Since January 2020, when the first sequencing of SARS-CoV-2 became public, the scientific community has worked of Covid-19 vaccines.
At the same time, some cases of anaphylaxis have been reported. Anaphylaxis has occurred in people with a history of immediate allergic reaction to any component of COVID-19 vaccines or to polyethylene glycol (PEG) or polysorbate. The PEG excipient, has been used two vaccines against COVID-19 infection:
- The Pfizer-BioNTech (Pfizer USA-BioNTech Mainz, Germany) and
- Moderna COVID-19 mRNA (Cambridge, Massachusetts, USA) vaccines. Sinovac (CoronaVac) vaccine does not contain PEG.
In this review, we were talk about viruses, Covid-19 vaccines and targets of vaccination studies.
Coronaviruses are a large family of viruses that usually cause mild to moderate upperrespiratory tract illnesses, like the common cold. However, three new coronaviruses have emerged from animal reservoirs over the past two decades to cause serious and widespread illness and death.
There are hundreds of coronaviruses, most of which circulate among such animals as pigs, camels, bats and cats. Sometimes those viruses jump to humans — called a spillover event — and can cause disease. Four of the seven known coronaviruses that sicken people cause only mild to moderate disease. Three can cause more serious, even fatal, disease. SARS coronavirus (SARS-CoV) emerged in November 2002 and caused severe acute respiratory syndrome (SARS). That virus disappeared by 2004. Middle East respiratory syndrome (MERS) is caused by the MERS coronavirus (MERS-CoV).
Transmitted from an animal reservoir in camels, MERS was identified in September 2012 and continues to cause sporadic and localized outbreaks. The third novel coronavirus to emerge in this century is called SARS-CoV-2. It causes coronavirus disease 2019 (COVID-19), which emerged from China in December 2019 and was declared a global pandemic by the World Health Organization on March 11, 2020.
The new coronavirus is a respiratory virus which spreads primarily through droplets generated when an infected person coughs or sneezes, or through droplets of saliva or discharge from the nose. The disease can be asymptomatic or symptomatic. Severe cases include pneumonia, severe respiratory failure, kidney failure, and death.
As SARS-CoV-2 is similar to the highly pathogenic SARS-CoV and MERS-CoV, experiences in the development of vaccines against other Betacoronaviruses may facilitate the COVID-19 vaccine development
Since January 2020, when the first sequencing of SARS-CoV-2 became public, the scientific community has worked toward rapid development of mRNA, protein, viral vector, and other types of Covid-19 vaccines. Two vaccine efficacy trials have been completed, and the two vaccines have recently received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA). The first vaccine given such authorization, an mRNA vaccine, BNT162b2 from Pfizer and BioNTech, showed 95% vaccine efficacy.
Today, the Journal is publishing the trial results establishing the efficacy of a second mRNA-LNP vaccine, mRNA-1273 from Moderna. Coronavirus Efficacy (COVE) trial, 30,420 volunteers were randomly assigned to receive either vaccine or placebo . Covid-19 was confirmed in 185 participants in the placebo group and 11 participants in the mRNA-1273 group, for a vaccine efficacy of 94.1%.
Both the Moderna vaccine and the Pfizer–BioNTech vaccine begin to protect recipients approximately 10 days after the first dose, with maximum protection after the second dose.
Target of Covid-19 Vaccines
Before talking about the target, we should talk about SARS-CoV-2 virus. SARS-CoV-2 contains four major structural proteins, namely spike (S), membrane (M) and envelope (E) proteins and nucleocapsid (N) protein. S proteins are responsible for recognition of the host cellular receptor to initiate virus entry. M proteins are shape the virion envelope.
E proteins are small polypeptides that are crucial for coronavirus infectivity. N proteins make up the helical nucleocapsid. In addition to these structural proteins, SARS-CoV-2 encodes 16 non-structural proteins and 9 accessory proteins. And ofcourse, several of these viral proteins could potentially serve as targets of vaccine-induced immune responses.
S protein is the main protein used as a target in COVID-19 vaccines. S protein consists of a membrane-distal S1 subunit and a membrane-proximal S2 subunit. The S1 subunit determines receptor recognition via its receptor-binding domain (RBD), whereas the S2 subunit is responsible for membrane fusion, which is required for virus entry.
In this context, vaccines are obtained in different ways. There are many ways to prepare a vaccine. All that is shown in figüre 1 below but in this study, we will only talk about the popular covid vaccine groups.
