the distinguishing feature of a coronavirus is its:

The importance of distinguishing COVID-19 from more common respiratory Nature https://doi.org/10.1038/s41586-021-03777-9 (2021). Vaccines (Basel) 9, 61 (2021). One of the constituents discussed as being causally linked to anaphylaxis is polyethylene glycol (PEG), which is used in the formulation of LNPs that protect the RNA and facilitate its transfer into cells (section mRNA vaccines). Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. The S protein is in turn composed of an S1 and S2 subunit. Coutard, B. et al. containing the mutation D614G in S) may be more stable95,96 and therefore could serve as an improved substrate for the production of inactivated vaccines. Phase 1 assessment of the safety and immunogenicity of an mRNA- Lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. Distinguishing viral pneumonia from bacterial pneumonia is difficult in the community. Cleared for takeoff. Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine. Science 370, 1089 (2020). 1, 131138 (2021). Science 373, 642648 (2021). There is an urgent need to clarify the pathogenic mechanism underlying the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pinto, D. et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. FEMA helps the public distinguish between rumors and facts regarding the response to the Coronavirus (COVID-19) pandemic. Cell 183, 10241042.e1021 (2020). This halo of spikes is what led scientists to name these "coronaviruses.". . https://doi.org/10.1056/NEJMoa2108891 (2021). Eye Opener: Alex Murdaugh faces possible life sentence for murder of wife and son Guilty on all counts, disgraced South Carolina attorney Alex Murdaugh now faces possible life in prison for the . Preprint at https://www.biorxiv.org/content/10.1101/2021.04.20.440647v2 (2021). 65, 1420 (2020). Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. 384, 403416 (2021). Bangaru, S. et al. Nat. iScience 24, 102298 (2021). Nat. Wrapp, D. et al. 3,4 Although the . It has been speculated that pre-existing PEG antibodies might be involved in these allergic events124. J. Med. Lancet 397, 671681 (2021). Bos, R. et al. Experts know the new coronavirus is not a bioweapon. They disagree on Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials. Results from a phase 1 clinical trial with the Curevac vaccine had indeed already shown relatively low titers of neutralizing antibodies induced by the dose used in the phase 3 clinical trial56,59. Correlates of protection against SARS-CoV-2 in rhesus macaques. The low performance may be attributed in part to the high proportion of variants that have caused infections in the study population. These considerations of vector immunity also prompted the development of non-human adenovirus vectors such as ChAdOx1 derived from chimpanzee adenovirus Y2564, now used in the Oxford-AstraZeneca vaccine77. A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, identified genomic features of SARS-CoV-2, the virus that causes COVID-19, and other high-fatality coronaviruses that distinguish them from other members of the coronavirus family. 21, 950961 (2021). RSV vs. COVID-19 Coronavirus: Symptoms and Their Differences - WebMD N. Engl. In predynastic Egypt, Atum was a solar deity associated with the sun god Ra . In vitro transcription is followed by several steps of mRNA purification, including the removal of dsRNA, which could lead to an excessive innate immune response and concomitant reactogenicity48,50. In the course of cellular SARS-CoV-2 infection (Fig. Omicron quickly spread around the world, causing a surge of COVID-19 cases in December 2021 and January 2022. They are known to infect the neurological, respiratory, enteric, and hepatic systems. mBio 12, e0264802620 (2021). Latin America is the world's new coronavirus epicenter, but Uruguay - a small South American nation of 3.5 million people - has so far avoided the devastation raging across the rest of the . Front. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Logunov, D. Y. et al. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018215766. (Image credit: Daedalean) Daedalean is looking to get its AI certified with both the FAA (Federal Aviation Administration) and EASA (European Union Aviation Safety Agency . 