A COVID-19 vaccine strategy to give the body `border protection'
Study in animals shows a way to promote immune response in nose, mouth
and blood

Date:
August 11, 2021
Source:
Ohio State University
Summary:
A simple addition to injected COVID-19 vaccines could enhance
their effectiveness and provide 'border protection' immunity in
areas like the nose and mouth to supplement antibodies in the
bloodstream, new research suggests.



FULL STORY ==========================================================================
A simple addition to injected COVID-19 vaccines could enhance their effectiveness and provide "border protection" immunity in areas like
the nose and mouth to supplement antibodies in the bloodstream, new
research suggests.


==========================================================================
The strategy involves dampening the activity of an enzyme produced by some white blood cells when they're responding to the vaccine challenge. When
highly active, this enzyme breaks down not just the pathogen -- its job --
but also degrades pieces of cells that participate in the immune response.

Research in mice showed that an experimental COVID-19 vaccine containing
a compound to inhibit the enzyme stimulated a robust antibody response
that included immunity in the nose and mouth, ultimately providing extra protection for airways and the gastrointestinal tract.

"Our approach is to improve 'border control.' The benefits are broad
because in addition to providing protection in the bloodstream like
most vaccines do, we also have excellent protection in the doors and
windows of the body that communicate with the outside," said senior
study author Prosper Boyaka, professor and chair of the Department of Veterinary Biosciences at The Ohio State University.

"If we protect the mucosal area where the pathogen enters, then even if
you don't reach total immunity there, you limit the amount of pathogen
that enters the body so the antibodies inside are more efficient at
clearing the infection." The experimental vaccine was produced by
packaging a segment of the SARS-CoV-2 (the virus that causes COVID-19)
spike protein as an antigen with the common vaccine ingredient aluminum
salts and an enzyme inhibitor. The findings suggest this affordable
design could be particularly helpful in developing countries, where
cold storage needed for existing vaccines is a challenge, said Boyaka,
also an investigator and program director in Ohio State's Infectious
Diseases Institute.



==========================================================================
The study was published online Aug. 5 in Proceedings of the National
Academy of Sciences.

There is an irony to the use of aluminum salts (also known as alum)
in about 70% of the world's vaccines: While alum's presence actually
enhances the immune response, it also recruits the white blood cells
that secrete the enzyme, called elastase.

Alum is inexpensive to obtain or produce and can be stored at
room temperature, and is effective at promoting development of a bloodstream-based antibody response to vaccination. But it doesn't do
much for cell-mediated immunity that improves protection against viruses
and bacteria that use cells to reproduce, and can't generate a useful
number of antibodies in the body's portals of entry for most pathogens:
the nose, mouth and genitourinary tract.

The researchers found that suppressing elastase in a vaccine containing
alum had the dual benefits of broadening and speeding up the antibody
response in the bloodstream and triggering the specific types of
antibodies needed for immune protection of mucous membranes.

"We found a way to have the cells come and help the immune response
to develop and the enzyme to break down the pathogen, but we don't
want that response to be so high that it goes out of control. So we're
just putting a brake on the activity those enzymes would have," Boyaka
said. "And we found if you apply that strategy, you can induce a response
in the airways even if the vaccine is not given through the airway."
The experimental vaccine enhanced the magnitude of mouse antibodies,
which reacted to the same section of the spike protein in the vaccine
that antibodies in plasma from COVID-19 patients attach to, as well as generating antibodies in mucosal areas. Immunized mice lacking the gene
for the enzyme developed high- affinity antibodies as well.



==========================================================================
To further test the concept, the researchers found the enzyme-suppressing compound used in the study triggered production of specialized
inflammation- regulating cells in cultures of human immune cells and pig
spleen cells, showing that this strategy could improve vaccine immune
responses in other species -- including people.

Boyaka's team envisions that a future injected vaccine containing an
elastase inhibitor could expand SARS-CoV-2 vaccination availability
across the world and even be used to boost existing vaccines.

"COVID will stay with us for some time, unfortunately, with the new
variants," he said. "What we need to do is have a portfolio of options
that we could use depending on the health environment.

"Reprogramming the immune response induced by an injected vaccine
containing alum is a way to make the vaccine more efficient for what
we need. This could be a cheap and simple approach that can benefit
people in developing countries." This work was supported by grants from
the National Institutes of Health and an Ohio State Office of Research
COVID-19 seed grant. A patent application has been filed spanning this research; the overall patent portfolio includes an additional U.S. issued patent.

Co-authors, all from Ohio State, include Eunsoo Kim, Zayed Attia, Rachel Woodfint, Cong Zeng, Sun Hee Kim, Haley Steiner, Rajni Kant Shukla,
Namal Liyanage, Shristi Ghimire, Jianrong Li, Gourapura Renukaradhya,
Abhay Satoskar, Amal Amer, Shan-Lu Liu and Estelle Cormet-Boyaka.

========================================================================== Story Source: Materials provided by Ohio_State_University. Original
written by Emily Caldwell. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Eunsoo Kim, Zayed Attia, Rachel M. Woodfint, Cong Zeng, Sun Hee Kim,
Haley E. Steiner, Rajni Kant Shukla, Namal P. M. Liyanage, Shristi
Ghimire, Jianrong Li, Gourapura J. Renukaradhya, Abhay R. Satoskar,
Amal O. Amer, Shan-Lu Liu, Estelle Cormet-Boyaka, Prosper N. Boyaka.

Inhibition of elastase enhances the adjuvanticity of alum and
promotes anti-SARS-CoV-2 systemic and mucosal immunity. Proceedings
of the National Academy of Sciences, 2021; 118 (34): e2102435118
DOI: 10.1073/ pnas.2102435118 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210811131506.htm

--- up 13 weeks, 5 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)