Inhalable 'aerogel' triggers immunity to COVID-19 in mice, may block transmission

Date:
March 17, 2022
Source:
Penn State
Summary:
An inhalable 'aerogel' loaded with DNA that encodes for
the SARS-CoV- 2 spike protein successfully induces an immune
response against COVID-19 in the lungs of mice, according to new
research. The team said its aerogel could be used to create an
inhalable vaccine that blocks SARS- CoV-2 transmission by preventing
the virus from establishing an infection in the lungs.



FULL STORY ==========================================================================
An inhalable 'aerogel' loaded with DNA that encodes for the SARS-CoV-2
spike protein successfully induces an immune response against COVID-19 in
the lungs of mice, according to new research conducted at Penn State. The
team said its aerogel could be used to create an inhalable vaccine that
blocks SARS-CoV- 2 transmission by preventing the virus from establishing
an infection in the lungs.


========================================================================== "There are many potential advantages of an inhalable formulation
compared to an injectable vaccine," said Atip Lawanprasert, graduate
student in biomedical engineering and a lead author of the study, which published recently in the journal Biomacromolecules. "One is avoidance of needles. Inhalable vaccines might be able to help increase the rate of vaccination because so many people are afraid of injections. No matter
how high the efficacy of a vaccine, if people don't get it, then it's
not useful." Scott Medina, assistant professor of biomedical engineering,
Penn State, added that inhalable vaccines may be more shelf stable than traditional vaccines.

"Importantly," Medina said, "inhalable vaccines may induce an antibody
response locally in the lungs where it can potentially neutralize and
clear the virus before it fully infects the host and causes symptoms."
By contrast, Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences, explained that the injectable COVID-19 vaccines
induce a systemic immune response, which is effective at fighting
infections with SARS- CoV-2, but not as potent as an inhalable vaccine
would be in stopping the infection at the location of the virus's entry
into the body.

"The current vaccines are not very good at preventing transmission
because they allow the virus to replicate in the body, even for a short
period, and then transmit to other individuals," said Kirimanjeswara. "An inhalable vaccine would elicit local immunity at the primary site of
infection, where SARS-CoV- 2 could be rapidly neutralized and eliminated without the inflammatory response characteristic of systemic vaccination." Previously, the team had developed and patented a gel-like material,
called an 'aerogel,' as a vehicle for delivering antimicrobials to
the lungs to treat bacterial respiratory infections, particularly
tuberculosis.



========================================================================== "When the pandemic started, we decided to develop an inhalable formulation
for COVID-19 by combining our aerogel with a nucleic acid-encoded antigen
- - specifically, DNA that encodes the SARS-CoV-2 proteins," said Medina.

The researchers developed their COVID-19 formulation, which they call
CoMiP (coronavirus mimetic particle), to target alveolar macrophages --
immune cells in the respiratory tract that ingest foreign particles.

"Alveolar macrophages represent attractive targets for inhalable vaccines because they are abundant within the lungs, and previous evidence has
suggested that they may be important in early COVID-19 pathogenesis,"
said Medina.

Specifically, he explained, alveolar macrophages may be one of the first
cells to become infected by SARS-CoV-2 when the virus is inhaled.

"Alveolar macrophages are one of our key defenders against viral infection because they serve to present antigens to the rest of the immune system,"
said Medina.



==========================================================================
The scientists designed their CoMiPs to be rapidly ingested by alveolar macrophages, after which the macrophages would interpret the viral
antigen and begin to express the viral proteins encoded in the DNA.

"You are essentially tricking the macrophage into interpreting this
DNA and expressing this foreign spike protein," said Medina. "Once it
expresses the foreign protein, it shows it to the rest of the immune
system so the immune system can learn to recognize the protein in the
event of a SARS-CoV- 2 infection." In the laboratory, when the scientists incubated their CoMiPs with cells designed to mimic naive alveolar
immune cells, they found that the macrophages readily internalized the
CoMiPs. Next, they optimized the formulation of the CoMiPs to identify
the maximum safe dose in cells in vitro. They found that >80% of cells
remained viable at a dose of ?0.01 mg/mL.

To test the efficacy of the CoMiP vaccine, the team immunized mice via
an intranasal installation of the vaccine, followed by a booster dose
two weeks later. Next, they collected serum samples from the animals on
days 14 and 28 post vaccination and booster, respectively. They analyzed
these samples for systemic immune responses and found no statistically significant change in systemic antibody levels between CoMiP-treated
animals and control animals at either sampling time point.

To explore nose, throat and lung immune responses, the researchers
collected samples from immunized mice 30 days after vaccination to assess differences in the total and spike-protein specific lung mucosal IgA antibodies. They found a significant increase in the total IgA for mice vaccinated with CoMiPs, but IgA specifically targeting the SARS-CoV-2
spike protein was lower than expected for the vaccinated animals.

"On the benchtop, outside of the animal, we saw pretty good expression of
the proteins," said Medina. "And then when the CoMiPs were delivered into
the animal, we saw an increase in antibodies in the lung that may provide
some protection, but it was not to the extent that we would like. It's encouraging data, but there is more optimization to be done." The team
plans to continue to research the use of CoMiPs to protect against
COVID-19 In addition, Kirimanjeswara noted, "Transmission blocking,
inhalable vaccines can also be translated to multiple other viruses,
such as flu, so our CoMiP has the potential to be widely applicable."
Other authors on the paper include Andrew W. Simonson, postdoctoral
fellow, University of Pittsburgh; Sarah E. Sumner, graduate student
in veterinary and biomedical sciences, Penn State; McKayla J. Nicol,
graduate student in veterinary and biomedical sciences, Penn State;
and Sopida Pimcharoen, undergraduate student in biomedical engineering,
Penn State.

The Huck Institutes of the Life Sciences and Materials Research Institute
at Penn State supported this research.


========================================================================== Story Source: Materials provided by Penn_State. Original written by Sara LaJeunesse. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Atip Lawanprasert, Andrew W. Simonson, Sarah E. Sumner, McKayla
J. Nicol,
Sopida Pimcharoen, Girish S. Kirimanjeswara, Scott
H. Medina. Inhalable SARS-CoV-2 Mimetic Particles Induce Pleiotropic
Antigen Presentation.

Biomacromolecules, 2022; 23 (3): 1158 DOI:
10.1021/acs.biomac.1c01447 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220316145833.htm

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