Israeli experts analyze mRNA COVID vaccines long-term effects

Experts believe there will be no long-term side effects to the mRNA vaccines.

Authors: By MAAYAN JAFFE-HOFFMAN   AUGUST 30, 2021 22:34

As thousands of Israelis rush back to their health funds in search of a third COVID-19 vaccine shot and a Green Pass from isolation after traveling abroad, others are asking if another injection of messenger RNA is safe.The American Food and Drug Administration provided full approval of the Pfizer coronavirus vaccine last week, but noted in its press release that “information is not yet available about potential long-term health outcomes.”However, Tal Brosh, head of the Infectious Disease Unit at Samson Assuta Ashdod University Hospital, told The Jerusalem Post that while he cannot claim to know what is going to happen in 10 years, “there is no true reason to think there are any significant long-term effects” of the vaccine.He explained that there is no other vaccine that was evaluated for a decade before approval and that there is not an example of another vaccine – although no other vaccine is an mRNA vaccine – that has been linked to any significant long-term effects.“There is no evidence of something happening unless it happened in the first two hours, two weeks or two months,” said Michal Linial, a professor of biological chemistry at the Hebrew University of Jerusalem. “We do not know of any other examples in which the immune system decided to suddenly react to a vaccine that was given 15 years prior.”THERE ARE also few examples of people being nervous about taking a booster shot of an already approved vaccine.If a person were to get cut by rusted metal and go to a doctor, the health professional would probably tell that individual to get a tetanus booster shot. It is unlikely this person would ask the doctor if the booster was safe or if it could prevent her from getting pregnant or him from making babies.“This is the same thing,” Linial said. “I can understand in the beginning that this was a breakthrough and people were shocked, like it is some kind of satellite to the Moon and they don’t want to be the first on the satellite. But now we know: This is nothing like that.”Rather, more than two billion people worldwide have been inoculated against COVID-19 with more than five billion doses. Around 210 million Pfizer mRNA doses have been distributed in America, for example. In Israel, more than 8.5 million doses have been administered. While traditional vaccines generally put a weakened or inactivated germ into our bodies, according to the Centers for Disease Control and Prevention, mRNA vaccines “teach our cells how to make a protein – or even just a piece of a protein – that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies.”Brosh said that this does not mean that the vaccine changes people’s genetic code. Rather, he said the mRNA is more like a USB device that is inserted into a computer: It does not impact the hard drive of the computer but runs a certain program.“ Messenger RNA is a very fragile molecule, meaning it can be destroyed very easily,” Linial explained. “If you put mRNA on the table, for example, in a minute there will not be any mRNA left. This is as opposed to DNA, which is as stable as you get. ”She said that this fragility is true of the mRNA of any living thing, whether it belongs to a plant, bacteria,

WHILE THE Moderna and Pfizer vaccines are based on new technologies, they are asking our bodies to do something they do every day: cells synthesizing protein. Moderna and Pfizer are simply delivering a specific mRNA sequence to our cells. Once the mRNA is in the cell, human biology takes over. Ribosomes read the code and build the protein, and the cells express the protein in the body. This is one of the main reasons to believe there will be no long-term consequences to the vaccine, said Prof. Eyal Leshem, director of Sheba Medical Center’s Center for Travel Medicine and Tropical Diseases. While the Pfizer and Moderna vaccines are the first mRNA ones to ever be brought to market for human patients, Linial said she believes the reason that no mRNA vaccine has been developed until now is because there was just no need to move this fast on a vaccine until COVID-19 came along. In fact, scientists have been experimenting with mRNA for the better part of the last three decades. Leshem said mRNA vaccines for other diseases, including cancer, have been tested in humans for around 10 years and “no long-term effects were registered” in those trials – though he admitted that these trials generally included small numbers of participants. Individuals began receiving mRNA vaccines against COVID-19 as early as July of last year, and adverse effects have been closely tracked worldwide since then. In Israel, the first vaccines were administered on December 20, 2020.“There is more data on the adverse events of these vaccines than we have ever had on any other vaccine,” Brosh said, adding that no vaccine has ever been given to so many people so quickly. Most adverse events were simple “reactogenicity” – reactions that occur soon after vaccination and that are a physical manifestation of the inflammatory response. These can include fever, muscle pain, swelling at the site of injection or swelling of the lymph nodes, for example – all symptoms that can generally be treated with paracetamol or the like. THE VACCINE was linked to one “immune-mediated phenomenon,” said Brosh, and that is myocarditis – inflammation of the heart muscle – which was the predominant serious side effect in young male adults between the ages of 16 and 25. But even then, myocarditis was rare, generally mild, and those people who developed it fully recovered, he said. Moreover, unvaccinated people who contracted COVID-19 were four times more likely to develop myocarditis than vaccinated people were, according to a new study by Clalit Health Services together with Harvard University that was published last week in the New England Journal of Medicine. The study found that there were around 2.7 cases of myocarditis per 100,000 vaccinated people infected with the virus, compared with 11 cases per 100,000 unvaccinated people who were infected. In general, the study showed that individuals who take the Pfizer coronavirus vaccine may suffer from four out of up to 25 clinically relevant side effects: myocarditis, swelling of the lymph nodes, appendicitis and herpes zoster.In contrast, high rates of multiple serious adverse events were associated with coronavirus infection among unvaccinated patients, including a greatly increased risk of developing myocarditis, pericarditis, arrhythmias, heart attacks, strokes, pulmonary embolism, deep-vein thrombosis or acute kidney damage.“So, all together we know the vaccines are safe and effective. This holds true for the initial doses and probably also for the booster doses,” Leshem said. Linial said she believes that most future vaccines will be made of mRNA because “it is an easy, great technology – no question.” She also said that vaccination is the only way to beat this pandemic. “If people want to go back to their lives,” Linial said, “the population must be vaccinated.” 

