Materiały źródłowe

• #1

  https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html

  Moderna, a Massachusetts-based vaccine developer, partnered with the National Institutes of Health to develop and test a coronavirus vaccine known as mRNA-1273. A clinical trial demonstrated that the vaccine has an efficacy rate of more than 90 percent in preventing Covid-19. […] Like the Pfizer-BioNTech vaccine, Modernas vaccine is based on the viruss genetic instructions for building the spike protein. […] The vaccine uses messenger RNA, genetic material that our cells read to make proteins. […] After injection, the vaccine particles bump into cells and fuse to them, releasing mRNA. The cells molecules read its sequence and build spike proteins. […] Some of the spike proteins form spikes that migrate to the surface of the cell and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.

• #2 About Sputnik V | Official website vaccine against COVID-19 Sputnik V.

  https://sputnikvaccine.com/about-vaccine/

  In order to ensure lasting immunity Russian scientists came up with a breakthrough idea to use two different types of adenovirus vectors (rAd26 and rAd5) for the first and second vaccination, boosting the effect of the vaccine. […] Efficacy of Sputnik V against COVID-19 was reported at 91.6%. The figure is based on the analysis of data on 19,866 volunteers, who received both the first and second doses of the Sputnik V vaccine or placebo at the final control point of 78 confirmed COVID-19 cases. Sputnik Vs efficacy was validated by internationally peer reviewed data published in The Lancet. […] The vaccine produces protective neutralising antibody titres against new strains including Alpha B.1.1.7 (first identified in the UK), Beta B.1.351 (first identified in South Africa), Gamma P.1 (first identified in Brazil), Delta B.1.617.2 and B.1.617.3 (first identified in India) and variants B.1.1.141 and B.1.1.317 with mutations in the receptor-binding domain (RBD) identified in Moscow.

• #3 Immunological mechanisms of vaccine-induced protection against COVID-19 in humans | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00578-z

  Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. […] These data suggest that protection may require low levels of NAbs and might involve other immune effector mechanisms including non-NAbs, T cells and innate immune mechanisms. Identifying the mechanisms of protection as well as correlates of protection is crucially important to inform further vaccine development and guide the use of licensed COVID-19 vaccines worldwide. […] Non-NAbs can also have an important role in protection, however, via Fc-mediated effector functions including antibody-dependent phagocytosis, antibody-dependent cellular cytotoxicity and antibody-dependent natural killer cell activation. […] Evidence from human and animal studies has suggested that in addition or, possibly, instead of high titres of NAbs a robust cytotoxic CD8+ T cell response and a TH1 cell-biased CD4+ T cell effector response would result in protective immunity against COVID-19.

• #4 Immunological mechanisms of vaccine-induced protection against COVID-19 in humans | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00578-z

  Like other pathogenic respiratory RNA viruses (including other coronaviruses, respiratory syncytial virus and enteroviruses), SARS-CoV-2 can evade innate immune responses via multiple mechanisms, indicating that innate immunity is likely crucial for host protection. […] The timing of induction of type I interferon (or type III interferon in mucosal tissue) is crucial as the presence of type I interferon early in infection appears to be protective, whereas its relevance for viral control at later time points may be reduced or may even contribute to immunopathology. […] Most candidate COVID-19 vaccines are designed to elicit immune responses, ideally mediated by neutralizing antibodies (NAbs), against the trimeric SARS-CoV-2 spike (S) protein. […] Eliciting an immune response that targets the RBD has been a major focus of vaccine development on the assumption that antibodies that bind this critical domain can prevent viral entry into host cells, thereby allowing for sterilizing immunity.

• #5 COVID-19: Mechanisms of Vaccination and Immunity

  https://www.mdpi.com/2076-393X/8/3/404

  The primary immune mechanism of avoiding infection is through blocking viral attachment to ACE2. Therefore, generating a vaccine inducing antibodies against RBD is the strategy used by the majority of COVID-19 vaccine candidates. […] Antibody-mediated enhanced disease may be caused by two different mechanisms. The first is called antibody-dependent enhancement (ADE) of infection, which occurs when antibodies promote viral uptake via Fcγ receptors, thereby increasing viral infection and pathogenicity. […] Together, these data suggest that efficient and safe strategies of vaccination may be achieved by the preferential usage of antigens that display neutralizing epitopes and the relative avoidance of other epitopes to limit the risk through disease enhancing antibodies. […] A major hurdle is the very limited pre-existing clinical experience with any coronavirus vaccine, increasing the failure risk of COVID-19 vaccine trials and consequent delay. […] We suggest that COVID-19 vaccines are promising when they induce large quantities of high affinity neutralizing antibodies and only relatively low amounts of other antibodies and immune responses bearing the risk of disease enhancement.

