& Weissman, D. Recent advances in mRNA vaccine technology. Lutz, J. et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Specifically developed and improved ionizable lipids are used in the Moderna and Biontech-Pfizer vaccines (designated Lipid H, SM-102 and ALC-0315, respectively), which together with the molar ratios of the lipid components in LNPs play a critical role for RNA delivery54. BMJ 373, n969 (2021). Dis. & Nauwynck, H. J. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges. Correlates of protection against SARS-CoV-2 in rhesus macaques. 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. Science 370, 950 (2020). Both vaccines use aluminum hydroxide as an adjuvant. 19, 3546 (2020). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Kids face the same risk of catching it as adults, although the disease is usually milder in children. They can also spread it to others. 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. J. Each spike is about 20 nm long and is composed of a trimer of the S protein. Distinguishing feature definition: If you can distinguish one thing from another or distinguish between two things, you can. 3,4 Although the . Science 372, 1108 (2021). Prof. Robert Howarth, ecology and evolutionary biology, has advanced climate understanding throughout his career, conducting groundbreaking research and speaking with world leaders. Google Scholar. Hofman, K., Shenoy, G. N., Chak, V. & Balu-Iyer, S. V. Pharmaceutical aspects and clinical evaluation of COVID-19 vaccines. Earle, K. A. et al. Cellular immunity predominates over humoral immunity after the first dose of COVID-19 vaccines in solid organ transplant recipients. 384, 20922101 (2021). Cai, Y. et al. Front. Lopez Bernal, J. et al. Article Such effects have been specifically shown for the ionizable lipid component in LNPs124. & Fox, G. J. Google Scholar. Burki, T. K. Challenges in the rollout of COVID-19 vaccines worldwide. 133). 81, 65946604 (2007). The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute . Voss, W. N. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. 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. ; Writing: F.X.H. Sophisticated analyses of the ChAdOx1 nCoV-19 vaccine to elucidate underlying pathogenic mechanisms suggest that constituents such as viral DNA and/or cellular proteins can favor the formation of antibodies against platelet factor 4 (PF4), thus promoting VITT74,121. 2c)20,21. Franz X. Heinz or Karin Stiasny. Solar deities have been integral in the development of cultures across the world. Lancet Respiratory Med. 4B, right) and further downstream processes for the removal of cellular components and free viral DNA71. This adjuvant results in polarization towards a Th2 response, which has been regarded as unfavorable in the case of coronavirus and other viral infections and vaccinations118,139,140. 22, 539540 (2021). Towards understanding ChAdOx1 nCov-19 vaccine-induced immune thrombotic thrombocytopenia (VITT). Gilbert, S. C., Hill, A. V. & Morris, S. J. Compositions and Methods for Inducing an Immune Response. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Zeng, C., Zhang, C., Walker, P. G. & Dong, Y. Formulation and delivery technologies for mRNA vaccines. Club-shaped glycoprotein spikes in the envelope give the viruses a crownlike, or coronal, appearance. Thank you for visiting nature.com. The current global pandemic, caused by the coronavirus SARS-CoV-2, emerged in December 2019. Manipulations of the authentic viral signal sequence may cause inhomogeneities of the N-terminus and impair native folding of S19 (see also section Adenovirus-vector vaccines and Fig. Science 369, 650 (2020). Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. ISSN 2059-0105 (online). The addition of a 5 cap structure is a critical part of this production step that has been improved by new technology suitable for large-scale production48,49. Preprint at https://www.biorxiv.org/content/10.1101/2021.04.14.439844v1 (2021). Blood 110, 19161923 (2007). In addition, the viral DNA itself can be sensed after endosomal rupture by cytosolic DNA sensors such as cGAS and the inflammasome, resulting in downstream signaling cascades for producing antiviral factors such as type I interferons41. Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. Conceptualization: F.X.H. 383, 23202332 (2020). https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018215766. Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation. PubMed . Nat. 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. . One of Johnson's distinguishing features is his long-standing relationship with the Chicago Teachers Union. Nature 588, 498502 (2020). PubMedGoogle Scholar. Therefore, isolation of the final product includes detergent solubilization of the cells and several steps of purification101. