Autor/a:
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Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T.
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Abstract:
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The Brighton Collaboration Viral Vector Vaccines Safety Working
Group (V3SWG) was formed to evaluate the safety of live,
recombinant viral vaccines incorporating genes from heterologous
viruses inserted into the backbone of another virus (so-called
"chimeric virus vaccines"). Many viral vector vaccines are in
advanced clinical trials. The first such vaccine to be approved
for marketing (to date in Australia, Thailand, Malaysia, and the
Philippines) is a vaccine against the flavivirus, Japanese
encephalitis (JE), which employs a licensed vaccine (yellow
fever 17D) as a vector. In this vaccine, two envelope proteins
(prM-E) of YF 17D virus were exchanged for the corresponding
genes of JE virus, with additional attenuating mutations
incorporated into the JE gene inserts. Similar vaccines have
been constructed by inserting prM-E genes of dengue and West
Nile into YF 17D virus and are in late stage clinical studies.
The dengue vaccine is, however, more complex in that it requires
a mixture of four live vectors each expressing one of the four
dengue serotypes. This vaccine has been evaluated in multiple
clinical trials. No significant safety concerns have been found.
The Phase 3 trials met their endpoints in terms of overall
reduction of confirmed dengue fever, and, most importantly a
significant reduction in severe dengue and hospitalization due
to dengue. However, based on results that have been published so
far, efficacy in preventing serotype 2 infection is less than
that for the other three serotypes. In the development of these
chimeric vaccines, an important series of comparative studies of
safety and efficacy were made using the parental YF 17D vaccine
virus as a benchmark. In this paper, we use a standardized
template describing the key characteristics of the novel
flavivirus vaccine vectors, in comparison to the parental YF 17D
vaccine. The template facilitates scientific discourse among key
stakeholders by increasing the transparency and comparability of
information. The Brighton Collaboration V3SWG template may also
be useful as a guide to the evaluation of other recombinant
viral vector vaccines. |