Dengue fever future or investigational therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Overview

Although there is not a commercially available vaccine for dengue, there are several ongoing vaccine development programs. A new recombinant live-attenuated tetravalent dengue vaccine (CYD-TDV) has been investigated for efficacy and safety in a phase III randomized, observer-masked, placebo-controlled, multicenter trial in countries of the Asia-Pacific region. The phase III clinical trial revealed that the novel dengue vaccine is safe and efficacious.[1]

Vaccine Development

There is no commercially available vaccine for the dengue flavivirus. However, a new tetravalent dengue vaccine has been investigated for efficacy and safety in a phase III randomized, observer-masked, placebo-controlled, multicenter trial in countries of the Asia-Pacific region. The novel vaccine is a recombinant live attenuated tetravalent vaccine (CYD-TDV) administered at 0 month, 6 months and 12 months. In the phase III clinical trial, 10275 healthy children 2 to 14 years of age were randomized to either the vaccine or to placebo and were followed up for the occurrence of dengue 28 days after the last vaccine administration.[1]

During a 25 month follow up period, 250 cases of confirmed dengue occurred among subjects enrolled in the study. The incidence of dengue after 28 days of the last vaccination was 1.8% and 4.1% in the vaccinated group and placebo group respectively, leading to an efficacy of the vaccine of 56.5% irrespective of the severity of the disease. The vaccine efficacy was even higher for dengue hemorrhagic fever, reaching 88.5% after 3 doses of the vaccine.[1]

In addition, vaccinated subjects who developed dengue after the vaccine had milder episodes and less rate of hospitalizations compared to unvaccinated subjects. Moreover, the vaccine's efficacy was reported to be higher among subjects who were positive for neutralizing antibodies to dengue at baseline (68% of enrolled children).[1]

Inhibitors of Viral Replication

Emerging evidence suggests that mycophenolic acid and ribivirin inhibit Dengue fever virus replication. Initial experiments showed a fivefold increase in defective viral RNA production by cells treated with each drug.[2] In vivo studies, however, have not yet been done.

References

  1. 1.0 1.1 1.2 1.3 Capeding MR, Tran NH, Hadinegoro SS, Ismail M, Chotpitayasunondh T, Chua MN (2014). Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet.
  2. Takhampunya R, Ubol S, Houng HS, Cameron CE, Padmanabhan R (2006). "Inhibition of dengue virus replication by mycophenolic acid and ribavirin". J Gen Virol. 87 (Pt 7): 1947–52. doi:10.1099/vir.0.81655-0. PMID 16760396.

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