• #6 What are mRNA vaccines and how do they work?: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/understanding/therapy/mrnavaccines/

  Vaccines help prevent infection by preparing the body to fight foreign invaders (such as bacteria, viruses, or other pathogens). All vaccines introduce into the body a harmless piece of a particular bacteria or virus, triggering an immune response. Most vaccines contain a weakened or dead bacteria or virus. However, scientists have developed a new type of vaccine that uses a molecule called messenger RNA (mRNA) rather than part of an actual bacteria or virus. Messenger RNA is a type of RNA that is necessary for protein production. Once cells finish making a protein, they quickly break down the mRNA. mRNA from vaccines does not enter the nucleus and does not alter DNA. […] mRNA vaccines work by introducing a piece of mRNA that corresponds to a viral protein, usually a small piece of a protein found on the virus’s outer membrane. (Individuals who get an mRNA vaccine are not exposed to the virus, nor can they become infected with the virus by the vaccine.) By using this mRNA, cells can produce the viral protein. As part of a normal immune response, the immune system recognizes that the protein is foreign and produces specialized proteins called antibodies. Antibodies help protect the body against infection by recognizing individual viruses or other pathogens, attaching to them, and marking the pathogens for destruction. Once produced, antibodies remain in the body, even after the body has rid itself of the pathogen, so that the immune system can quickly respond if exposed again. If a person is exposed to a virus after receiving mRNA vaccination for it, antibodies can quickly recognize it, attach to it, and mark it for destruction before it can cause serious illness.

• #7

  https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html

  Moderna, a Massachusetts-based vaccine developer, partnered with the National Institutes of Health to develop and test a coronavirus vaccine known as mRNA-1273. A clinical trial demonstrated that the vaccine has an efficacy rate of more than 90 percent in preventing Covid-19. […] Like the Pfizer-BioNTech vaccine, Modernas vaccine is based on the viruss genetic instructions for building the spike protein. […] The vaccine uses messenger RNA, genetic material that our cells read to make proteins. […] After injection, the vaccine particles bump into cells and fuse to them, releasing mRNA. The cells molecules read its sequence and build spike proteins. […] Some of the spike proteins form spikes that migrate to the surface of the cell and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.

• #8 COVID-19 Vaccine Basics | COVID-19 | CDC

  https://www.cdc.gov/covid/vaccines/how-they-work.html

  COVID-19 vaccines help our bodies develop immunity to the virus that causes COVID-19 without us having to get the illness. […] Different types of vaccines work in different ways to offer protection. But with all types of vaccines, the body is left with a supply of memory T-lymphocytes as well as B-lymphocytes that will remember how to fight that virus in the future. […] COVID-19 vaccines do not affect or interact with our DNA. […] These vaccines do not enter the nucleus of the cell where our DNA (genetic material) is located, so they cannot change or influence our genes. […] To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein or even just a piece of a protein that triggers an immune response inside our bodies.

• #9 Understanding COVID-19 mRNA Vaccines

  https://www.genome.gov/about-genomics/fact-sheets/Understanding-COVID-19-mRNA-Vaccines

  mRNA vaccines inject cells with instructions to generate a protein that is normally found on the surface of SARS-CoV-2, the virus that causes COVID-19. […] By injecting cells with a synthetic mRNA that encodes a viral spike protein, an mRNA vaccine can direct human cells to make a viral spike protein and evoke an immune response without a person ever having been exposed to the viral material. […] These viral spike proteins, or antigens, normally coat the surface of the virus and are recognized by antibodies and other immune cells that prepare and protect the body against the virus. […] Traditional vaccines work by giving a person either viral proteins or an inactivated or weakened version of a virus that triggers an immune response. mRNA vaccines do not contain viral material. […] No. There is no risk of an mRNA vaccine changing your DNA because mRNA does not have the ability to alter DNA. […] Yes. The FDA approval process involves careful review of clinical trial data to independently confirm that a vaccine is safe and effective. […] One of the most exciting aspects of mRNA technology is how rapidly it can be developed to target a particular virus.

• #10

  https://link.springer.com/article/10.1007/s13181-023-00931-9

  mRNA vaccines are not infectious and carry no risk of insertional mutagenesis. […] The Pfizer-BioNTech and Moderna vaccines have been associated with myocarditis and anaphylaxis. […] The Johnson Johnson vaccine has been associated with thrombosis with thrombocytopenia syndrome (TTS) and Guillain-Barr syndrome (GBS). […] The adverse effects from vaccines against COVID-19 resemble those from previous vaccines in type and frequency, including a slight increase in the risk of myocarditis for young males.

• #11 Immunogenicity mechanism of mRNA vaccines and their limitations in promoting adaptive protection against SARS-CoV-2 [PeerJ]

  https://peerj.com/articles/13083/

  mRNA vaccines have emerged as promising alternatives to conventional vaccines due to their high potency with the capacity for rapid development and low manufacturing costs. […] mRNA vaccines have been shown to induce a robust CD8+T cell response, with a balanced CD4+ TH1/TH2 response. […] High levels of spike-specific IgG and neutralizing antibodies were detected after two-dose vaccination. […] The immunostimulatory capability of mRNA as well as its stability and translatability are the main critical concerns to be optimized in the mRNA vaccine development. […] The addition of 5 Cap structure by using various versions of synthetic cap analogues is crucial for efficient protein translation. […] mRNA vaccines require an efficient delivery for their success and clinical translation in the cytoplasm.