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. 7, 594602 (2021). Igyrt, B. CrossRef Google Scholar 4 Baker, MA, Sands, KE, Huang, SS, et al. Evidence for antibody as a protective correlate for COVID-19 vaccines. RNA vaccines contain fully functional mRNAs that can be translated directly into the S protein, whereas additional biosynthetic steps are required with adenovirus vector vaccines, including intranuclear transcription of the vector DNA into RNA and processing to generate functional mRNAs. & Stiasny, K. Profiles of current COVID-19 vaccines. | Meaning, pronunciation, translations and examples COVID-19 Hotline. It has been speculated that pre-existing PEG antibodies might be involved in these allergic events124. 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). Vaccine 39, 44234428 (2021). The implementation of mass-vaccination against SARS-CoV-2: a systematic review of existing strategies and guidelines. Curr. Lancet https://doi.org/10.1016/s0140-6736(21)01462-8 (2021). According to research published in Rhinology, COVID-19 can cause a loss of taste and smell even without congestion. Electron microscopical pictures of the viral spikes in the Sinovac vaccine have been interpreted differently, either as displaying the pre-fusion structure86 or the post-fusion structure25,92. van Doremalen, N. et al. In conclusion, since the emergence of COVID-19 pneumonia and due to its similar radiological patterns, we believe that a SARS-CoV-2 RT-PCR should be systematically realized in case of respiratory . 48, 6572 (2021). Gao, Q. et al. Control. Brouwer, P. J. M. et al. J. Med. 8, 654866 (2021). 13, eabi9915. Another mRNA vaccine, manufactured by the company CureVac (current name CVnCoV; Table1) is in an advanced stage of development56. 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. Different from SARS-CoV and MERS-CoV in genetics and epidemiology, SARS-CoV-2 is a novel -coronavirus [ 6, 7 ]. Center for Virology, Medical University of Vienna, Vienna, Austria, You can also search for this author in Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Barnes, C. O. et al. Lancet 396, 887897 (2020). Details of these processes, affecting the purity and quality of the final vaccines (containing at least 51010 particles per dose), are not accessible in the published literature (see section Contaminations from cell substrates). To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Like many other viruses, SARS-CoV-2 is an RNA virus. https://doi.org/10.1038/s41591-021-01413-7 (2021). 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. Researchers looking at New York City health cases split up COVID-19 patients into clusters based on distinguishing features, including obesity, to form a "decision tree" for statistical analysis . Corresponding scientific investigations into the mechanisms of vaccine-induced anaphylactic reactions are ongoing125. Vogel, A. Greaney, A. J. et al. 2). 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. Bos, R. et al. Haas, E. J. et al. Science https://doi.org/10.1126/science.abj9106 (2021). This pertains to many well-used licensed vaccines such as those against influenza, measles and rabies120. Cell 181, 281292.e286 (2020). Bangaru, S. et al. Our review is limited to those vaccines in current use for which phase 3 clinical efficacy data have been reported, and for which published information on the nature and manufacturing process exists. Mol. The European Union teams up with WHO to boost COVID-19 vaccination coverage in Africa. 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. N. Engl. ACS Central Sci. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. 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. In fact, . Immunol. Polack, F. P. et al. Nance, K. D. & Meier, J. L. Modifications in an emergency: the role of N1-methylpseudouridine in COVID-19 vaccines. 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 . These vaccines are now used worldwide for mass immunization programs, and data on vaccine efficacies justify the hope that vaccination can indeed be the main instrument for preventing serious disease and death, and more generally for combating the pandemic1,2,3,4. Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. Hopefully, more details will become available in the near future. 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. A comprehensive review of the global efforts on COVID-19 vaccine development. Cell 183, 10241042.e1021 (2020). ; Approval of final manuscript: F.X.H. Several studies have been conducted to decide whether the chest X-ray and computed tomography (CT) scans of patients indicate COVID-19. 