Could the use of an intra-nasal vaccine boost, both systemic and local immunity?
Could it address the issue of the waning immunity from mRNA vaccination?
There's a big study out and we're going to talk about it.
There's been much discussion during the COVID 19 pandemic regarding the ability of the novel mRNA
vaccines to initially very effectively reduce the burden of disease and even reduce transmission.
However, as the virus has changed, the data shows that the ability of
the vaccines to reduce transmissibility, even post vaccination has now waned significantly.
Given that preclinical studies, both SARS-CoV-2 and influenza have demonstrated
that intra-nasal vaccination decreases both viral, shedding and transmission relative
to injectable vaccines. The use of a nasal vaccine that would induce mucosal immunity
is one that researchers at Yale university have been studying.
SARS-CoV-2, being a respiratory virus is transmitted through the air
and introduced into the body through the mucosal membranes found in the respiratory tract.
By developing a vaccine that generates mucosal, immunity scientists at Yale university had been
studying the possibility that inducing an adaptive immune response at mucosal sites
can not only protect from severe disease, but also prevent infection.
If this is in fact possible, this would greatly change the trajectory of the pandemic.
To understand what scientists have discovered. We need to quickly revisit the concept of immunity.
Innate immunity is immunity that you are born with. This type of immunity is non-specific to
different pathogens and includes various enzymes, mucus membranes, your skin,
stomach acid, and a variety of immune cells that help to protect the body from infection,
interferons, and interleukin-1 are also part of the innate immune response.
Adaptive immunity is a specific response to a specific antigen.
Something that the body recognizes as a foreign invader. The challenge with
adaptive immunity is that this type of response takes time. A minimum of approximately 96 hours.
Adaptive immunity includes B cells and T cells, which are specific to the invader.
And it is this immune response that establishes immune memory
in the body. The mucosal immune response is unique in that it offers both inductive
sites where antigen specific B-cell and T-cell responses are initiated and effector sites where
the adaptive immune responses are mediated. These inductive sites vary between species
and between different mucosa. For example, the immune response in the gut mucosa is different
than immune response in the respiratory mucosa. When an antigenic foreign invader,
in this case, a virus enters the respiratory tract, it must penetrate the mucosal layer
and gain access through the epithelium.
If successful the virus travels through the next layer, the lamina propria, and from there
can be transported through blood and lymph tissues to distal sites such as other organs.
Indeed studies now show that SARS-CoV-2 has now been found in almost every tissue in the body.
Thus stopping the virus before it can enter the mucosa would be incredibly beneficial.
Importantly though, the mucosa immune responses differ in different areas of the body.
They are able to cross talk or communicate between different mucosa
and thus an immune response generated in the respiratory tract. In this case,
by a nasal vaccine would promote an immune response at distant mucosal sites in the.
body. To date, all COVID-19 vaccines are given by injection and intramuscularly.
According to head researcher, Dr. Akiko Iwasaki the immune response generated
by this type of vaccine is robust and able to generate consistent systemic T
and B cell responses. These responses are effective in inhibiting viral, spread and disease.
However, to block infection, there must be immunity at mucosal surfaces.
If you're getting value out of this video, please hit the like button and subscribe.
I appreciate your support. And it really helps me on the channel. Intra-nasal vaccines are
nothing new. The nasal vaccine that has been available in Canada for multiple
years to combat influenza has demonstrated good efficacy in preventing seasonal flu.
However, these vaccines have their challenges in order to stimulate
an effective immune response. These vaccines are classified as live vaccines.
They are unable to cause disease, but they're also unsafe in those who are immune compromised.
Inert antigens on their own do not produce an adequate immune response
and would require the use of an adjuvant, which is not safe for this type of nasal delivery.
Scientists at the Iwasaki lab tested multiple boosting agents, including a biodegradable
non-inflammatory mRNA lipid nanoparticle, as well as a purified spike protein that had been
stabilized. By using that simplified spike protein as a nasal vaccine,
after an initial intramuscular mRNA, a vaccine in mice,
both delivery methods showed evidence of a significant boost in nasal lung and serum IgA
and IgG antibodies and resident memory B cells. It should be noted that intra-nasal spike without
a dose of mRNA did not induce antibodies or T cells. Thus, the approach here is dependent on the
initial dose of mRNA, followed by an intra-nasal boost of spike protein. With this approach,
scientists observed significant CD4 tissue, resident memory and spike specific CD8 TRS.
This response was noted in every respiratory compartment and viral
load was also significantly decreased. In an attempt to mimic waning immunity,
they also compared how well this approach compares to only one dose of MRN and gave
the mice a low dose of mRNA vaccine initially followed by the intra-nasal spike protein.
42 days later, they challenged the mice with a lethal dose of
SARS-CoV-2. Thus this approach is dependent on an initial intramuscular vaccine,
followed by intra-nasal vaccine. What scientists are calling PRIME AND SPIKE. The results made
it very clear that by priming the mice with mRNA intramuscularly at a therapeutic dose,
followed by intra-nasal spike protein, all mice were protected from disease and death.
This approach also significantly reduced both nasal and lung viral load.
As lead scientist and researcher, Dr. Akiko, Iwasaki said these immune cells are waiting in
the nose like ninjas. They know what to look for because they've seen it before
the results of the study show that both the nasal spike vaccine and the
biodegradable mRNA nanoparticle they tested are effective in boosting mucosal, immunity in
hosts are initially primed with conventional mRNA.
This includes the ability to reduce actual infection and thus prevent disease. The
ability of the prime and spike approach to establish tissue, resident memory T and B
cells also shows that this approach is able to confer long lasting and cross-reactive.
memory that can be quickly re stimulated to prevent viral spread. The fact that
scientists observed that by using a heterologous spike protein,
that was not identical to the initial and intramuscular injection
shows that the cross protection generated by this approach is one that can generate
long lasting immunity and could also be quickly re stimulated to prevent spread of the virus.
Essentially the prime and spike approach is one that involves the use of a non-live vaccine
that can be safely used in the population by leveraging immunity from primary vaccination.
The result is robust immune memory in the respiratory tract, including a robust response
of T and B memory cells by stimulating the immune response in the nasal tract,
systemic immunity is also boosted offering complete protection and also inducing
cross-reactive immunity. Most recently, Xanadu bio has secured licensing from Yale for the
production of the preliminary nanoparticle delivery platform to support the project.
This type of technology could potentially have future applications for influenza,
RSV and even cystic fibrosis. The next steps for these researchers
will be clinical trials in larger animals and eventually in people.
So what should you take away from this video? Number one, this is the first time
that mRNA has actually been successfully used as an intra-nasal vaccine. Number two
is that it creates a very fast way to produce a vaccine that can be used nasally that is specific
for the particular variant that is circulating, number three is that this type of immunity
stimulates both local mucosal immunity, as well as systemic immunity and thereby reduces
transmission and infection. I hope this has been helpful. Take care and stay healthy. Bye-bye