• #12 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250403/Key-cellular-mechanism-affecting-the-function-of-mRNA-vaccines-revealed.aspx

  A team of researchers led by Dr. Kim V. Narry, director of the Center for RNA Research at the Institute for Basic Science (IBS), has uncovered a key cellular mechanism that affects the function of mRNA vaccines and therapeutics. Their study, recently published in Science, provides the first comprehensive understanding of how mRNA vaccines are delivered, processed, and degraded within cells-a breakthrough that could pave the way for more effective vaccines and RNA-based treatments. […] Messenger RNA (mRNA) is the genetic blueprint that tells cells how to produce proteins. It plays a vital role in mRNA vaccines, such as those used for COVID-19, and is also a promising tool for treating diseases like cancer and genetic disorders. […] A key finding of the study was that mRNA molecules containing a special modification called N1-methylpseudouridine (m1)-which was awarded the 2023 Nobel Prize in Physiology or Medicine-can evade TRIM25 detection. This modification prevents TRIM25 from binding to mRNA, enhancing the stability and effectiveness of mRNA vaccines. This discovery not only explains how mRNA vaccines evade cellular surveillance mechanisms but also emphasizes the importance of this modification in enhancing the therapeutic potential of mRNA-based treatments.

• #13 There are four types of COVID-19 vaccines: here’s how they workverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverifiedverified

  https://www.gavi.org/vaccineswork/there-are-four-types-covid-19-vaccines-heres-how-they-work

  Viral vector vaccines also work by giving cells genetic instructions to produce antigens. But they differ from nucleic acid vaccines in that they use a harmless virus, different from the one the vaccine is targeting, to deliver these instructions into the cell. One type of virus that has often been used as a vector is adenovirus, which causes the common cold. As with nucleic acid vaccines, our own cellular machinery is hijacked to produce the antigen from those instructions, in order to trigger an immune response. Viral vector vaccines can mimic natural viral infection and should therefore trigger a strong immune response. However, since there is a chance that many people may have already been exposed to the viruses being used as vectors, some may be immune to it, making the vaccine less effective.

• #14 How the Johnson & Johnson COVID-19 vaccine works | Nebraska Medicine Omaha, NE

  https://www.nebraskamed.com/COVID/how-the-johnson-johnson-covid-19-vaccine-works

  The Johnson Johnson vaccine delivers the virus’ DNA to your cells to make the spike protein. An adenovirus acts as a delivery vehicle used to carry the coronavirus genetic material (DNA). The adenovirus delivers the little piece of DNA to the cell that will then make the spike protein. After your cells produce the spike protein, your immune system creates antibodies toward the spike protein, protecting you from infection. […] The Johnson Johnson vaccine is not an mRNA vaccine (like Pfizer and Moderna). All three vaccines deliver genetic material to your cells: mRNA vaccines deliver mRNA, and Johnson Johnson delivers DNA. Another difference is the delivery method used either a little enclosure made of fat surrounds the genetic material, or in the case of Johnson Johnson, an adenovirus carries it. But the end result is the same: both the mRNA vaccines and the Johnson Johnson vaccine help your body to develop antibodies against the coronavirus spike protein.

• #15 The Johnson & Johnson adenovirus vaccine explained

  https://www.mayoclinic.org/johnson-johnson-adenovirus-vaccine-explained/vid-20510091

  Adenovirus vaccines are not really new. Adenoviruses are really, really common and they’re really ubiquitous viruses, and they tend to cause things like the common cold, pink eye, so really common but more minor infections. […] An adenovirus vaccine is a virus that has been altered so that it can’t make you sick, it can’t replicate, it cannot integrate into your DNA, so they take out some really important parts of that virus genome. […] What’s done to the virus is that actually a little genetic snippet is exchanged and placed into the adenovirus that is actually from the COVID virus. It’s the section of genetic code that codes for the spike protein. The adenovirus is like a Trojan horse, except that what it’s delivering is a good thing, instead of delivering something that you don’t want in your body. You get the vaccine, the adenovirus goes into your cell, it’s got this Trojan horse code on it that makes the spike protein. That spike protein then goes to the surface of your cell and then your immune system recognizes it and starts to make antibodies to it.

• #16

  https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html

  The Oxford-AstraZeneca vaccine is based on the virus’s genetic instructions for building the spike protein. […] The adenovirus pushes its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger

• #17 Moths and tree bark: How the Novavax vaccine works | Nebraska Medicine Omaha, NE

  https://www.nebraskamed.com/COVID/moths-and-tree-bark-how-the-novavax-vaccine-works

  A fourth COVID-19 vaccine has been authorized in the United States. Called Novavax, it’s a more traditional vaccine that uses moth cells and tree bark. Instead of an mRNA vaccine (Pfizer, Moderna) or a viral vector vaccine (Johnson Johnson), Novavax is a subunit protein vaccine. […] The Novavax COVID-19 vaccine contains a protein (made using moth cells) plus an adjuvant (made from tree bark). An adjuvant is an ingredient added to boost a person’s immune response, creating higher levels of antibodies. […] The Novavax vaccine uses a telltale piece of the coronavirus: the notorious spike protein. All alone, the spike protein is harmless and can’t cause COVID-19. When your immune system encounters the lonely spike protein, it produces antibodies against it. This gives you protection against future COVID-19 infection.

• #18 Different types of COVID-19 vaccines: How they work

  https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465

  Subunit vaccines include only the parts of a virus that best stimulate the immune system. This type of COVID-19 vaccine has harmless S proteins in it. Once the immune system recognizes the S proteins, it creates antibodies and defensive white blood cells. If infection with the COVID-19 virus happens later, the antibodies help clear out the virus.