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. Liu, C. et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. The often-milder symptoms of a Covid-19 breakthrough infection in vaccinated peoplesometimes including a runny nose or sneezing can make it even harder to distinguish between the two illnesses,. A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. The diseases caused by these viruses also share similar clinical presentations, including fever and respiratory symptoms that range from mild forms, such as cough, to severe lung infections. Lancet 397, 671681 (2021). Fan, X., Cao, D., Kong, L. & Zhang, X. Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein. There is indirect evidence that virus strains having emerged later in the pandemic (e.g. ERendoplasmic reticulum; ERGICendoplasmic reticulum Golgi intermediate compartment; TGNTrans Golgi Network; RNPRibonucleoprotein; Viral proteins: Sspike, Mmembrane; Eenvelope; Nnucleoprotein. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. Vaccin Immunother. Coutard, B. et al. Impact of ribosome activity on SARS-CoV-2 LNPbased mRNA vaccines. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. Finn, T. M. & Egan, W. Vaccine Additives and Manufacturing Residuals in Vaccines Licensed in the United States. Robbiani, D. F. et al. Vasileiou, E. et al. These data can serve as an indirect measure for the structural integrity of S in the vaccines and the quality of B cell immune responses. Mol. Correspondence to However, the absence of interactions with other viral components for particle assembly may modulate glycosylation patterns and stability of the S trimers. Nature 586, 578582 (2020). Shimizu, K., Sakurai, F., Machitani, M., Katayama, K. & Mizuguchi, H. Quantitative analysis of the leaky expression of adenovirus genes in cells transduced with a replication-incompetent adenovirus vector. This enormous progress was achieved with fundamentally different vaccine technologies used in parallel. Zhao, P. et al. Tang, T., Bidon, M., Jaimes, J. he voted for an austerity budget that reduced health services in the middle of the COVID-19 pandemic. COVID-19 is a contagious respiratory disease caused by infection with the virus SARS-CoV-2. As a consequence of these changes, the S1 subunits dissociate from the trimer, releasing S2 from its constraints in the pre-fusion conformation to allow an irreversible conversion into a characteristic elongated post-fusion structure (Fig. For reducing potential negative effects of pre-existing immunity, alternative adenoviruses were developed as vectors, one of them adenovirus 26, which has lower rates of seropositivity in the population127 and is now used in the Janssen-Johnson&Johnson vaccine19,62 as well as in the first shot of the Gamaleya-Institute vaccine67,68. Barouch, D. H. et al. Cell Host Microbe 29, 508515 (2021). Preprint at https://www.researchsquare.com/article/rs-558954/v1 (2021). Comparative analyses of antibody and T cell responses and their fine specificities will allow indirect but important conclusions to be drawn. Virus particles are transported through the TGN and released from the cells probably via lysosomes. Fausther-Bovendo, H. & Kobinger, G. P. Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, whats important? 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). 12 October 2022. Alharbi, N. K. et al. Nature 594, 483 (2021). J. Med. Because of its essential functions during viral entry (receptor binding and membrane fusion), the S protein is the major target of antibodies that can potently neutralize the virus. Some people infected with the coronavirus have mild COVID-19 illness, and others have no symptoms at all. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Science 373, 642648 (2021). Dev. Production of potently neutralizing antibodies requires the interaction of B cells with the native protein, most likely by recognition of the spike anchored in the plasma membrane of S-expressing cells (Fig.1b). 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. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Coronaviruses are a large family of viruses, but only seven of its members infect humans. A plethora of viral mutants arose and spread since the emergence of SARS-CoV-2104,105. duration of immunity, prevention of transmission, and protection against emerging virus variants) the availability of effective COVID-19 vaccines is an enormous relief and certainly a great success story already now. Luckily, Apple is known for its uncompromising screen standards, and the new iPad and iPad Air are no different. Only the Janssen vaccine contains S-stabilizing mutations (Table1), comprising not only the two prolines in S2 but also the S1/S2 furin cleavage site, which is mutated from 682-RRAS-685 to SRAG19,62. Zost, S. J. et al. Lancet Infect. 