1. Traditional inactivated whole-virus vaccines: These vaccines are based on a living virus that has been killed or inactivated, not leading to a clinical disease. This technology is the most traditional.The inactivated viruses maintain their ability to replicate in vivo with mild or no symptoms. The viruses effectively stimulate the immune system and induce a strong immune response that prevents infection. Inactivated whole virus includes the entire disease-causing virion, which is inactivated physically by heat or chemically. The ensuing immune response is directed not only against the S protein, but also against many other SARS-CoV-2 antigens.
These vaccines have several advantages, including low production cost, safety, absence of genetic manipulation. The Chinese Wuhan Institute of biological products Sinopharm, the Beijing Institute of biological products Sinopharm, and the Chinese company Sinovac Biotech produce such types of vaccines.
2. mRNA-based vaccines: In the RNA (Ribonucleic Acid) vaccines or mRNA (messenger RNA) vaccines), short-lived synthetically created molecules of the RNA sequence transfected by COVID-19 virus are injected in the individual. The transfected DNA molecules enter into the immunity cells. The infected vaccine’s RNA functions as mRNA inside the immune cells of the vaccinated individual and induce the cells to produce a foreign protein that would normally be produced by a virus. These protein molecules stimulate an adaptive immune responses that can further identify and destroy the corresponding pathogen.
The lipid nanoparticles (LNPs) are the most frequently used vectors for in vivo mRNA vaccine delivery. Indeed, LNPs protect the mRNA against degradation, can be co-delivered with adjuvants, can be synthesized with relative ease in a scalable manner, can be targeted to the desired cell type by surface decoration with ligands, and facilitate endosomal escape. The Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines are examples of this kind of vaccine.
3. Adenoviral vector vaccines: In adenoviral vector vaccines, a DNA gene unique to the virus being targeted is added to the viral vector. Such viral vectors are viruses from chimpanzees, gorillas or human adenoviruses. This is done because a preexisting immunity against the virus vector may affect vaccine efficacy. The viral vector is used to shuttle this gene into a human cell. For COVID-19 vaccines, this gene codes the S protein, which is only found on the surface of SARS-CoV-2.
Once inside a cell, the viral vector uses this gene and the cell’s mechanism to produce the S protein and display it on the cell’s surface. The virus in which the DNA is inserted may lose its ability to replicate. Non-replicating vectors are used in Astra Zeneca, Sputnik V Gam-COVID-Vaccine, and Johnson & Jonhson under production vaccine.
Biontech Vaccine Causes Anaphylaxis
On the first day of the UK vaccination campaign with the coronavirus disease 2019 (COVID-19) vaccine there were reports of 2 cases of anaphylaxis within minutes of administration of the Pfizer/BioNTech messenger RNA (mRNA) vaccine and a third case of an allergic reaction . Anaphylaxis is a life-threatening allergic reaction that does occur rarely after vaccination, with onset typically within minutes to hours. This was alarming, as anaphylaxis to vaccines is rare; in the order of 1 case per million doses and therefore likely to injure public confidence.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) issued precautionary advice restricting access to the which was subsequently relaxed in line with the Summary of Product Characteristics. The cause of these vaccine anaphylaxis cases is unclear, but polyethylene glycol (PEG) is a candidate allergen. Here we demonstrate for the first time that allergy to PEG can cause anaphylaxis to the Pfizer/BioNTech vaccine.
Allergy to PEG is rare PEG is an excipient of many drugs but hypersensitivity depends on its molecular weight (MW).A fifty-two year old female developed throat constriction, cough then loss of consciousness immediately after receiving the Pfizer/BioNTech COVID19 vaccine. She had a respiratory rate of 30/min, tachycardia of 150/min and oxygen saturation of 85%.
Her blood pressure became unrecordable although central pulse remained palpable. She gave a history of allergic reactions to multiple products. She reports drug anaphylaxis many years ago. Skin prick tests were negative to all PEGs at 0.1% concentration and to the Pfizer/BioNTech vaccine, its other excipients, polysorbate 80 and the AstraZeneca COVID-19 vaccine.
Twelve minutes after skin testing, and 2 minutes after the skin test became positive, she developed a systemic reaction with widespread pruritus, urticaria and coughing with throat constriction. She was treated in clinic with intramuscular adrenaline 0.5mg, intravenous chlorphenamine 10mg and hydrocortisone 200mg. Her blood pressure improved but coughing persisted, with a drop in oxygen saturation to 85%.
A second dose of intramuscular adrenaline 0.5mg was administered and she rapidly improved. PEG allergy was diagnosed as the cause of her Pfizer/BioNTech vaccine anaphylaxis. Although the Pfizer/BioNTech vaccine contains a number of excipients, PEG 2000 is the only one reported to cause anaphylaxis.
All mRNA vaccines are likely to contain PEG which is used to stabilise the lipid nanoparticles; and the Moderna COVID-19 vaccine also contains PEG 2000 These are the first mRNA vaccines to be licensed in UK so there is no prior information on allergic reactions to mRNA vaccines. As far as we can determine, PEG has not been used as an excipient in vaccines until now.