• #19 Moths and tree bark: How the Novavax vaccine works | Nebraska Medicine Omaha, NE

  https://www.nebraskamed.com/COVID/moths-and-tree-bark-how-the-novavax-vaccine-works

  „Unlike mRNA vaccines, the spike protein is already premade in the Novavax vaccine. It’s a shortcut,” explains Dr. Florescu. „All the synthesis happens outside the body and we just give the end product: the spike protein.” […] Like other COVID-19 vaccines, Novavax does not cause COVID-19 infection. It can’t get you sick. This vaccine doesn’t contain either live or inactivated virus. […] „The Novavax vaccine has no genetic material, only proteins,” says Dr. Florescu. „The vaccine technology is more traditional, and it’s very similar to a protein-based influenza vaccine.” […] Adjuvants increase the immune response to a vaccine. In this vaccine, soapbark tree extract adjuvant makes achieving immunity possible with a smaller dose of the spike protein. […] Using the Matrix-M adjuvant, a smaller dose of spike protein achieves the desired immune response.

• #20 Recombinant Nanoparticle Vaccine Technology | Novavax

  https://www.novavax.com/what-we-do/recombinant-protein-based-nanoparticle-vaccine-technology

  COVID-19 is caused by the SARS-CoV-2 virus. The virus uses a protein on its surface, known as the spike protein, to attach itself to human cells and cause infection. Novavax makes a protein that mimics the virus version of the spike protein. In our vaccine, we organize spike proteins into a nanoparticle to help the immune system recognize the target spike. Learning to recognize the spike proteins in this way helps the immune system protect you from getting sick from COVID-19. […] On their own, the vaccines spike protein nanoparticles are not enough to trigger a full immune response, so we mix them with our proprietary Matrix-M adjuvant to help produce a stronger immune signal with the aim of creating immunity.

• #21 Novavax’s COVID-19 Vaccine: Your Questions Answered > News > Yale Medicine

  https://www.yalemedicine.org/news/novavax-covid-vaccine

  The Novavax vaccine is one of three vaccines available in the U.S. for the prevention of COVID-19 and the only one that does not use the relatively new mRNA vaccine technology. Its unique among the available coronavirus vaccines here in that it uses a traditional virus-blocking technology thats been used against other diseases. […] Though COVID vaccines may utilize different delivery mechanisms, the end result is the same: cells in the body recognize that a spike protein (the spikes you see sticking out of the coronavirus in pictures) doesnt belong, and the immune system reacts by activating immune cells and producing antibodies to attack the real virus if you get exposed. […] But, unlike the other vaccines, Novavax directly injects a version of the spike protein, along with another ingredient that also stimulates the immune system, into the body, leading to the production of antibodies and T-cells. (It injects a version of the spike protein that has been formulated in a laboratory as a nanoparticulate that does not have genetic material inside and cannot cause disease.)

• #22 COVID-19: Mechanisms of Vaccination and Immunity

  https://www.mdpi.com/2076-393X/8/3/404

  Here, we review the mechanistic understanding of immunity and vaccination against SARS-CoV-2. […] Vaccine development has started at a strongly accelerated pace already, shortly after the beginning of the SARS-CoV-2 outbreak. […] The knowledge gained through previous coronavirus outbreaks provides a favorable scientific basis for vaccine design— for example, by helping to identify potentially protective epitopes, the Achilles heels of a virus. […] Vaccines can be based on whole viruses (live-attenuated or inactivated), viral vectors, nanoparticles or virus-like particles, subunit components, proteins/peptides, RNA, DNA or live cells. […] Protection induced by currently available vaccines against viruses is primarily based on virus-neutralizing antibodies. Such antibodies usually block the interaction of the virus with its cellular receptor or prevent conformational changes required for fusion of the virus with the cell membrane.

• #23 COVID-19: Mechanisms of Vaccination and Immunity

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7564472/

  Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. […] The immune response to the SARS-CoV-2 involves innate immune activation and antigen-specific responses of B and T cells. Protection from viral infection is mainly achieved by virus-neutralizing antibodies, a principle that applies to the vast majority of viral infections to which humans acquire robust immune protection due to infection or vaccination. It is urgent to develop vaccines aiming at the induction of protective immune responses, primarily through virus-neutralizing antibodies specific for SARS-CoV-2.

• #24 Immunological mechanisms of vaccine-induced protection against COVID-19 in humans | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00578-z

  Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. […] These data suggest that protection may require low levels of NAbs and might involve other immune effector mechanisms including non-NAbs, T cells and innate immune mechanisms. Identifying the mechanisms of protection as well as correlates of protection is crucially important to inform further vaccine development and guide the use of licensed COVID-19 vaccines worldwide. […] Non-NAbs can also have an important role in protection, however, via Fc-mediated effector functions including antibody-dependent phagocytosis, antibody-dependent cellular cytotoxicity and antibody-dependent natural killer cell activation. […] Evidence from human and animal studies has suggested that in addition or, possibly, instead of high titres of NAbs a robust cytotoxic CD8+ T cell response and a TH1 cell-biased CD4+ T cell effector response would result in protective immunity against COVID-19.

