Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. 100, 309354 (2018). Corresponding studies are in progress (Com-Cov study: Oxdorf-AstraZeneca and BionTech-Pfizer, launched in February132). Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Google Scholar. 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. Med. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. Baden, L. R. et al. Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation. 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. Adenovirus 5 is used in the CanSino vaccine and the second dose of Gamaleya vaccines (section Adenovirus-vector vaccines and Table1). 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. CrossRef Google Scholar 4 Baker, MA, Sands, KE, Huang, SS, et al. Pinto, D. et al. The CDC lists these as the most common symptoms of COVID-19: Fever or chills Cough Shortness of breath or difficulty breathing Fatigue Muscle or body aches Headache New loss of taste or smell. We thank Leonhard Heinz for critically reading the manuscript. The low performance may be attributed in part to the high proportion of variants that have caused infections in the study population. Vaccine 39, 865867 (2021). PubMed Central Almuqrin, A. et al. 65, 1420 (2020). This is why it's very important that we socially distance from other people, and wear a mask. Kids face the same risk of catching it as adults, although the disease is usually milder in children. 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). Opin. The study revealed that the vaccine contains vast numbers and amounts of cellular proteins from the human HEK293 production cell line, in addition to adenoviral proteins and the S protein, which is apparently also synthesized already during the manufacturing process. Vaccine 39, 21902200 (2021). COVID-19 Hotline. b Schematic of the process using an additional N-terminal leader sequence (signal peptide and propeptide of tPA), as used in the vaccine of Oxford-Astra Zeneca, based on reference. Four types cause minor illnesses like the common cold, while other coronaviruses . 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. Preprint at https://www.researchsquare.com/article/rs-440461/v1 (2021). Thiagarajan, K. Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust. 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. CAS Animal experiments have shown that adenovirus-vector DNA can remain detectable for months after inoculation in transcriptionally active form82 in contrast to rapidly degraded RNA55,83. 27, 10551061 (2021). J. Med. The European Union teams up with WHO to boost COVID-19 vaccination coverage in Africa. Another mRNA vaccine, manufactured by the company CureVac (current name CVnCoV; Table1) is in an advanced stage of development56. Commun. Vaccines (Basel) 9, 65 (2021). Ther. The RBD oscillates between an up and down position, and interaction with the cellular receptor (ACE2) is only possible with the transiently exposed RBD in the up position20,21. Mumbai Sees Two Covid-19 Cases, No Death; Active Tally Now 11. Nature 586, 567571 (2020). npj Vaccines 2, 29 (2017). 1, 131138 (2021). Curr. https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018215766. Importantly, the human neutralizing antibody response in SARS-CoV-2 infection appears to be dominated by RBD-specific antibodies, whichon averagewere shown to contribute 90% of the total neutralizing activity of human post-infection sera39. The coronavirus and its variants are very contagious. They contain codon-optimized sequences for efficient expression of the full-length S protein and use the authentic signal sequence for its biosynthesis44,45,46,47 (Fig. Despite incompletely resolved questions (e.g. Each dose contains 51010 or 101010 adenoviral particles (Table1), which corresponds to 8 or 16g of adenoviral protein (for calculation see ref. Linares-Fernndez, S., Lacroix, C., Exposito, J.-Y. Haas, E. J. et al. Prevention of infection with the Beta, Gamma and Delta variants might be lower, although evidence indicates substantial protection from severe disease after two vaccinations110,112,113. 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. Different from SARS-CoV and MERS-CoV in genetics and epidemiology, SARS-CoV-2 is a novel -coronavirus [ 6, 7 ]. Hofman, K., Shenoy, G. N., Chak, V. & Balu-Iyer, S. V. Pharmaceutical aspects and clinical evaluation of COVID-19 vaccines. Immunol 11, 1673 (2020). Amanat, F. et al. Prof. Robert Howarth, ecology and evolutionary biology, has advanced climate understanding throughout his career, conducting groundbreaking research and speaking with world leaders. UTRuntranslated region. COVID-19 dynamics after a national immunization program in Israel. Med. Although in vitro model studies with one of the current adenovirus vector vaccines (ChAdOx1 nCoV-19; Table1) have shown that S-coding transcripts dominate the transcription patterns, rare aberrant splicing or polyadenylation site usage were observed72. Lewis, D. Mix-and-match COVID vaccines: the case is growing, but questions remain. Vaccines (Basel) 9, 326 (2021). 