(498c) Measures and Models for Production of Zika Virus Vaccines

Since the discovery of its African lineage in Uganda in 1947, Zika virus was largely neglected because most of its infections in humans caused only mild or minimal symptoms. However, since 2014, outbreaks of an Asian lineage of Zika have been linked to neurological disorders in adults and congenital defects in newborns. So far 3720 cases of congenital Zika syndrome have been reported in the Americas. In addition, Zika virus has differed from related viruses, such as Dengue, West Nile and Japanese encephalitis virus in displaying direct human-to-human transmission. The resulting threat of Zika virus to human health has prompted the development of new vaccines. A few live- attenuated vaccines and purified inactivated vaccines, which can elicit a robust immune response without a booster, have entered clinical trials. Once such a vaccine is approved for clinical use, large-scale production of the vaccine would be necessary to control an outbreak. To date, little data has been collected to guide such large-scale production. Here, we infected Vero cells adhesively cultured in well-plates with two Zika virus strains: one cell-culture-adapted strain from the African lineage and one recently isolated strain from the Asian lineage, to study vaccine production. At different time points post-infection, released virus particles were measured from the supernatant and within-cell expression of the viral envelope protein was quantified by immunocytochemical staining. A mathematical model for cell infection and virus production was developed to estimate parameters and guide vaccine production. The African-lineage strain was found to produce a 10-fold higher yield than the Asian-lineage strain, and the measured half-lives at physiological temperature were less than 2 hours for both the African and Asian lineage strains, exhibiting low stability compared to many others viruses. In summary, for vaccine production, the African-lineage strain is slightly more stable and produces significantly higher yields.