• #25

  https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html

  The cell presents fragments of the spike protein on its surface. When other cells called helper T cells detect these fragments, the helper T cells can raise the alarm and help marshal other immune cells to fight the infection. […] Other immune cells, called B cells, may bump into the coronavirus spikes on the surface of vaccinated cells, or free-floating spike protein fragments. A few of the B cells may be able to lock onto the spike proteins. If these B cells are then activated by helper T cells, they will start to proliferate and pour out antibodies that target the spike protein. […] The antibodies can latch onto coronavirus spikes, mark the virus for destruction and prevent infection by blocking the spikes from attaching to other cells. […] The antigen-presenting cells can also activate another type of immune cell called a killer T cell to seek out and destroy any coronavirus-infected cells that display the spike protein fragments on their surfaces. […] Modernas vaccine requires two injections, given 28

• #26 2 Immunologic Response to COVID-19 Vaccines | Evidence Review of the Adverse Effects of COVID-19 Vaccination and Intramuscular Vaccine Administration | The National Academies Press

  https://nap.nationalacademies.org/read/27746/chapter/4

  Vaccines contain (subunit vaccines, such as NVX-CoV2373) or generate production of (mRNA and AV vaccines) the spike protein to elicit an immune response in the absence of infection. […] The goal of all vaccine platforms is to contain or produce a stable form of the S protein that will not degrade or be cleared from the body without activating the immune response. […] The choice of the full-length spike protein or smaller RBD of the spike protein in vaccine design balances the benefits of eliciting a broader immune response with the full-length protein versus focusing on the highly neutralizing epitopes in the RBD. […] The immunogenicity of COVID-19 vaccines largely hinges on the adaptive immune system recognizing the specific spike protein fragments. […] The rapid and effective response to a pathogen upon re-exposure is primarily mediated by memory B and T cells. […] The duration of immunity conferred by COVID-19 vaccines and the potential need for booster doses are areas of ongoing research. […] Understanding these mechanisms is paramount in ensuring the safety and well-being of individuals receiving COVID-19 vaccines.

• #27 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20220914/Mechanism-of-action-of-different-COVID-19-vaccines.aspx

  In particular, rAdVV vaccines negatively regulated the activation of the cluster of differentiation four positive (CD4+) T lymphocytes, leukocyte chemotaxis, interleukin 18 (IL-18) signaling, and monocyte mediated-antigen presentation. On the contrary, mRNA vaccines positively regulated the activation of natural killer T (NKT) lymphocytes, chemokine-mediated immune pathways, and platelet activation. […] Overall, the study findings showed that SARS-CoV-2 vaccinations induce robust but divergent immunological responses at the cellular, protein, and RNA levels.

• #28 Immunological mechanisms of vaccine-induced protection against COVID-19 in humans | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00578-z

  Like other pathogenic respiratory RNA viruses (including other coronaviruses, respiratory syncytial virus and enteroviruses), SARS-CoV-2 can evade innate immune responses via multiple mechanisms, indicating that innate immunity is likely crucial for host protection. […] The timing of induction of type I interferon (or type III interferon in mucosal tissue) is crucial as the presence of type I interferon early in infection appears to be protective, whereas its relevance for viral control at later time points may be reduced or may even contribute to immunopathology. […] Most candidate COVID-19 vaccines are designed to elicit immune responses, ideally mediated by neutralizing antibodies (NAbs), against the trimeric SARS-CoV-2 spike (S) protein. […] Eliciting an immune response that targets the RBD has been a major focus of vaccine development on the assumption that antibodies that bind this critical domain can prevent viral entry into host cells, thereby allowing for sterilizing immunity.

• #29

  https://link.springer.com/article/10.1007/s13181-023-00931-9

  SARS-CoV-2 emerged in December 2019 and led to the COVID-19 pandemic. […] Vaccines prevent progression for a larger part of the population. DNA and mRNA vaccines are more effective than protein or inactivated virus vaccines. […] After mRNA vaccines, young men are more likely to have myocarditis in the subsequent 7 days. […] The S protein is an attractive target because it elicits an immune response and mutations in it may explain the variation in virulence across SARS-CoV-2 strains. […] Understanding the structure is important for understanding the toxicity of monoclonal antibodies that bind to specific parts of the S protein, which creates the potential for each monoclonal antibody to have unique off-target effects. […] The S protein is glycosylated, which helps it evade detection by the immune system and tightly bind to ACE2 receptors.

• #30 CMR Manifestations, Influencing Factors and Molecular Mechanism of Myocarditis Induced by COVID-19 Mrna Vaccine

  https://www.imrpress.com/journal/rcm/23/10/10.31083/j.rcm2310339

  Although immunization with the 2019 coronavirus disease (COVID-19) mRNA vaccine is considered to be an effective measure to reduce the number of serious cases or deaths associated with COVID-19, rare cases of cardiac complications have been reported in the literature, encompassing acute myocardial injury, arrhythmia, vasculitis, endothelial dysfunction, thrombotic myocardial infarction and myocarditis. […] This article brings together the latest evidence on CMR characteristics, influencing factors and pathogenesis of myocarditis caused by the COVID-19 mRNA vaccine.