384, 21872201 (2021). Prefusion RSV F immunization elicits Th2-mediated lung pathology in mice when formulated with a Th2 (but not a Th1/Th2-balanced) adjuvant despite complete viral protection. The S protein is in turn composed of an S1 and S2 subunit. Science 369, 956 (2020). Mol. Cell 184, 18041820.e1816 (2021). Opin. Zhang, J. et al. The spikes are the most distinguishing feature of coronaviruses and are responsible for the corona- or halo-like surface. High rates of seropositivity against adenovirus 5 (the pioneer of adenovirus vector development) have been reported in the population126,127, and a number of studies have shown that pre-existing vector immunity can impair the response to the vaccine antigen128,129,130. Christina Marriott, chief executive of the Royal Society for Public Health says: "Growing evidence shows that people who've received two doses of the vaccine typically present . COVID-19, short for "coronavirus disease 2019," is caused by the novel coronavirus SARS-CoV-2. Rossman, H. et al. 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). Protein-based vaccines such as inactivated whole-virus vaccines or subunit vaccines are usually not sufficiently immunogenic on their own and require the addition of adjuvants. . Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Nature https://doi.org/10.1038/s41586-021-03777-9 (2021). N. Engl. Dyer, O. Covid-19: Chinese vaccines may need changes to improve efficacy, admits official. In a note to clients, the analysts wrote that the hydrogeological study indicates Park Place hosts a combined 76.3 cubic kilometres of lithium-bearing brine, meaning . Vaccines (Basel) 9, 61 (2021). RNA sensors of the innate immune system and their detection of pathogens. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Wearing a mask over your mouth and nose helps to stop your water . The virus spreads through respiratory droplets released when someone breathes, coughs, sneezes, talks or sings. The coronavirus disease 2019 (COVID-19) pandemic is currently spreading worldwide and contributing to widespread mortality. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Alum is the most frequently used adjuvant in human vaccines and is used in the Sinopharm and Sinovac vaccines137,138. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV. Lancet 396, 479488 (2020). SARS has an estimated fatality rate of 9% and MERS of 36%. Tsiambas, E. et al. b Trimeric pre-fusion spike with one RBD in up position. The RNA in this vaccine is also codon-optimized and contains modifications to improve its performance, butdifferent from the BioNTech-Pfizer and Moderna mRNA vaccines described aboveit does not contain the m1 nucleoside modifications57,58. Tortorici, M. A. et al. Therefore, for production of the engineered particles as a vaccine, immortalized helper cell lines are used that contain the E1 gene in their chromosomal DNA and provide the missing function, allowing the biosynthesis of structural proteins, replication of modified genomic DNA, and finally assembly of replication-incompetent virus particles in the cells (Fig. Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccinesa new era in vaccinology. Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Brun, J. et al. JCI Insight 4, e123158 (2019). It is unclear, at present, which influences anti-vector responses will have on necessary COVID-19 booster vaccinations in the future. Details of purification procedures of the Bharat vaccine and the degree of cellular contaminants in the Sinopharm vaccine (which is less purified than that of Sinovac according to ref. 5a) (https://patents.google.com/patent/CN111218459B/en). The major problem, however, appears to reside in the relatively low dose of 12g RNA that had to be chosen to avoid intolerably strong side reactions in the absence of RNA modifications such as the m1 nucleoside modifications used in the two authorized mRNA vaccines59. Article 65, 1420 (2020). 385, 187189 (2021). PubMed International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Greinacher, A. et al. Mol. 2d)19. In Plotkins Vaccines 7th edn (eds Orenstein, W. A., Offit, P. A. Pinto, D. et al. SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription. Release 217, 345351 (2015). (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 . 5a) may be especially critical for obtaining natively folded S, because there is a cysteine immediately downstream of the cleavage site (amino acid 2) that has to form an S-S bond with the cysteine at position 136. You are using a browser version with limited support for CSS. Collectively, there are subtle differences between the two vaccines, both with respect to the RNA and the LNP carriers, and a higher amount of RNA per dose is used in the Moderna vaccine (100g) than in the BioNTech-Pfizer vaccine (30g)46,47. Adenovirus 5 is used in the CanSino vaccine and the second dose of Gamaleya vaccines (section Adenovirus-vector vaccines and Table1). PLoS ONE 7, e41451 (2012). Excessive innate responses can not only result in strong reactogenicity of vaccination but also restrict antigen translation from the vaccine RNA, thus impairing adaptive immune responses. Four types cause minor illnesses like the common cold, while other coronaviruses . 