Zika virus (ZIKV) is a mosquito-borne flavivirus that was first identified in Uganda in 1947 in monkeys. Outbreaks of ZIKV disease have been recorded in Africa, the Americas, Asia and the Pacific. Outbreak of ZIKV disease was reported from the Island of Yap (Federated States of Micronesia) in 2007, followed by a large outbreak of ZIKV infection in French Polynesia in 2013 and other countries and territories in the Pacific.
In March 2015, Brazil reported a large outbreak of rash illness, soon identified as ZIKV infection, and in July 2015, found to be associated with Guillain-Barré. syndrome. In October 2015, Brazil reported an association between ZIKV infection and microcephaly. Outbreaks and evidence of transmission soon appeared throughout the Americas, Africa, and other regions of the world.To date, more than 80 countries and territories have reported evidence of mosquito-transmitted ZIKV infection.
In Malaysia, the ZIKV has been isolated in Aedes aegypti mosquitoes in 1960s. The first ZIKV case in Malaysia was officially reported in September 2016; a Malaysian woman with fever and facial rash a week after returning from a visit to Singapore, tested positive for ZIKV. The first local infection was detected in a 61-year-old man from Kota Kinabalu. In Malaysia, ZIKV infection was not widespread compared to outbreaks in countries nearby such as Singapore and Thailand, and to date the number of laboratory confirmed cases is eight.
The risk of congenital malformations following infection in pregnancy remains unknown. An estimated 5–15% of infants born to women infected with ZIKV during pregnancy have evidence of ZIKV-related complications. Congenital malformations occur following both symptomatic and asymptomatic infection.
There is no treatment available for ZIKV infection or its associated diseases. The public health value proposition for a Zika vaccine is to prevent prenatal ZIKV infection and congenital ZIKV syndrome, resulting in microcephaly, other nervous system malformations and pregnancy-related complications.
Therefore, the immunisation of women of reproductive age, including pregnant women, is considered to be of highest priority. In addition to vulnerability during the first trimester, evidence is accumulating that ZIKV infection in the 2nd and 3rd trimesters can also lead to adverse fetal and post-natal outcomes.
Currently no vaccine is registered. Various vaccine candidates have been developed and are in various stages of preclinical and clinical development. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralising antibodies, although these varied by vaccine candidate and dosing regimen
i. DNA vaccine developed by NIAID’s Vaccine Research Center (VRC) has been approved for Phase 2 clinical trials in humans. The strategy is similar to the investigational flavivirus vaccine for West Nile virus infection. The vaccine consists of a DNA plasmid encoding the E and PrM proteins which make up the outer protein coat of the Zika virion. Results of Phase 1 trials indicate the optimised vaccine is safe and able to induce a neutralising antibody response against ZIKV virus.
A Phase 2 clinical trial (VRC 705) was launched in 2017, which enrolled healthy adult and adolescent participants in areas of confirmed or potential active mosquito-transmitted ZIKV infection. The trial further evaluates the safety and immunogenicity of the vaccine and will assess the optimal dose for administration. It will also attempt to determine if the vaccine can effectively prevent disease caused by ZIKV infection.
ii. A modified mRNA vaccine developed in collaboration with Moderna Therapeutics containing the E and PrM proteins is undergoing concurrent phase 1 and 2 clinical trials.
iii. A live attenuated vaccine, rZIKV/D4Δ30-713 is undergoing phase 1 clinical trials. This vaccine is based on the dengue vaccine Dengvaxia (NIH, NIAID, US). The chimeric virus consists of a dengue virus type 4 backbone that expresses ZIKV surface proteins.
iv. A purified inactivated vaccine (ZPIV) is currently under development by the Walter Reed Army Institute of Research (WRAIR). This vaccine is based on the same technology used to develop a vaccine against Japanese Encephalitis Virus.
v. Multiple vaccines are also being developed using safe, non-pathogenic, viruses as vectors for immunogenic ZIKV proteins. One phase 1 trial is using the Measles virus as a vector and was completed in April 2018. Another vaccine platform makes use of Adenovirus as a vector and phase 1 studies will be complete in 2019
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