• #31 Q&A: What Causes Rare Instances of Myocarditis After mRNA COVID-19 Vaccines? < Yale School of Medicine

  https://medicine.yale.edu/news-article/qanda-what-causes-rare-instances-of-myocarditis-after-mrna-covid-19-vaccines/

  Myocarditis is a rare side effect of mRNA COVID-19 vaccines, which have been used with great success as protection against the SARS CoV-2 virus and its variants. […] Iwasaki: We considered three hypotheses. One is autoimmune myocarditis, which is when the immune cells start to attack our own host cells. […] Our second hypothesis was myocarditis caused by hypersensitivity. […] And then the third hypothesis is the one that we found to be most likely, which is inflammation-related myocarditis. This is immune cell mediated. We found that activated immune cells like cytotoxic killer cells and myeloid cells are elevated in these patients, which appears to suggest that mRNA vaccine-associated myocarditis is the most consistent with being inflammatory cell-mediated. […] Iwasaki: Autoimmune-related myocarditis is more difficult to treat.

• #32 Q&A: What Causes Rare Instances of Myocarditis After mRNA COVID-19 Vaccines? < Yale School of Medicine

  https://medicine.yale.edu/news-article/qanda-what-causes-rare-instances-of-myocarditis-after-mrna-covid-19-vaccines/

  Whereas inflammation-induced myocarditis is more transientwe actually found that inflammation as well as the immune cell types go back to normal after patients recover. […] Lucas: The other thing thats good is how treatable it is. […] Another point is that if you space the dosing of the mRNA vaccines far enough apart, you might allow time for the waning of the inflammatory response and reduce the risk of myocarditis. […] Iwasaki: Its hard to compare head-to-head, but its important to remember that with infection, you not only get myocarditis, but you also get all these other symptoms and damage to your lungs and other organs. […] Studies have also shown that the severity of disease and length of recovery are greater in myocarditis post-COVID, in contrast to this transient experience of inflammation after vaccination.

• #33 Q&A: What Causes Rare Instances of Myocarditis After mRNA COVID-19 Vaccines? < Yale School of Medicine

  https://medicine.yale.edu/news-article/qanda-what-causes-rare-instances-of-myocarditis-after-mrna-covid-19-vaccines/

  Iwasaki: There could be many reasonsgenetics, hormones, potentially environment. […] In these studies, testosterone was involved in some of the features that we see in vaccine-associated myocarditis. […] Lucas: This is a question we have thought a lot about but one we cant yet answer. […] One speculation is based on our thinking about the different organ systems. […] Iwasaki: We both think vaccines are just a miracle. […] But no medicine is without any side effects. […] So its very important that we understand better what those adverse events are and how theyre mediated so that we can improve on the already amazing vaccines that we have, and also to mitigate any risks further in the future. […] Iwasaki: First of all, myocarditis after vaccination for the most part appears to be transient, and these patients recover.

• #34 COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration

  https://www.mdpi.com/2227-9059/9/8/903

  The ACE2 receptor has structurally critical sites whose integrity determines its activity. […] The proposed mechanism of autoantibodies generation is described. Following administration of adenoviral vector encoding the spike protein, a subsequent inflammatory cascade, stimulated by the individual immune response, activates platelets to generate platelet-factor 4 (PF4). […] SARS-CoV-2 vaccines were reported as safe and effective before their marketing and worldwide distribution by first, second, third phase clinical trials and pooled analyses. […] In February 2021, large-scale epidemiological data started to raise suspicion of coagulopathies, after adenoviral vector-based vaccines reached millions of administered doses both in Europe and United States. […] Despite being rare events, around 1/100 000 recipients, further considerations are warranted and justified the European Medicines Agency (EMA) examination of those cases. […] The etiology has not been fully understood but it has become clear that anti-platelet factor 4 (PF4) antibodies in those patients’ serum were implicated and considered to have a fundamental role in what was initially described as similar to heparin-induced thrombocytopenia (HIT).

• #35 COVID-19 Vaccine Blood Clot – BioTechniques

  https://www.biotechniques.com/immunology/rare-covid-19-vaccine-related-blood-clot-mechanism-uncovered/

  Researchers identify a molecular interaction between the COVID-19 vaccine adenovirus vector and platelet factors which may be the cause of rare blood clots linked to the vaccine. […] The findings indicate that the adenovirus can bind to platelet factor 4 (PF4), involved in inflammation and wound repair, and may be the cause of the rare blood clots. […] Scientists have speculated that the occurrence of the rare blood clots could be linked to the viral vector, used to elicit a protective immune response, as this unusual side-effect does not occur in people administered with the Moderna or Pfizer mRNA COVID-19 vaccines. […] Our data confirms PF4 can bind to adenoviruses, an important step in unraveling the mechanism underlying VITT. […] The researchers found that the receptor of ChAdOx1 tightly binds with PF4 via electrostatic interactions.

• #36 COVID-19 Vaccine Blood Clot – BioTechniques

  https://www.biotechniques.com/immunology/rare-covid-19-vaccine-related-blood-clot-mechanism-uncovered/

  It is thought that this interaction between the adenovirus and PF4 and how it is interpreted by the immune system may cause the body to identify the complex as foreign, resulting in an immune response. […] With a better understanding of the mechanism by which PF4 and adenoviruses interact there is an opportunity to engineer the capsid, or outer shell of the vaccine, to prevent this interaction occurring. […] The team speculates that the VITT mechanism is a result of misplaced immunity as a downstream effect of the adenovirus binding with PF4 and aim to clarify whether this complex is inherently thrombogenic (prone to causing blood clots).

