Viral kinetics, immunity and transmission of ZIKV: an exploratory analysis in preparation for vaccine development

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Abstract/Summary Our group of researchers has been following subjects with ZIKV infection since 2015 including pregnant and non-pregnant adults, sexual partners of infected women, children and other household contacts as well as infants born to mothers with PCR proven ZIKV infection. We have a database and specimen bank with over 5000 biological specimens available including serial serum and urine specimens from over 356 pregnant women with suspected ZIKV infection, 200 non-pregnant women, 200 sexual partners, 150 household contacts and ZIKV-exposed infants. Other specimens include saliva, placental tissue, amniotic fluid, breast milk and urine, saliva and serum from exposed infants. We hypothesize that viral kinetics of ZIKV including virus load and duration of viral shedding may differ widely between different body compartments including blood, urine, breast milk, amniotic fluid, placenta and saliva, and also may differ between patient populations, including pregnant and non-pregnant patients, sexual partners, children, and infants of ZIKV-infected mothers. We also hypothesize that virus load and pathogenesis may be enhanced by sexual exposure to the virus in addition to vector exposure and that may contribute to enhanced disease morbidity and transmission. We also hypothesize that the development of neutralizing antibodies provides lifelong immunity, but that some individuals, including congenitally infected infants, may have delayed antibody responses with prolonged viral shedding. In adults this might translate not only into prolonged viral shedding and increased transmission risk but also rebound infection. Potentially pre-existing antibodies to other arboviral infections including dengue 1-4 viruses and yellow fever may modify the course of ZIKV infection through interference with viral kinetics or delayed development of neutralizing antibodies. We propose to investigate viral load and viral kinetics in different compartments in distinct populations and correlate findings with severity of symptoms and potential transmission to partners and infants. We will perform plaque reduction neutralization assays in a subset of subjects to investigate protective immunity and potential correlates with viral kinetics, transmission and clearance of infection, and the role of pre-existing antibodies to other flaviviruses.