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- Balasingam, Shobana, et al.
(författare)
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Randomized controlled trials for influenza drugs and vaccines : a review of controlled human infection studies
- 2016
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Ingår i: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 49, s. 18-29
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Controlled human infection, the intentional infection of healthy volunteers, allows disease pathogenesis to be studied and vaccines and therapeutic interventions to be evaluated in a controlled setting. A systematic review of randomized controlled trials of countermeasures for influenza that used the experimental human infection platform was performed. The primary objective was to document the scope of trials performed to date and the main efficacy outcome in the trials. The secondary objective was to assess safety and identify serious adverse events.METHODS: The PubMed database was searched for randomized controlled influenza human challenge studies with predetermined search terms. Review papers, papers without outcomes, community-acquired infections, duplicated data, pathogenesis studies, and observational studies were excluded.RESULTS: Twenty-six randomized controlled trials published between 1947 and 2014 fit the study inclusion criteria. Two-thirds of these trials investigated antivirals and one-third investigated influenza vaccines. Among 2462 subjects inoculated with influenza virus, the incidence of serious adverse events was low (0.04%). These challenge studies helped to down-select three antivirals and one vaccine that were subsequently approved by the US Food and Drug Administration (FDA).CONCLUSIONS: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.
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| 2. |
- Velumani, Sumathy, et al.
(författare)
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Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees
- 2016
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Ingår i: Human Vaccines & Immunotherapeutics. - : Taylor & Francis. - 2164-5515 .- 2164-554X. ; 12:5, s. 1265-1273
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Tidskriftsartikel (refereegranskat)abstract
- Globally, dengue virus (DENV) is one of the most widespread vector-borne viruses. Dengue disease affects populations in endemic areas and, increasingly, tourists who travel to these countries, but there is currently no approved vaccine for dengue. A phase 3 efficacy trial with Sanofi-Pasteur's recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) conducted in South East Asia showed an overall efficacy of 56% against virologically confirmed dengue infections of any severity and any of the 4 serotypes, but the long-term protection of the vaccine has yet to be demonstrated. To address longevity of antibody titers and B cell memory, we recalled study participants from an earlier CYD immunogenicity study (Phase 2) conducted in Singapore that enrolled healthy volunteers in the year 2009. Depending on the age group, 57-84% of the participants initially generated a neutralizing antibody titer ≥ 10 to all 4 DENV serotypes 28 d after the third and final dose. We observed very low antibody titers in blood samples collected from 23 vaccinees 5 y after the first dose, particularly titers of antibodies binding to virus particles compared with those binding to recombinant E protein. The in vivo efficacy of plasma antibodies against DENV-2 challenge was also tested in a mouse model, which found that only 2 out of 23 samples were able to reduce viremia. Although the sample size is too small for general conclusions, dengue immune memory after vaccination with CYD-TDV appears relatively low.
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