• #37 COVID-19: Immediate hypersensitivity reactions to SARS-CoV-2 vaccines – UpToDate

  https://www.uptodate.com/contents/covid-19-immediate-hypersensitivity-reactions-to-sars-cov-2-vaccines

  COVID-19: Immediate hypersensitivity reactions to SARS-CoV-2 vaccines […] Immediate hypersensitivity reactions typically begin within minutes to an hour of vaccination, and they are the focus of this topic review. […] Immediate reactions to the COVID-19 vaccines have been defined in an international consensus document as „a generalized, systemic allergic reaction with acute onset occurring within four hours of vaccine administration”. […] However, there is scant evidence that immediate reactions to COVID-19 vaccines are immunologic in nature. […] The most severe form of a mast cell-mediated (usually IgE-mediated) reaction is anaphylaxis, which is rapid in onset and may cause death.

• #38

  https://link.springer.com/article/10.1007/s13181-023-00931-9

  Antibody toxicity can arise from an expected effect on the target, an immunologic response to the antibody, or from off-target binding. […] The rationale for using tocilizumab in COVID-19 is that IL-6 blockade could attenuate the hyperinflammatory response to SARS-CoV-2, which resembles cytokine storm. […] The goal of a vaccine is to develop longstanding immunity without exposure to the full disease. […] Vaccines stimulate the production of antibodies that interact with a specific part of the virus (the epitope). […] Possible adverse effects to mRNA vaccines include the generation of autoantibodies, adverse reactions to adjuvants, or diluents, and induction of type I interferon responses. […] The mRNA is packaged into lipid nanoparticles (LNPs) and stabilized with polyethylene glycol.

• #39

  https://link.springer.com/article/10.1007/s12026-023-09357-5

  COVID-19 vaccines are based on new technology (mostly mRNA and viral vector based platforms) and as a result, many people are hesitant to get vaccinated, especially due to reported adverse events. […] In this review, we discuss the potential molecular mechanisms leading to the aforementioned rare adverse events and we also associate them with the various vaccine components and vectors. […] The proposed mechanisms for vaccine induced related allergies are being described below. IgE-mediated reactions, via mast cell activation and degranulation, may occur when allergen specific IgE antibodies bind to FcRI receptors on mast cells and basophiles. […] The most accepted mechanism of induction of thrombotic phenomena is the vaccine-induced immune thrombotic thrombocytopenia (VITT) syndrome.

• #40 Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action | npj Vaccines

  https://www.nature.com/articles/s41541-021-00369-6

  COVID-19 vaccines were developed with an unprecedented pace since the beginning of the pandemic. Several of them have reached market authorization and mass production, leading to their global application on a large scale. This enormous progress was achieved with fundamentally different vaccine technologies used in parallel. mRNA, adenoviral vector as well as inactivated whole-virus vaccines are now in widespread use, and a subunit vaccine is in a final stage of authorization. They all rely on the native viral spike protein (S) of SARS-CoV-2 for inducing potently neutralizing antibodies, but the presentation of this key antigen to the immune system differs substantially between the different categories of vaccines. […] Current COVID-19 vaccines present the spike protein in very different ways to the immune system, and two main categories have to be discerned. The first category consists of mRNA and adenoviral vector vaccines (herein referred to as genetic vaccines), both of which do not contain the spike protein but provide genetic information for its biosynthesis in body cells of the vaccinee.

• #41 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20220914/Mechanism-of-action-of-different-COVID-19-vaccines.aspx

  In a recent study posted to the bioRxiv* preprint server, researchers at the University of Tuebingen and Imperial College London assessed humoral and cellular immune responses elicited by the recombinant adenoviral vector (rAdVV)- and messenger ribonucleic acid (mRNA)-based coronavirus disease 2019 (COVID-19) vaccines. […] Studies have reported that COVID-19 vaccines confer immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inducing antibody (Ab)-based humoral and T lymphocyte-based cellular immune responses. However, there has not yet been an extensive examination of the mechanisms that underlie COVID-19 vaccines. […] The vaccine platforms (rAdVV and mRNA) had distinct and unique immune mechanisms of T lymphocyte activation and antigen presentation by monocytes and dendritic lymphocytes (DCs) that could alter vaccine efficacy outcomes.

• #42 Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action | npj Vaccines

  https://www.nature.com/articles/s41541-021-00369-6

  In this review, we discuss the biosynthesis and relevant structural features of the viral spike as a basis for understanding differences of its presentation in current COVID-19 vaccines. Our major focus is on variations of the constructs for S biosynthesis in genetic vaccines and on possible conformational differences of S in conventional vaccines. […] The potential of the S trimer to adopt different conformations may pose a problem for its use in vaccines, because the native structure required to induce potently neutralizing antibodies may be disrupted during manufacturing of conventional vaccines or when the protein is expressed in cells of the vaccinee after genetic vaccination. […] The different classes of currently available COVID-19 vaccines exhibit fundamental differences with respect to their modes of action and the ways by which the spike antigen is presented to the immune system.