1a)15. FEMA helps the public distinguish between rumors and facts regarding the response to the Coronavirus (COVID-19) pandemic. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Internet Explorer). Neutralizing activity was also observed for antibodies against S2, but the potency was lower than of those against S127. And like other coronaviruses that infect people, the new coronavirus causes respiratory disease, among other symptoms. In the CanSino vaccine, the signal peptide of S is replaced by that of human tPA (https://patents.google.com/patent/CN111218459B/en). Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Share information from trusted sources. Front. Phase 1 assessment of the safety and immunogenicity of an mRNA- Lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. b Trimeric pre-fusion spike with one RBD in up position. Nature 584, 443449 (2020). Although corresponding data do not yet exist in the public domain for the other adenoviral vector vaccines, the problem of cellular impurities may be similar, because they all depend on the lysis of production cells for releasing the engineered vector particles (section Adenovirus-vector vaccines). Adjuvants for coronavirus vaccines. They can also spread it to others. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). Immunol. 383, 23202332 (2020). 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. 13, 43 (2021). These subunits remain associated in the trimer through noncovalent interactions, and the virus is probably secreted via exocytic lysosomes with disrupted lysosomal functions17. All of these distinguishing features might provide clues to yet unresolved vaccine-specific determinants of immune responses, efficacy, and potentially adverse reactions. The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by Cryo-EM and Cryo-ET. a Schematic of replication-incompetent adenoviral vector particle and its DNA. Zost, S. J. et al. PubMed 2ac)20,21. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Expert Rev. 384, 20922101 (2021). Details of the engineered leader sequence in the ChAdOX1-S vaccine are difficult to track, but likely comprise 32 to 34 amino acids of tPA (according to a document of the European Medicines Agency assessing thrombotic post-vaccination events, EMA/205598/2021) and may contain a P to A mutation at position 22 to improve processing by signal peptidase80. ; Approval of final manuscript: F.X.H. 137, https://doi.org/10.1080/08820139.2021.1904977 (2021). Coronavirus is mostly spread through the air, when people are in close contact with each other. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. 5b). Antiviral Res 176, 104742104742 (2020). PubMed Eichinger, K. M. et al. Voss, W. N. et al. Cell 182, 713721.e719 (2020). 17, 261279 (2018). 41). Reimer, J. M. et al. CAS Hodgson, S. H. et al. Some spike molecules, not assembled into virions, are also transported to the plasma membrane despite the presence of an ER retention signal15. However, the authors discuss evidence of shedding of the cleaved S1 portion78, which has also been observed in model studies with unmodified S proteins compared to mutationally stabilized proteins18 (Fig. 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. DISTINGUISHING FEATURES OF THE WORK: An employee in this class is responsible for performing basic nursing skills in a clinic or other settings . PLoS ONE 7, e41451 (2012). 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/). Article Drug Discov. Coronavirus disease 19 (COVID-19) has resulted in an estimated 470,000 deaths worldwide to date. The structures were generated with PyMol, using protein data bank (PDB) files 7KRR and 7KRS96 for the pre-fusion forms, 6XRA for the post-fusion form25. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. 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. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. 13, eabi9915. Andreano, E. et al. Irrespective of pre-existing immunity, all adenovirus vector vaccines are prone to induce immune responses against the vector particles129. Research on school discipline disparities has demonstrated three key trends across the country: Black students are more likely than White students to be referred for disciplinary action for subjective infractions such as disruption or defiance compared to objective infractions such as tardiness or truancy. Heath, P. T. et al. Many uncertainties remain in our understanding of the spread of Covid-19 and its management. Dis. There is an urgent need to clarify the pathogenic mechanism underlying the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 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. 