such as "Introduction", "Conclusion"..etc
Saima Khanam , Pilankatta Rajendra , Navin Khanna and Sathyamangalam Swaminathan
Group, International Centre for Genetic Engineering &
Biotechnology, PO Box 10504, Aruna Asaf Ali Marg, New Delhi 110016,
BMC Biotechnology 2007,
7:10doi:10.1186/1472-6750-7-10. Open Access article distributed under the terms of the Creative Commons Attribution License.
Dengue is a public health problem of global significance for which
there is neither an effective antiviral therapy nor a preventive
vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN)
viruses, which are members of the Flaviviridae family. There
are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each
of which is capable of causing disease. As immunity to any one serotype
can potentially sensitize an individual to severe disease during
exposure to a heterologous serotype, the general consensus is that an
effective vaccine should be tetravalent, that is, it must be capable of
affording protection against all four serotypes. The current strategy
of creating tetravalent vaccine formulations by mixing together four
monovalent live attenuated vaccine viruses has revealed the phenomenon
of viral interference leading to the manifestation of immune responses
biased towards a single serotype.
This work stems from the emergence of (i) the DEN virus envelope (E)
domain III (EDIII) as the most important region of the molecule from a
vaccine perspective and (ii) the adenovirus (Ad) as a promising vaccine
vector platform. We describe the construction of a recombinant,
replication-defective Ad (rAd) vector encoding a chimeric antigen made
of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this
rAd vector, in conjunction with a plasmid vector encoding the same
chimeric bivalent antigen, in a prime-boost strategy, we show that it
is possible to elicit equipotent neutralizing and T cell responses
specific to both DEN serotypes 2 and 4.
Our data support the hypothesis that a DEN vaccine targeting more
than one serotype may be based on a single DNA-based vector to
circumvent viral interference. This work lays the foundation for
developing a single Ad vector encoding EDIIIs of all four DEN serotypes
to evoke a balanced immune response against each one of them. Thus,
this work has implications for the development of safe and effective
tetravalent dengue vaccines.
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