2c)22,23,24. 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. Capone, S. et al. Vaccines 11, 695719 (2012). Tumban, E. Lead SARS-CoV-2 candidate vaccines: expectations from phase III Trials and recommendations post-vaccine approval. distinguishing feature of COVID-19 compared with other infective pneumonias and its association with disease severity Meera Mehta ,1 Hakim Ghani ,1 Felix Chua,2,3 Adrian Draper,4 Sam Calmonson,1 Meghna Prabhakar,1 Rijul Shah,1 Alessio Navarra,1 Tejal Vaghela,1 Andrew Barlow,1 Rama Vancheeswaran1 In principle, all current vaccines are affected similarly by VOCs, because they are all based on original wild-type strains from the early phase of the pandemic (see Table1) and therefore their S protein sequences differ from those of VOCs to the same degrees. The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by Cryo-EM and Cryo-ET. 1, 131138 (2021). Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. Uridine depletion and chemical modification increase Cas9 mRNA Activity and reduce immunogenicity without HPLC purification. Share information from trusted sources. b Formation of vaccine particles in production cell line complementing E1 from chromosomally integrated E1 gene. The extended N-terminal leader sequence results in two consecutive signal peptides separated by an intervening stretch of tPA propeptide (Fig. Tatsis, N. et al. On one hand, it can stimulate genes that fight off infection or help cells survive damage, but on the other hand, it may provide extra targets that help the virus infect more cells. In addition, approaches to cope with the problem of the lability of the viral S protein cause variation across all current vaccines. Vaccine 35, 37803788 (2017). ; Visualization: F.X.H. The production process of vaccine mRNAs involves the cloning of the corresponding sequence into a plasmid DNA containing a DNA-dependent RNA-polymerase promoter. At 10.9 inches, the 4th-generation iPad Air boasts a larger screen than the iPad . Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals. Expert Rev. Release 333, 511520 (2021). Preprint at https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1 (2020). The company formulates the S trimer as a nanoparticle in polysorbate 80 (PS80) detergent and uses a special proprietary saponin-based adjuvant (Matrix-M) that comprises 40nm particles composed of Quillaja saponins, cholesterol and phospholipids102,103. Baden, L. R. et al. Graham, C. et al. 21, 83100 (2021). Similar to mRNA vaccines, adenovirus vector vaccines are intended to result in the production of native S proteins from a specific mRNA in cells of the vaccinee (Figs. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Emary, K. R. W. et al. A number of monoclonal antibodies were isolated from COVID-19 patients and used for antigenic characterization of the S trimer, including 3D structure determinations of complexes between S (or parts thereof) and antibody Fab fragments. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material. 12, 372 (2021). 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. BMJ 373, n958 (2021). Convergent antibody responses to SARS-CoV-2 in convalescent individuals. The uniting feature of current genetic COVID-19 vaccines is the provision of mRNAs for the whole, membrane-anchored spike protein (Figs. The impact of COVID-19 on healthcare-associated infections. It consists of the trimeric full-length spike that is produced as a recombinant protein in insect Sf9 (Spodoptera frugiperda) cells using a baculovirus expression system and contains mutations to stabilize S2 (K986P and V987P) as well as to delete the furin cleavage site (682-RRAS-685 changed to QQAQ)99 (Table1 and Fig. Zost, S. J. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Mol. CAS Some of these mutants are considered Variants of Concern (VOCs) because of their highly efficient transmission, the concomitant replacement of previously circulating strains, and the presence of mutations in the spike protein that can lead to immune escape (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/). So far, results of phase III clinical efficacy trials were reported and published for a single subunit vaccine only98, which is manufactured by the company Novavax (NVX-CoV2373) (Table1)98,99 and is still in a stage before regulatory approval100.