A
new nanoparticle vaccine developed by MIT researchers could assist efforts to
eradicate polio worldwide. The vaccine, which delivers multiple doses in just
one injection, could make it easier to immunize children in remote regions of
Pakistan and other countries where the disease is still found.
While
the number of reported cases of polio dropped by 99 percent worldwide between
1988 and 2013, according to the Centers for Disease Control, the disease has
not been completely eradicated, in part because of the difficulty in reaching
children in remote areas to give them the two to four polio vaccine injections
required to build up immunity.
“Having
a one-shot vaccine that can elicit full protection could be very valuable in
being able to achieve eradication,” says Ana Jaklenec, a research scientist at
MIT’s Koch Institute for Integrative Cancer Research and one of the senior
authors of the paper.
Robert
Langer, the David H. Koch Institute Professor at MIT, is also a senior author
of the study, which appears in the Proceedings of the National Academy of
Sciences the week of May 21. Stephany Tzeng, a former MIT postdoc who is now a
research associate at Johns Hopkins University School of Medicine, is the
paper’s lead author.
“We
are very excited about the approaches and results in this paper, which I hope
will someday lead to better vaccines for patients around the world,” Langer
says.
There
are no drugs against poliovirus, and in about 1 percent of cases, it enters the
nervous system, where it can cause paralysis. The first polio vaccine, also
called the Salk vaccine, was developed in the 1950s. This vaccine consists of
an inactivated version of the virus, which is usually given as a series of two
to four injections, beginning at 2 months of age. In 1961, an oral vaccine was
developed, which offers some protection with only one dose but is more
effective with two to three doses.
The
oral vaccine, which consists of a virus that has reduced virulence but is still
viable, has been phased out in most countries because in very rare cases, it
can mutate to a virulent form and cause infection. It is still used in some
developing countries, however, because it is easier to administer the drops
than to reach children for multiple injections of the Salk vaccine.
For
polio eradication efforts to succeed, the oral vaccine must be completely
phased out, to eliminate the chance of the virus reactivating in an immunized
person. Several years ago, Langer’s lab received funding from the Bill and
Melinda Gates Foundation to try to develop an injectable vaccine that could be
given just once but carry multiple doses.
“The
goal is to ensure that everyone globally is immunized,” Jaklenec says.
“Children in some of these hard-to-reach developing world locations tend to not
get the full series of shots necessary for protection.”
To
create a single-injection vaccine, the MIT team encapsulated the inactivated
polio vaccine in a biodegradable polymer known as PLGA. This polymer can be
designed to degrade after a certain period of time, allowing the researchers to
control when the vaccine is released.
“There’s
always a little bit of vaccine that’s left on the surface or very close to the
surface of the particle, and as soon as we put it in the body, whatever is at
the surface can just diffuse away. That’s the initial burst,” Tzeng says. “Then
the particles sit at the injection site and over time, as the polymer degrades,
they release the vaccine in bursts at defined time points, based on the degradation
rate of the polymer.”
The
researchers had to overcome one major obstacle that has stymied previous
efforts to use PLGA for polio vaccine delivery: The polymer breaks down into
byproducts called glycolic acid and lactic acid, and these acids can harm the
virus so that it no longer provokes the right kind of antibody response.
To
prevent this from happening, the MIT team added positively charged polymers to
their particles. These polymers act as “proton sponges,” sopping up extra
protons and making the environment less acidic, allowing the virus to remain
stable in the body.
In
the PNAS study, the researchers designed particles that would deliver an
initial burst at the time of injection, followed by a second release about 25
days later. They injected the particles into rats, then sent blood samples from
the immunized rats to the Centers for Disease Control for testing. Those
studies revealed that the blood samples from rats immunized with the
single-injection particle vaccine had an antibody response against poliovirus
just as strong as, or stronger than, antibodies from rats that received two
injections of Salk polio vaccine.
To
deliver more than two doses, the researchers say they could design particles
that release vaccine at injection and one month later, and mix them with
particles that release at injection and two months later, resulting in three
overall doses, each a month apart. The polymers that the researchers used in
the vaccines are already FDA-approved for use in humans, so they hope to soon
be able to test the vaccines in clinical trials.
Posted by Dr. Tim Sandle,
Pharmaceutical Microbiology