Thursday, April 29

There could be a problem with mRNA Covid vaccines

From an April 22 article published at Medical Life Sciences  that's headlined, Striking difference identified between mRNA vaccination vs. SARS-CoV-2 infection immune responses:

A team of scientists from the United States has recently compared the immune response elicited by natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Their findings reveal that, unlike vaccination, natural SARS-CoV-2 infection is associated with a robust interferon response together with an induction of cytotoxic gene expression in peripheral blood lymphocytes. The study is currently available on the medRxiv* preprint server.

The article is directed at scientists specializing in the areas of research under discussion and therefore much of it is incomprehensible to this lay reader. Furthermore, the study is not yet peer reviewed and therefore can't be considered conclusive.  But this part of the article is reasonably understandable:

By specifically analyzing the B cell clonal expansion, the scientists indicated that the increased interferon response during SARS-CoV-2 infection might have induced the differentiation of plasma cells in COVID-19 patients. In contrast, the vaccine seemed to trigger the expansion of circulating memory B cells.

Furthermore, they observed enrichment of activated T cells and natural killer cells with a high level of cytotoxic effector functions in COVID-19 patients. However, they could not detect such an immune signature in vaccinated individuals.

The significance?

The study findings identify a notable difference between the immune responses induced by natural SARS-CoV-2 infection and vaccination. While the vaccine-induced immune response is mainly associated with viral clearance and protective immunity, an immune reaction to SARS-CoV-2 significantly increases the risk of heightened inflammation and immunopathology.

The findings square with the claim by Covid vaccine developers that their vaccines, while not necessarily giving full immunity to the Covid virus, can be very effective at protecting against the worst symptoms of the disease. I think the implication of the claim is that the vaccines ward off the infamous "cytokine storm," which is actually the killer in many if not most Covid cases. 

If I understand the study's significance correctly, I have a question:  Could the vaccines, by bypassing the immune system's response to the virus, weaken the immune system's natural defenses if the vaccines are repeatedly administered, as with annual booster shots?

I assume that would be a very hard question for scientists to answer off the top of their heads. And testing for side effects of vaccines probably wouldn't be broad enough to suggest an answer.  

However, there is a way to come at the question without  spending years at a lab bench. That would be to ask if there are ways other than the mRNA vaccine to tamp down the Covid-related cytokine storms, but which don't bypass or supplant any of the immune system's defenses. Some scientists are already asking pretty much the same question. 

Take a look at this April 13 report from The Jerusalem Post:

Can a cup of yogurt 'cure' your case of COVID-19?

Pre-clinical research by Israeli scientists, published in Microbiome, indicates that Kefir could be used to treat cytokine storms caused by coronavirus.

Can a cup of probiotic yogurt help save the lives of people with COVID-19?

Researchers from Ben-Gurion University of the Negev say they have identified molecules in kefir that are effective at treating various inflammatory conditions, including “cytokine storms” caused by COVID-19.

Kefir, which is similar to yogurt but thinner in consistency, is a fermented drink made by inoculating cow’s or goat’s milk with microorganism mixtures, such as yeast and bacteria. A cytokine storm is when the body’s immune system goes into overdrive and attacks itself – one of the leading causes of death in COVID-19 patients.

The research was conducted by PhD student Orit Malka and Prof. Raz Jelinek, vice president and dean for research and development at BGU. It was recently published in the peer-reviewed journal Microbiome.

Several years before the coronavirus pandemic, Malka noticed that yogurt had a therapeutic effect and began studying it in Jelinek’s lab, Jelinek told The Jerusalem Post. They identified molecules in the yogurt that had dramatic antibacterial and anti-inflammatory properties.

“One of the main reasons people die of COVID is the cytokine storm,” Jelinek said. “Cytokines are immune molecules that are designed to help the body fight invaders like viruses. But in certain circumstances, and scientists don’t know exactly why, the body goes into a sort of overdrive and secretes many cytokines – so many that it kills you. That is what happens during COVID.”

“We knew that we had found these molecules in yogurt with anti-inflammatory properties,” he said. “So, when COVID started, we said, Let’s see if these molecules can help against cytokine storms.”

Jelinek and Malka induced cytokine storms in mice. Then they watched what happened.

The mice that had the storm and were not treated died. But the mice that were treated with the molecules they found in the yogurt had a complete recovery. The molecules not only eliminated the cytokine storm, they also restored balance to the immune system.

“This was really remarkable,” Jelinek said.

The scientists said they also administered the molecules to the mice via their mouths; they were placed in water and entered the mice’s digestive systems just like a normal drink.

During the pandemic, Jelinek and Malka had hoped they could administer these molecules to patients who were in critical condition. But regulatory hurdles delayed the process, and they did not succeed, Jelinek said. Now, their next step is to conduct clinical trials with other cytokine storms.

“Cytokine storms don’t only happen with COVID,” Jelinek said. “This is a very bad condition with really very few treatments against it.”

The researchers are about to make a start-up company under the BGN Technologies umbrella for further development and commercialization of the technology. The company should formally be launched within the next few weeks, and then they will raise funds to conduct clinical experiments, Jelinek said. Hopefully, trials will begin within a few months, he said.

Prof. Eran Segal, a computational biologist for the Weizmann Institute of Science who has published extensively on the subject of probiotics, said that "I am a strong believer in the concept of probiotics when given for the right indications and after proper research and showing some benefits."

On the other hand, he said, "a lot of probiotics that are given, don't do anything."

"The potential is huge," he added. "I think it is still in the early days."

The path from the lab to the table is likely to be long, Jelinek admitted. Even though the molecules come from yogurt that people could eat every day, they would be considered a drug and will have to undergo the full scrutiny of any new medicine before receiving approval, Jelinek said.

As such, the company will likely take the molecules in another direction at the same time – as a food additive, probiotic or supplement – to speed up the approval process, he said.

Jelinek said he and Malka did other experiments with the kefir, and they were also able to demonstrate that the molecules have the potential to combat pathogenic bacteria. Specifically, they showed that the molecules were able to significantly reduce virulence of the causative agent of cholera, he said.

“This is the first demonstration that virulence of human pathogenic bacteria can be mitigated by molecules secreted in probiotic milk products, such as yogurt or kefir,” Jelinek said. “I don’t think there were any molecular mechanisms that people knew for sure would have a therapeutic effect. Now we know.”



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