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BIOLOGY 20 General Biology
Task:
Introduction
Daily more than a million people are infected with any of the four distinct serotypes of dengue viruses (DENV-1, −2, −3, and, −4). The world needs a dengue vaccine for all age groups, regardless of whether they may, or may not have been previously exposed to one of the four dengue viruses. In 2019, Sanofi Pasteur’s Dengvaxia, a live attenuated tetravalent dengue vaccine, whichdoes not give complete protection, after a three-dose regimen spread over 1 year (Arredondo-García et al., 2018; Thomas and Y oon, 2019), was granted a limited approval by the United States Food and Drug Administration. This approval was for its use in 9–16 year-old children with laboratory-confirmed previous dengue infection, living in dengue-endemic areas (United States Food & Drug, 2019). Efficacy trials of Dengvaxia in several dengue-endemic countries of Asia and Latin America, in ∼35,000 2–16 year-old children (Sabchareon et al., 2012; Capeding et al., 2014; Villar et al., 2015), showed that vaccine efficacy (VE) i.e., the capacity to prevent symptomatic virologically confirmed dengue (VCD), varied by serotype, and was the lowest against DENV2. Overall VE was 65.6% (95% CI 60.7–69.9) in 9–16 year olds, while in 2–8 year olds it was 44.6% (95% CI 31.6–55), at 2 years following administration of the first dose of the vaccine. At 3 years post-dose 1, vaccinated children in the 2–5 year age group, were found to be nearly 8 times likely to be hospitalized for severe dengue, compared to children in the placebo group (Hadinegoro et al., 2015). VE was subsequently found to be related to the pre-vaccination serostatus of the trial subjects.
While VE against VCD at 2 years post-dose 1 was 76% (95% CI 64–84) in >9 year-old children, who had been exposed to dengue infection before vaccination (seropositive), it was only 39% (95% CI−1 to 63) in children who were dengue-naïve (seronegative) at the beginning of the trial (Sridhar et al., 2018). Long-term follow-up studies until 5 years reveal that in seronegative recipients, there is increased risk of severe dengue from the 3rd year onwards, postdose 1. Clearly, developing a safe and efficacious dengue vaccine constitutes quite a formidable challenge. Several unique factors, associated with the biology, and pathogenesis of dengue, taken together with lessons of the Dengvaxia experience, necessitates exploring alternate dengue vaccine development options.
There are additional whole virus-based dengue vaccines in advance stages of clinical trials (Clinicaltrials.gov, 2020; Tricou et al., 2020). Moreover, a few recombinant dengue vaccine candidates are also at various stages of development (Vannice et al., 2015; Swaminathan and Khanna, 2019; Deng et al., 2020). It is great that the pipeline of dengue vaccines continue to increase. A safe and effective dengue vaccine could soon become a reality.
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