The study indicates that prior flavivirus immunity is unlikely to impact the safety of a Zika vaccine candidate. Ongoing trials will help inform future vaccine development.”

Sources: McCracken MK, Gromowski GD, Friberg HL et al. Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques. PLoS Pathog. doi:10.1371/journal.ppat.1006487 (2017) (Epub); www.eurekalert.org/pub_releases/2017-08/wrai-pdo080417.php

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