| dc.description.abstract | Dengue infections have been common in Sri
Lankan since 1989 when the first epidemic of
>1200 cases, was reported by the Ministry of
Health (MoH). My work in dengue began after
I returned to Sri Lanka in 2007 and oversaw the
laboratory component of the Pediatric Dengue
Surveillance project in collaboration with the
MoH. Then in collaboration with Prof Alex
Sette and Prof Aravinda de Silva of the US, a
National Institutes of Health (NIH)- USA, funded
project was initiated to expand the knowledge
of the human T cell response against dengue
in the context of the larger immune response.
Lymphocytes being discarded from blood donors
at the National Blood Bank, Sri Lanka, were used
after ethical review committee and MoH approvals
to identify possible new epitopes in the context
of the Sri Lankan population. The lymphocytes
were screened for past dengue infections and
used to validate the 8000+ potential peptide
pool generated using bioinformatics. Validating
the peptides by testing lymphocytes from past
dengue infected blood donors added ~300 new
dengue T cell epitope peptides to the literature.
One major discovery highlighted the importance
of the dengue non-structural proteins in the T
cell immune response against dengue infections.
This new pool of peptides has been used to study
the immune responses being generated by new
dengue vaccines. Our data suggest that the nonstructural
(NS) proteins of dengue are largely
responsible for the human T cell response and this
may explain the lack of protection in the recently
WHO approved Dengvaxia dengue vaccine,
which lacks the dengue NS proteins. Furthermore,
our data show that the immune response from
the yet to be approved NIH/Butantan vaccine is
similar to the natural infection and may provide
better protection. In addition, this international
project has helped understand the role of T
cells in the overall human immune response in
controlling a dengue infection. | en_US |
