Many viruses infect their hosts through
mucosal surfaces such as the lining of the respiratory tract.
MIT researchers have now developed a vaccination strategy that can create an army of T cells
that are ready and waiting at those surfaces, offering a quicker response to viral invaders.
The researchers showed that they could induce a strong memory T cell response in the lungs of mice
by giving them a vaccine modified to bind to a protein naturally present in
mucus. This can help ferry the vaccine across mucosal barriers, such as the lining of the lungs.
In addition to protecting against pathogens that infect the lungs,
these types of inhaled vaccines could also be used to treat cancer metastasizing to the lungs
or even prevent cancer from developing in the first place.
Most vaccines are given as an injection into the muscle tissue. However, most viral infections
occur at mucosal surfaces such as the lungs and upper respiratory tract, reproductive tract,
or gastrointestinal tract. Creating a strong line of defense at those sites
could help the body fend off infection more effectively.
There is an approved nasal vaccine for the flu, and an oral vaccine for typhoid, but both of those
vaccines consist of live, attenuated viruses, which are better able to cross mucosal barriers.
The MIT researchers wanted to pursue an alternative: peptide vaccines, which have a better
safety profile and are easier to manufacture, but are more difficult to get across mucosal barriers.
To try to make peptide vaccines easier to deliver to the lungs, the researchers turned
to an approach they first explored in a 2014 study. In that paper, the researchers found that
attaching peptide vaccines to albumin proteins, found in the bloodstream, helped the peptides to
accumulate in the lymph nodes, where they could activate a strong T cell response.
Those vaccines were given by injection, like most traditional vaccines.
In their new study, the researchers investigated whether albumin could
also help peptide vaccines get across mucosal barriers such as those surrounding the lungs.
One of albumin’s functions is to help maintain osmotic pressure in the lungs,
and it can easily pass through the epithelial tissue surrounding the lungs.
To test this idea, the researchers attached an albumin-binding lipid tail to a peptide
vaccine against the vaccinia virus. The vaccine also included a commonly used adjuvant called CpG,
which helps to provoke a stronger immune response.
The vaccine was delivered intratracheally, which simulates inhalation exposure.
The researchers found that this type of delivery generated a 25-fold increase in memory T cells
in the mouse lungs, compared to injecting the albumin-modified vaccine into a muscle site
far from the lungs. They also showed that when mice were exposed to the vaccinia virus
months later, the intramuscular vaccine offered no protection,
while all of the animals that received the vaccine intratracheally were protected.
The researchers also tested a mucosal vaccine against cancer. In that case,
they used a peptide found on melanoma cells to immunize mice. When the vaccinated mice
were exposed to metastatic melanoma cells, T cells in the lungs were able to eliminate them.
The researchers also showed that the vaccine could help to shrink existing lung tumors.
This kind of local response could make it possible to develop vaccines that would
prevent tumors from forming in specific organs, by targeting antigens commonly found on tumor cells.
This strategy could also be useful for creating mucosal vaccines against
other viruses such as HIV, influenza, or SAR-CoV-2.