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. Nelson, J. et al. We also address the grey matter of additional variables, such as ill-defined downstream production processes and purity of vaccines as well as differences in triggering sensors of innate immunity. Daedalean: the AI copilot looking for permission to fly They use derivatives of different adenoviruses as vectors for reasons more specifically discussed in section Distinguishing features of vaccines independent of immunogen, as follows: CanSinohuman adenovirus 561, Janssen-Johnson&Johnsonhuman adenovirus 2619,62,63, Oxford-AstraZenecachimpanzee adenovirus Y2564,65,66; Gamaleya Institutehuman adenovirus 26 for the first vaccination and human adenovirus 5 for the second67,68. Vogel, G. Mixing COVID-19 vaccines appears to boost immune responses. BMJ 373, n958 (2021). Amanat, F. et al. Adv. In addition, approaches to cope with the problem of the lability of the viral S protein cause variation across all current vaccines. RNA sensors of the innate immune system and their detection of pathogens. 5G mmWave: Facts and fictions you should definitely - Android Authority Coronaviruses | Microbiology Society https://doi.org/10.1038/s41541-021-00369-6, DOI: https://doi.org/10.1038/s41541-021-00369-6. Thiagarajan, K. Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust. Although the animal reservoir for the SARS and MERS viruses are known . Liu, L. et al. 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. Differentiating viral from bacterial pneumonia - The Centre for 48, 6572 (2021). Article SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. 17, 261279 (2018). Suryadevara, N. et al. PubMed Virus-receptor interactions of glycosylated SARS-CoV-2 spike and human ACE2 receptor. Zost, S. J. et al. The trigger comprises binding of RBD to ACE2 and a further proteolytic cleavage by cellular proteases (in addition to the furin cleavage between S1 and S2) at the so-called S2 site, resulting in the removal of a small sequence element and the exposure of the fusion peptide at the N-terminus of S2 (Fig. Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors. The two mRNA vaccines in current widespread application (BioNTech-Pfizer and Moderna) (Table1) are technologically very similar. Coronaviruses are a family of viruses that can cause respiratory illness in humans. 46, 429430 (2021). Vaccine-Induced Covid-19 Mimicry Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. Nanomaterial delivery systems for mRNA vaccines. Tumban, E. Lead SARS-CoV-2 candidate vaccines: expectations from phase III Trials and recommendations post-vaccine approval. 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. The real reason for Ron DeSantis' Disney World district takeover PubMed 2c, d). Current COVID-19 vaccines are very different with respect to their compositions and modes of action, and therefore vaccine-induced innate responses will vary considerably. Mercado, N. B. et al. Although the constructs for all four adenovirus-vector vaccines contain the full-length spike protein, there are some differences in construct design with respect to mutations for stabilizing S as well as to the signal peptide at the N-terminus of S that require attention. Coronavirus disease 2019 (COVID-19), the highly contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a catastrophic effect on the world's demographics resulting in more than 6 million deaths worldwide, emerging as the most consequential global health crisis since the era of the influenza Head-to-head comparisons of current mRNA vaccines with respect to possible differences in the efficiency of protein translation, stability or the stimulation of innate responses are not available in the literature. Nature 592, 283289 (2021). The current global pandemic, caused by the coronavirus SARS-CoV-2, emerged in December 2019. The spikes are the most distinguishing feature of coronaviruses and are responsible for the corona- or halo-like surface. It is unclear, at present, which influences anti-vector responses will have on necessary COVID-19 booster vaccinations in the future. npj Vaccines 2, 29 (2017). Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. 5a) (https://patents.google.com/patent/CN111218459B/en). The authors speculate that such secreted forms may bind to ACE2-expressing endothelial cells and could contribute to thrombotic events via antibody-mediated mechanism as observed after vaccination with adenovirus vector COVID-19 vaccines74,75 (see also section Reactions due to vaccine constituents other than the immunogen). PEGpolyethyleneglycol. Delrue, I., Verzele, D., Madder, A. Nature 586, 578582 (2020). Conceptualization: F.X.H. Public Health Nurse I (Mobile County Health Department) In the meantime, to ensure continued support, we are displaying the site without styles Fausther-Bovendo, H. & Kobinger, G. P. Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, whats important? International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. CAS Ther. A total of six species have been identified to cause disease in humans. Krause, P., Fleming, T. R., Longini, I., Henao-Restrepo, A. M. & Peto, R. COVID-19 vaccine trials should seek worthwhile efficacy. Cellular immunity predominates over humoral immunity after the first dose of COVID-19 vaccines in solid organ transplant recipients. In both instances, the virus is grown in Vero cells and inactivated by beta-propiolactone (BPL), which is used as an inactivating agent for other viral vaccines, including rabies vaccines85. Science 369, 956 (2020). ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. CrossRef Google Scholar 4 Baker, MA, Sands, KE, Huang, SS, et al. J. The World Health Organization (WHO) has increased the assessment of the risk of spread and the risk of impact of COVID-19 to very high at a global level . Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. 7, 586593 (2021). Science. Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Zhao, P. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Possible remedies are prime-boost regimens as already used for vaccination with the Gamaleya-Institute vaccine (Ad26 followed by Ad5) or combinations with other classes of vaccines such as mRNA vaccines. Nat. Share information from trusted sources. N. Engl. Trends Biochem. Opin. In addition to direct triggers of innate immunity by RNA, other constituents of LNPs can contribute to vaccine-induced inflammatory reactions and provide adjuvant activity for adaptive immune responses. Club-shaped glycoprotein spikes in the envelope give the viruses a crownlike, or coronal, appearance. Production cell lines for the Oxford-AstraZeneca, Gamaleya and CanSino vaccines are derived from primary human embryonic kidney cells (HEK293), and for the Janssen vaccine from human embryonic retinal cells (PER.C6) (Table1). Cureus | Coronavirus (COVID-19): A Review of Clinical Features Variations include (but are not limited to) the type of adenovirus used as a vector, genetic modifications of the vector, the cell lines used for vaccine production, procedures for purification, and the specific design of the gene for expressing S (Table1). A. et al. Rubin, R. COVID-19 vaccines vs variantsdetermining how much immunity is enough. Both constructs include the two stabilizing mutations in S2 (K986P and V987P) that were shown to prevent the conformational change of the pre-fusion into the post-fusion structure of S (section Introduction and Fig. COVID-19: Clinical features - UpToDate Lancet 397, 18191819 (2021). Potently neutralizing and protective human antibodies against SARS-CoV-2. Voss, W. N. et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Chen, N. et al. Med. Dis. Emary, K. R. W. et al. Eichinger, K. M. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. CAS Rossman, H. et al. Vaccine 35, 37803788 (2017). Article 13, eabi9915. 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. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Igyrt, B. 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 (Fig. Feature stories - World Health Organization J. The virus spreads through respiratory droplets released when someone breathes, coughs, sneezes, talks or sings. 6, eaaz6893 (2020). COVID-19 Email. Tsiambas, E. et al. 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. No, It's Not Surprising That A Nurse Got COVID-19 After His First . Rev. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. 26, 14221427 (2020). Article c Expression of spike in cells of vaccinated individuals. 27, 10551061 (2021). Published information about the production process is available for two inactivated whole-virus vaccines manufactured by the Chinese companies Sinopharm and Sinovac (Table1). Alum is the most frequently used adjuvant in human vaccines and is used in the Sinopharm and Sinovac vaccines137,138. Innate responses to RNA that enters cells from the outside (such as in RNA virus infections or mRNA vaccination) differ from those stimulated by adenoviruses, because RNA is sensed by other PRRs, including TLR3, TLR7 and TLR8, all located in endosomes134,135. Zhang, J. et al. The viruses are circular in shape with spikes on the surface, which appear like a halo when the virus is viewed with a microscope. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. Distinct conformational states of SARS-CoV-2 spike protein. Severe acute respiratory syndrome, also known as SARS, is the other coronavirus that can cause more severe symptoms. Fund. BMJ 372, n196 (2021). Have you got a cold or Covid? Here's how to tell the difference Buschmann, M. D. et al. Sci. J. Med. Nature 588, 498502 (2020). Correspondence to Barouch, D. H. et al. N. Engl. The signal sequence is cleaved off by signal peptidase attached to the inner ER membrane, generating the final N-terminus of the viral spike protein (14-QCVNL). Do your part to the stop the spread of rumors by doing three easy things: Find trusted sources of information. SARS-CoV-2 - Wikipedia We have reviewed the most apparent and significant differences among the vaccines as far as they can be recognized from published literature, which unfortunately is still incomplete. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. COVID-19 vaccine: What's RNA research got to do with it? Immunol. Vaccines 9, 453 (2021). What are the parts of a coronavirus? | Scripps Research Biosci. Persistence of RNA and its expression after different routes of application (including intramuscular) appears to be short (at least in mice), with a maximum of 10 days60. These also differ with respect to their degree of purity (presence of extraneous proteins from the production process) and other vaccine constituents that can affect immune responses and cause adverse events. The potency of these antibodies depends on high-affinity interactions with specific parts of the complex three-dimensional structure of the spike in a native conformation10,11. Some spike molecules, not assembled into virions, are also transported to the plasma membrane despite the presence of an ER retention signal15. You may also have heard about "low band" frequencies and "sub-6GHz," both of which are also part of the standard . 2c). Polack, F. P. et al. Uridine depletion and chemical modification increase Cas9 mRNA Activity and reduce immunogenicity without HPLC purification. According to published literature, manufacturing of the Sinovac and Novavax vaccines involves extensive purification procedures86,101, suggesting that the antigenic contents of these products consists primarily of the proteins of the virus particle or the isolated spike trimer, respectively. Proteolytic cleavage into S1 and S2 occurs in the TGN similar to that in infected cells, but some shedding of cleaved S1 and conversion of S2 into its post-fusion structure (S2*) may occur in the absence of stabilizing mutations. J. Med. Sci. Google Scholar. Wang, H. et al. Understanding of COVID-19 is evolving. Jagannathan, P. & Wang, T. T. Immunity after SARS-CoV-2 infections. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. Other components of cellular immunity, such as CD8 T cells, also contribute to immune responses after SARS-CoV-2 infection or vaccination, although their role in COVID-19 infections and protection from disease is still incompletely resolved12,13. Preprint at https://www.medrxiv.org/content/10.1101/2021.05.07.21256809v1 (2021). Adjuvants for coronavirus vaccines. Immunol. Head-to-head comparisons of vaccinated cohorts will be especially insightful, considering the profound differences of antigen presentation and principles of action of current COVID-19 vaccines. The two protease cleavage sites are indicated by arrows. Dis. Like many other viruses, SARS-CoV-2 is an RNA virus. Mol. Dis. Heath, P. T. et al. Impact of mRNA chemistry and manufacturing process on innate immune activation. Both mRNA vaccines have modulated 5 and 3 untranslated sequences to optimize mRNA stability and translation efficiency44,45, and all uridines are replaced by N1-methylpseudouridine (m1) to further increase RNA stability and to reduce innate immune responses (Fig. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Verbeke, R., Lentacker, I., De Smedt, S. C. & Dewitte, H. The dawn of mRNA vaccines: The COVID-19 case. ; Approval of final manuscript: F.X.H. 2). The amount of impurities depends on the purification steps applied in the manufacturing process. Science 369, 643 (2020). Coronavirus symptoms tend to begin in certain order: Fever first, then Article Z., Jacobsen, S. & Ndeupen, S. Future considerations for the mRNA-lipid nanoparticle vaccine platform. In most people, common cold symptoms usually peak within the first two to three days of infection, while the effects of Covid appear two to 14 days after exposure. a Schematic of the vaccine mRNA in BionTech-Pfizer and Moderna vaccines. Impact of ribosome activity on SARS-CoV-2 LNPbased mRNA vaccines. Therefore, isolation of the final product includes detergent solubilization of the cells and several steps of purification101. Currently, four adenovirus-vector vaccines are in widespread use. Immunol. Comparison of Clinical Features of COVID-19 vs Seasonal - JAMA An infection often resolves quickly and can appear similar to food poisoning. Corresponding studies are in progress (Com-Cov study: Oxdorf-AstraZeneca and BionTech-Pfizer, launched in February132). Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Rochelle Walensky, director of the U.S. Centers for Disease Control and Prevention (CDC), during a meeting with President Biden and members of the White House Covid-19 Response Team on the Omicron . Our modern-day corona conceptualization of club-shaped spikes on the coronavirus surface comes from traditional representations of crowns as radiate headbands, worn as symbols of sovereign power, to liken that power to that of the sun. Lancet 397, 16461657 (2021). Lewis, D. Mix-and-match COVID vaccines: the case is growing, but questions remain. Nat. Rochman, N. D. et al. 21, 181192 (2021). Therefore, other adjuvants or combinations thereof with Alum have been developed for use in COVID-19 vaccines138. Liu, C. et al. 3b)53,54. Dolgin, E. CureVac COVID vaccine let-down spotlights mRNA design challenges. Front. Constituents in the Oxford-AstraZeneca vaccine were recently analyzed in the context of a search for potential causes of venous sinus thrombosis as a rare post-vaccinal complication121. 