Walking down the memory lane with SARS-CoV-2 B cells

Authors: Natalia T FreundMotti GerlicBen A Croker

The end of the coronavirus disease 2019 (COVID-19) pandemic is in sight. We have scientists to thank for that. However, while years of meticulous research by vaccinologists, molecular biologists and immunologists provided the framework for rapid deployment of vaccines, we are still learning what constitutes an effective lifelong immune response to pathogens. A more detailed understanding of human B-cell development and the nature of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or immunization may aid vaccine development for known pathogens and further reduce vaccine development times in the event of future pandemics.

Neutralizing antibodies are produced upon infection with SARS-CoV-2,12 but the transition to lifelong immunity awaits ongoing studies, and is of central importance to ending COVID-19. Immunological memory is the pillar by which vaccines offer education to our immune system to protect us from future exposure to pathogens, yet the nature and length of this memory vary. Some natural infections and vaccines provide a lifelong lesson to the immune system, thereby enabling it to “remember” pathogens and antigens for decades, while in other cases the immune system “forgets” the exposure, leading to a waning immune response over months to years. With the advent of vaccines against SARS-CoV-2, along with the emergence of variants of concern, understanding the nature and duration of protective immunity is key to SARS-CoV-2 eradication or, at least, minimalization of severe infections leading to hospitalization and death.

To study long-term immunity to SARS-CoV-2 infection and vaccination, Wang et al.3 have investigated memory B-cell responses to SARS-CoV-2 for a 12-month period in convalescent individuals, some of whom received a COVID-19 messenger RNA (mRNA) vaccine. SARS-CoV-2 convalescent individuals are advised to receive one dose, and in some countries two doses, of a COVID-19 vaccine to increase titers of SARS-CoV-2 antibodies to a level considered effective at virus neutralization. This recent study enables a longitudinal comparison of the natural B-cell response with infection, with and without a supplemental COVID-19 vaccine.

For More Information: https://onlinelibrary.wiley.com/doi/10.1111/imcb.12494

Swedish Professor Says 5 Shots Of COVID Vaccine May Be Necessary

While many people have bragged about being “fully vaccinated” after taking two COVID-19 jabs, a Swedish professor says that as many as five shots may be needed to combat falling immunity.

“We don’t know how long the vaccine protects against serious illness and death,” said Karolinska Institute Professor Matti Sällberg.

“This means that you pick the safe before the unsafe.”

Numerous European countries are planning a 3rd round of COVID “booster shots” in September, and the FDA also indicated that vaccinated individuals will be given another shot in the fall.

However, Sällberg suggests this probably won’t be enough and that “recurring shots” will be necessary.

“After receiving the second dose, the immune response slowly subsides. Within a year, many may have lost their protection. We do not know yet, but if you get a third dose, it will be activated again,” he said.

“Biology says that a fading immune response is not unlikely. Then it’s time for a third, fourth, maybe fifth dose”.