19, 3546 (2020). Logunov, D. Y. et al. High-resolution structural analysis revealed that the purified protein is stably locked in the preferred pre-fusion conformation, in part as free trimers and in part as multitrimer complexes103. PubMed Central J. Med. 23, 14561464 (2015). The S protein is in turn composed of an S1 and S2 subunit. Science 369, 650 (2020). Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Antiviral Res. Therefore, isolation of the final product includes detergent solubilization of the cells and several steps of purification101. Coronaviruses are a family of viruses that contain RNA (instead of DNA, like people have). The study, published in Frontiers in Public Health, finds that a distinguishing feature of COVID-19 is the order in which symptoms first appear. he voted for an austerity budget that reduced health services in the middle of the COVID-19 pandemic. Hunter, P. R. Thrombosis after covid-19 vaccination. In some cases, however, COVID-19 can lead to respiratory failure, lasting lung and heart muscle damage, nervous system problems, kidney failure or death. The amount of impurities depends on the purification steps applied in the manufacturing process. SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID 1-3.Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1-3; however, the basic biological mechanisms responsible . 12, 372 (2021). Nature 583, 290295 (2020). J. Virol. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Even though the CT scan is more sensitive to COVID Pneumonia, Chest X-rays used can be for a possible preliminary classification, due to its prevalent usage as a primary diagnostic test. Google Scholar. 384, 21872201 (2021). Nelson, J. et al. At 10.9 inches, the 4th-generation iPad Air boasts a larger screen than the iPad . Adv. Rev. N. Engl. Twitter users slammed a new ad from Hershey's Canada featuring trans woman Fae Johnstone as the face of its "International Woman's Day" campaign. Adenovirus-vector and mRNA vaccines promote substantially different innate responses that will certainly influence the nature of adaptive immune responses43. Development of an inactivated vaccine candidate for SARS-CoV-2. Immunol. On average a coronavirus particle has 74 surface spikes. 11, 589833 (2020). Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Nature 594, 483 (2021). There is indirect evidence that virus strains having emerged later in the pandemic (e.g. Section navigation Coronavirus disease (COVID-19) Feature stories Situation reports; Media resources. Vaccines 12, 379393 (2013). Ther.Nucleic Acids 12, 530542 (2018). 384, 403416 (2021). Immunol. 11, 3618 (2020). a Schematic of the process using the authentic viral signal peptide only (as in the vaccines of BionTech-Pfizer, Moderna, Janssen-Johnson&Johnson and Gamaleya Institute). 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. COVID-19 is a contagious respiratory disease caused by infection with the virus SARS-CoV-2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory. 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. Nature 590, 630634 (2021). Virol. Currently, a slightly but significantly increased risk of thrombotic events (including cerebral venous sinus thrombosis) was reported after vaccination with Oxford-AstraZeneca and Janssen adenovirus vector vaccines and has raised considerable concern74,75. JAMA 325, 12411243 (2021). Recently, data from a phase 3 clinical trial became available, showing a relatively low efficacy of 47% at preventing disease (https://www.curevac.com/en/2021/06/16/curevac-provides-update-on-phase-2b-3-trial-of-first-generation-covid-19-vaccine-candidate-cvncov/), well below the efficacies reported for the BionTech-Pfizer and Moderna vaccines46,47 and below the requirement of at least 50% efficacy proposed by WHO (https://www.who.int/publications/m/item/considerations-for-the-assessment-of-covid-19-vaccines-for-listing-by-who). So far, no data are available that would allow a direct comparison of the various vaccines and their effectiveness against the different VOCs. 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. 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. ACS Central Sci. 9, e42e43 (2021). McCoy, K. et al. The most striking difference is that COVID-19 can cause a loss of sense and smell. Expert Rev. Abu-Raddad, L. J., Chemaitelly, H. & Butt, A. Hum. The first category consists of mRNA and adenoviral vector vaccines (herein referred to as genetic vaccines, sections: Genetic vaccinesgeneral, mRNA vaccines, Adenovirus-vector vaccines), both of which do not contain the spike protein but provide genetic information for its biosynthesis in body cells of the vaccinee. 21, 181192 (2021). Blumenthal, K. G. et al. Google Scholar. 