Polysorbate 80 is an excipient in the Oxford/AstraZeneca vaccine. There has been suggestion of cross-reactivity between PEG and polysorbate 80 due to their similar chemical structures. For example, Garvey found 3 of 10 PEG-allergic patients had positive skin prick tests to polysorbate 80 at 20% . It is unclear whether this translates into clinical cross-hypersensitivity. Polysorbate 80 is used as an excipient in many drugs (including some vaccines such as influenza) and as a food additive and is thus widely tolerated.
During the same period, VAERS identified 83 cases of nonanaphylaxis allergic reaction after Pfizer-BioNTech COVID-19 vaccination with symptom onset within the 0–1-day risk window, 87% of which were classified as nonserious.
Does Sinovac Vaccine Cause Anaphylaxis?
If we talk about the sinovac vaccine (CoronaVac) , we know that two doses of CoronaVac were safe and well tolerated at doses of 1.5 μg, 3 μg, and 6 μg among adults aged 60 years and older. The incidence of adverse reactions in different dose groups was similar, indicating that there was no dose-related aggravation concern with regard to safety. Moreover, most adverse reactions are mild and transient, and injection site pain is the most reported symptom. Anaphylaxis due to a different component has not been reported.
Do Covid-19 Vaccines Cause Death?
Recently, several cases of death, after vaccination, are being announced through public sites and mass media, which bring chaos in the field and public doubts on the safety of vaccination. A fundamental problem in public health is the distrust in the national vaccine program. However, purely scientific reports on such events are lacking. No reports of deaths following COVID-19 vaccinations have been published and cited in PubMed. In the 14–23 December 2020 FDA EUA, neither deaths from anaphylaxis nor any deaths associated with COVID-19 vaccination from other etiologies were reported.
However, in Norway, 29 patients died shortly after receiving the vaccine. Physicians have been told to conduct more thorough evaluations of very frail elderly patients in line to receive the Pfizer BioNTech vaccine against COVID-19. The medical director of the Norwegian Medicines Agency speculated that common adverse reactions of mRNA vaccines, such as fever, nausea, and diarrhea, may have contributed to fatal outcomes in some of the frail patients. Some of these individuals, apparently, experienced anaphylaxis, and concerns have been raised about the cause of such allergy and anaphylaxis.
Since January 2020, when the first sequencing of SARS-CoV-2 became public, the scientific community has worked of Covid-19 vaccines. At the same time, some cases of anaphylaxis have been reported. Anaphylaxis has occurred in people with a history of immediate allergic reaction to any component of COVID-19 vaccines or to polyethylene glycol (PEG) or polysorbate. The PEG excipient, has been used two vaccines against COVID-19 infection:
(1) The Pfizer-BioNTech (Pfizer USA-BioNTech Mainz, Germany) and
(2) Moderna COVID-19 mRNA (Cambridge, Massachusetts, USA) vaccines Sinovac (CoronaVac) vaccine does not contain PEG.
Before administration of any of the currently available COVID-19 vaccines, the individual’s past medical history should be assessed for any previous severe or mild allergic reactions to any cause and especially to the vaccine’s components. The Centers for Disease Control (CDC) and the World Allergy Organization Anaphylaxis Committee have issued clear safety recommendations regarding receiving the vaccine for those with a history of allergic reactions.
The Center presented an algorithm to assist with decision-making regarding who can safely receive the COVID-19 vaccine. Individuals with common allergies to several medications, foods, inhalants, insect stings, and latex have the same chance to develop an allergic reaction to the COVID-19 vaccine. Those with a history of a severe allergic reaction due to any cause should be monitored for a 30-min observation period if vaccinated with the COVID-19 vaccine. Anyone with a history of immediate allergic reaction of any severity to any component of mRNA COVID-19 vaccines or to polyethylene glycol or polysorbate should not be vaccinated with the Pfizer-BioNTech or Moderna COVID-19 vaccine.
Patients with a history of severe allergic reactions to PEG or polysorbate should avoid the current vaccination. Patients with a history of severe allergic reactions to other vaccines or injected drugs shouldbe referred to an allergist for further investigation. Patients with a latex allergy should receive the vaccine in an absolutely latex-free environment.
The rest of the patients with a history of allergic reactions, as defined above, should receive the vaccine with a possibility of allergic reaction similar to the general population. Also, supplementation with vitamin D3 and liposomal luteolin could also be useful as they can further suppress allergic inflammation and have also been reported to be beneficial in COVID-19.
Researcher by Hatice Gül Fazlıoğlu