• #43 Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action | npj Vaccines

  https://www.nature.com/articles/s41541-021-00369-6

  The uniting feature of current genetic COVID-19 vaccines is the provision of mRNAs for the whole, membrane-anchored spike protein in tissues after intramuscular application. […] For delivery, the RNA vaccines are formulated as complexes with specific lipids in the form of lipid nanoparticles (LNP), which not only provide protection from RNA degradation in tissues but also facilitate cellular uptake and release into the cytoplasm for RNA translation. […] Compared to mRNA vaccines, adenovirus-vector vaccines comprise several additional layers of complexity that can lead to heterogeneities of immune reactions and adverse effects. […] The unifying feature of all current adenovirus-vaccine vectors is the replacement of one of the early adenoviral genes (E1) for the full-length SARS-Cov-2 S gene in the adenoviral DNA.

• #44 COVID-19: Mechanisms of Vaccination and Immunity

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7564472/

  The clinical trials that are now urgently needed to evaluate the COVID-19 vaccine candidates serve to determine optimal vaccine dose and scheduling and whether multiple booster vaccinations are required. […] The induction of CD4 T cell help is often not rate limiting in vaccination, probably because low numbers of these cells are already sufficient for supporting antibody production. […] It is not recommended to vaccinate for T cell responses without also efficiently inducing neutralizing antibodies, because the latter are likely the crucial key effectors, and also because T cells, particularly CD8 T cells, can cause extended tissue damage through their cytotoxicity against infected cells, which is likely increased in the absence of antibodies that neutralize the viruses in the extracellular space.

• #45 Immunological mechanisms of vaccine-induced protection against COVID-19 in humans | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00578-z

  Current evidence indicates that SARS-CoV-2 does not productively infect macrophages, making enhancement of infection unlikely, and ADE and VAERD have so far not been demonstrated for SARS-CoV-2. […] The potential role of IgG with reduced Fc fucosylation and enhanced binding to FcRIII in the development of severe COVID-19 suggests that the quality of antibodies induced by vaccination may also be important in minimizing the risk of ADE. […] In order to identify correlates and mechanisms of protection without a massive financial outlay and substantial delay, we need to fully utilize the existing data via a data-driven approach to carefully assess which immunological pathways are associated with protection against COVID-19.

• #46 COVID-19: Mechanisms of Vaccination and Immunity

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7564472/

  Together, these data suggest that efficient and safe strategies of vaccination may be achieved by the preferential usage of antigens that display neutralizing epitopes and the relative avoidance of other epitopes to limit the risk through disease enhancing antibodies. Hence, RBD or RIS alone, perhaps combined with the fusion peptide, could be optimal, as other parts of the S protein and the other SARS-CoV-2 surface proteins could be potentially involved in ADE. […] A major hurdle is the very limited pre-existing clinical experience with any coronavirus vaccine, increasing the failure risk of COVID-19 vaccine trials and consequent delay. […] We suggest that COVID-19 vaccines are promising when they induce large quantities of high affinity neutralizing antibodies and only relatively low amounts of other antibodies and immune responses bearing the risk of disease enhancement. Targeted by most neutralizing antibodies, RBD may be the virus Achilles heel.

• #47 COVID-19: New Research Shows How the Virus Enters Our Cells and May Lead to Better Vaccines < Yale School of Medicine

  https://medicine.yale.edu/news-article/covid-19-new-research-shows-how-the-virus-enters-our-cells-may-lead-to-better-vaccines/

  The stable structure in that area suggests future vaccines that target it might be universally effective against more dangerous SARS-CoV-2 variants, and could even work against other coronaviruses, such as the viruses that cause Middle East Respiratory Syndrome (MERS) or the original Severe Acute Respiratory Syndrome (SARS). […] Antibodies against this region are effective against a wide variety of SARS-CoV-2 variants, including so-called variants of concern, which are newly evolved variants that may be more infectious or more transmissible than the original virus. […] The cutting-edge imaging technique combined with the computer models allowed the team to take images of the spike-ACE2 interaction and the following fusion intermediates that had not been seen before with that level of detail.

• #48 Explaining How Vaccines Work | Vaccines & Immunizations | CDC

  https://www.cdc.gov/vaccines/basics/explaining-how-vaccines-work.html

  Vaccines work by imitating an infection to engage the body’s natural defenses. […] The active ingredient in all vaccines is an antigen, the name for any substance that causes the immune system to begin producing antibodies. […] The updated COVID-19 vaccines were developed to deal both with fading immunity and a fast-evolving virus.

• #49 Vaccine Types | HHS.govLock

  https://www.hhs.gov/immunization/basics/types/index.html

  Researchers have been studying and working with mRNA vaccines for decades and this technology was used to make some of the COVID-19 vaccines. mRNA vaccines make proteins in order to trigger an immune response. mRNA vaccines have several benefits compared to other types of vaccines, including shorter manufacturing times and, because they do not contain a live virus, no risk of causing disease in the person getting vaccinated. […] Scientists used this technology to make COVID-19 vaccines as well. Viral vector vaccines use a modified version of a different virus as a vector to deliver protection. Several different viruses have been used as vectors, including influenza, vesicular stomatitis virus (VSV), measles virus, and adenovirus, which causes the common cold. Adenovirus is one of the viral vectors used in some COVID-19 vaccines being studied in clinical trials.

• #50 COVID-19 Vaccine Basics | COVID-19 | CDC

  https://www.cdc.gov/covid/vaccines/how-they-work.html

  The knowledge that was gained through past research on coronavirus vaccines helped speed up the initial development of the current COVID-19 vaccines. […] Results from these trials have shown that COVID-19 vaccines are safe and effective, especially against severe illness, hospitalization, and death.

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