Dengue virus becomes resistant to certain vaccines
While searching for a new approach in vaccine development for dengue,
researchers discovered that the dengue virus changes its shape through
mutations in envelope protein to evade vaccines and therapeutics.
DENV2 (a dengue virus) exists as smooth spherical surface particles while
growing at the mosquito's physiological temperature (29 degrees Celsius). It
then changes to bumpy surfaced particles at human physiological temperature (37
degrees Celsius).
This ability to morph helps the virus to evade the immune system of the
human host. Hence, understanding the mechanism behind this is important for
therapeutics and vaccine development, reported the study.
"Together with Professor Pei-Yong Shi from UTMB, we found that in
laboratory-developed DENV2 strains, mutations in the virus' E protein causes
its transformation into bumpy particles. These structural changes can cause
vaccines and therapeutics to be ineffective against the virus," said Ms
Xin-Ni Lim, the study's lead author who is from Duke-NUS' Emerging Infectious
Diseases (EID) Programme.
The team also tested four DENV2 strains obtained from patients. They
observed that in contrast to the laboratory-adapted viruses, the majority of
these clinical strains maintained smooth surface structure at 37 degrees
Celsius.
However, at 40 degrees Celsius, the temperature of a fever, all virus
strains took on a bumpy surface.
"Our study gives a new direction to vaccine development and treatment
for dengue disease. For prevention of disease through vaccines that are
administered to the patient before dengue infection, we should use those that
are effective against the smooth surface virus," said Dr Sheemei Lok,
Professor, Duke-NUS' EID and corresponding author of this study.
"When it comes to patients displaying fever symptoms, treatment
strategies effective against the bumpy surface particles should be
implemented," added Dr Lok.
"This study is a first step towards gaining more insight into how
DENV2 reacts and adapts to the host's immunological defences. We were also able
to use computational modelling approaches to predict why particles from
different DENV2 strains are more or less adept at morphing from the smooth to
bumpy structures. By better understanding the interactions between the virus
and the host, we will be able to develop better therapies and vaccines to treat
or prevent infections, and contribute to public health outcomes," said Dr
Peter Bond, Principal Investigator from A*STAR's BII.
The study's findings also show that the lab adapted DENV2 may not be a good
model for research, as its structure is different from the clinical strains
isolated from patients. The team is planning to study the other DENV serotypes
to find out if there are any other possible structural changes.