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 (Fig. Corbett, K. S. et al. 384, 20922101 (2021). The team ran the headlines through a rigorous fact checking. Nature 586, 583588 (2020). Nat. Both modifications are intended to avoid conversion of S into the post-fusion structure (Fig. Coronavirus is mostly spread through the air, when people are in close contact with each other. Vaccin Immunother. Distinguishing features of current COVID-19 vaccines: knowns and volume6, Articlenumber:104 (2021) Cell Host Microbe 29, 508515 (2021). Lutz, J. et al. N. Engl. Some manufacturers have therefore introduced stabilizing mutations that are intended to prevent inadvertent structural conversion of the labile S protein. 22, 539540 (2021). This classification was based on the following: Detection of cases attributed to Omicron in multiple countries, including among those without travel history. Lancet 396, 467478 (2020). Hum. As of mid-March 2022, omicron is the dominant coronavirus variant in the world . A severe complication of COVID-19 is viral pneumonia. Nat. Lancet 397, 20432046 (2021). Vaccines (Basel) 9, 65 (2021). The components used for LNP formulation include phospholipids, cholesterol, special cationic (ionizable) lipids and polyethylene glycol (PEGylated) lipids that are mixed in a sophisticated and critical production step (parts of which are not documented in the published literature) to yield the final vaccine53. People become infected when they then touch their hands to their mouth, nose or eyes. The vaccine produced by Bharat is indeed based on a seed virus containing this mutation97 (Table1). iPad vs. iPad Air: which is right for you? - Hartford Courant PubMedGoogle Scholar. Top. N. Engl. 8, 654866 (2021). The study, published in Frontiers in Public Health, finds that a distinguishing feature of COVID-19 is the order in which symptoms first appear. b Formation of vaccine particles in production cell line complementing E1 from chromosomally integrated E1 gene. Immunol. d Trimeric post-fusion structure of S2, with the three dissociated S1 subunits, shaded in light colors. Recent work by Kowarz et al.73 provides further evidence for alternative splice events that might lead to the formation of C-terminally truncated and therefore soluble S protein. 5). Cagigi, A. After amplification in bacterial cells, the plasmid DNA is linearized and impurities are removed before in vitro transcription into RNA. Therefore, it is urgent to know the epidemic . If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. You are using a browser version with limited support for CSS. JAMA 324, 951960 (2020). Planas, D. et al. There are open questions concerning the structure of S in the inactivated vaccines. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Earle, K. A. et al. Antiviral Res. Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines. Science Translational Medicine. Nature 584, 443449 (2020). NIH researchers identify key genomic features that could differentiate Distinguishing feature definition: If you can distinguish one thing from another or distinguish between two things, you can. They can also spread it to others. Collectively, this kind of adverse event is designated vaccine-induced immune thrombotic thrombocytopenia (VITT). & Stiasny, K. Profiles of current COVID-19 vaccines. Prof. Robert Howarth, ecology and evolutionary biology, has advanced climate understanding throughout his career, conducting groundbreaking research and speaking with world leaders. b Trimeric pre-fusion spike with one RBD in up position. Greinacher, A. et al. Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action, https://doi.org/10.1038/s41541-021-00369-6. Preprint at https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1 (2020). 21, 637646 (2021). Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. These modifications (indicated in Table1 and in the discussion of individual vaccines below) include two proline mutations in S2 (K986P and V987P) at the junction between two alpha helices in the pre-fusion form to avert their fusogenic conformational switch into a long alpha helix in the post-fusion form, and mutations that abolish furin cleavage between S1 and S2 to maintain the pre-fusion trimer and to prevent shedding of S118 (Fig.