For More Information: https://www.zerohedge.com/covid-19/swedish-professor-says-5-shots-covid-vaccine-may-be-necessary

Review the safety of Covid-19 mRNA vaccines: a review

Authors: Pratibha Anand 1Vincent P Stahel 2

Abstract

The novel coronavirus disease 2019 (COVID-19) has infected more than 100 million people globally within the first year of the pandemic. With a death toll surpassing 500,000 in the United States alone, containing the pandemic is predicated on achieving herd immunity on a global scale. This implies that at least 70-80 % of the population must achieve active immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either as a result of a previous COVID-19 infection or by vaccination against SARS-CoV-2. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95 % after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions. The rapid pace of vaccine development and the uncertainty of potential long-term adverse effects raised some level of hesitation against mRNA vaccines in the global community. A successful vaccination campaign is contingent on widespread access to the vaccine under appropriate storage conditions, deployment of a sufficient number of vaccinators, and the willingness of the population to be vaccinated. Thus, it is important to clarify the objective data related to vaccine safety, including known side effects and potential adverse reactions. The present review was designed to provide an update on the current state of science related to the safety and efficacy of SARS-CoV-2 mRNA vaccines.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33933145/

Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials

Authors: Musha ChenYue YuanYiguo ZhouZhaomin DengJin ZhaoFengling FengHuachun Zou & Caijun Sun 

Background

Various modalities of vaccines against coronavirus disease 2019 (COVID-19), based on different platforms and immunization procedures, have been successively approved for marketing worldwide. A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.

A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials (RCTs). Data search was performed in PubMed, Embase, Cochrane library, Scopus, Web of Science, and MedRxiv. Included articles were limited to RCTs on COVID-19 vaccines. A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization (AEFI) after vaccinating different COVID-19 vaccines. Pooled risk ratios (RR) of total AEFI for inactivated vaccine, viral-vectored vaccine, and mRNA vaccine were 1.34 [95% confidence interval (CI) 1.11–1.61, P < 0.001], 1.65 (95% CI 1.31–2.07, P < 0.001), and 2.01 (95% CI 1.78–2.26, P < 0.001), respectively. No significant differences on local and systemic AEFI were found between the first dose and second dose. In addition, people aged ≤ 55 years were at significantly higher risk of AEFI than people aged ≥ 56 years, with a pooled RR of 1.25 (95% CI 1.15–1.35, P < 0.001).

Conclusions

The safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination, with inactivated COVID-19 vaccines candidates having the lowest reported AEFI. Long-term surveillance of vaccine safety is required, especially among elderly people with underlying medical conditions.

For More Information: https://idpjournal.biomedcentral.com/articles/10.1186/s40249-021-00878-5

The Thorny Problem Of COVID-19 Vaccines And Spike Proteins

Authors: W. Glen Pyle

Almost since the beginning of the COVID-19 pandemic, a piece of the SARS-CoV2 virus called the “spike protein” has drawn interest from researchers and healthcare professionals.

New research by Yuyang Lei and colleagues published in the journal Circulation Research sheds new light on how the spike protein might play a critical role in the widespread damage caused by SARS-CoV2, and offers insight into treating the complications of COVID-19.

Vaccine skeptics have seized on the study to cast doubt on the safety of vaccines. But a review of the study’s findings shows that the concerns raised by vaccine doubters are much ado about nothing.

The Study

The vascular endothelium is an important player in the illness and death associated with COVID-19. The endothelium is a system of cells that line and protect the inside of blood vessels. SARS-CoV2 injures the endothelium leading to blood clots, heart attack, pulmonary embolism, and stroke. Despite the established link between COVID-19 and these cardiovascular complications, the mechanism by which they develop is unknown.

Researchers from Jiaotong University; the University of California, San Diego; and the Salk Institute used a pseudovirus coated with spike protein to investigate the effects of the viral protein on endothelial cells. Pseudoviruses – which were first developed over 50 years ago – contain the outer shell of the virus, but they lack the viral genes needed to reproduce.

Hamsters treated with the spike protein coated pseudovirus showed lung damage similar to that seen in humans infected with SARS-CoV2. When researchers added pseudovirus to cultured endothelial cells they found that the mitochondria inside the cells were injured. Since mitochondria are responsible for providing energy to cells, their dysfunction can cause cell death.

When isolated pulmonary arteries were exposed to the spike protein carrying pseudovirus there was some disruption in the ability of the blood vessels to dilate. The decreased ability to expand blood vessels that serve the lungs could impair the ability of the body to take up oxygen from lungs that are damaged by the virus.

The novelty of this study was the discovery that the spike protein itself causes damage, and that the pathway triggered by the spike protein could explain the widespread cardiovascular complications that develop in COVID-19 patients.

For More Information: https://www.science20.com/w_glen_pyle/the_thorny_problem_of_covid19_vaccines_and_spike_proteins-254373

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Authors: Lindsey R. Baden, M.D., Hana M. El Sahly, M.D., Brandon Essink, M.D., Karen Kotloff, M.D., Sharon Frey, M.D., Rick Novak, M.D., David Diemert, M.D., Stephen A. Spector, M.D., Nadine Rouphael, M.D., C. Buddy Creech, M.D., John McGettigan, M.D., Shishir Khetan, M.D., et al., for the COVE Study Group*

Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

For More Information: https://www.nejm.org/doi/full/10.1056/NEJMoa2035389