11, 909 (2020). Although the animal reservoir for the SARS and MERS viruses are known . Cell 184, 39363948.e3910 (2021). Chen, N. et al. 2c)20,21. The effect of dissociation of soluble S1 from the trimer complex on the quality of immune responses is incompletely understood, but some data suggest it may contribute to a higher proportion of non-neutralizing relative to neutralizing antibodies19,81. Zhang, J. et al. While these efforts resulted in successful classification systems, the design of a portable and cost-effective COVID-19 diagnosis system has not been addressed yet. Dev. Despite the absence of S2-stabilizing mutations, structural studies of the S protein expressed in HeLa cells from the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine provided evidence for proper folding and presentation of the trimeric pre-fusion conformation at the cellular plasma membrane78. 4b)70. 21, 3951 (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). The two mRNA vaccines in current widespread application (BioNTech-Pfizer and Moderna) (Table1) are technologically very similar. A plethora of viral mutants arose and spread since the emergence of SARS-CoV-2104,105. Google Scholar. 88) could not be found in the literature. Vaccines 11, 695719 (2012). They are known to infect the neurological, respiratory, enteric, and hepatic systems. Dis. Bos, R. et al. c Expression of spike in cells of vaccinated individuals. 2d)19. Mol. In the following sections, we will discuss these basic differences, and provide information on variations and modifications that can affect the structural integrity of the spike in genetic and conventional vaccines. The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: implications for the design of spike-based vaccine immunogens. Studies are emerging that address antibody formation to the different domains of S and analyze the ratio of neutralizing and non-neutralizing antibodies as an important parameter of vaccine performance145,146. The coronavirus at the root of COVID-19 is the newest known member of this family. Preprint at https://www.medrxiv.org/content/10.1101/2021.05.07.21256809v1 (2021). Baldo, A., Leunda, A., Willemarck, N. & Pauwels, K. Environmental risk assessment of recombinant viral vector vaccines against SARS-Cov-2. Sometimes a common cold can inhibit your sense of smell or taste, but this is due to mucus build-up and congestion. J. Med. Opin. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. Google Scholar. Science. Dis. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. -Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway. The virus spreads through respiratory droplets released when someone breathes, coughs, sneezes, talks or sings. 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. Therefore, other adjuvants or combinations thereof with Alum have been developed for use in COVID-19 vaccines138. 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. Mol. Understanding of COVID-19 is evolving. Adv. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. Google Scholar. 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. Ebright helped The Washington Post debunk a claim that the COVID-19 outbreak can somehow be tied to bioweapons activity, a conspiracy theory that's been promoted or endorsed by the likes of US Sen. Tom Cotton, Iran's supreme leader, and others. Conceptualization: F.X.H. Most of the allergens are proteins, which are not contained in these chemically defined vaccines (section mRNA vaccines). 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. Immunol. Liu, C. et al. Ther. ; Visualization: F.X.H. Wiener Klinische Wochenschrift 133, 271283 (2021). Microbiol. b Transfected cells: Biosynthesis of S occurs in the absence of interactions with other viral proteins. Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccinesa new era in vaccinology. 5b), based on a previous study with Middle East respiratory syndrome coronavirus (MERS-CoV79 (Fig. N. Engl. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. Xia, S. et al. Brun, J. et al. 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. Blood 110, 19161923 (2007). N. Engl. The findings of the MIT team suggest that interferon's potential role in fighting Covid-19 may be complex. Barouch, D. H. et al. 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. Nature https://doi.org/10.1038/s41586-021-03777-9 (2021). 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. Winkler, E. S. et al. Lancet 396, 479488 (2020). Impact of mRNA chemistry and manufacturing process on innate immune activation. Such effects have been specifically shown for the ionizable lipid component in LNPs124. SPsignal peptide; SRPsignal recognition particle; tPAtissue plasminogen activator; ERendoplasmic reticulum; C-terC terminus; N-terN terminus. Sadoff, J. et al. Article Cai, Y. et al. Biosci. Literature data indicate that production of the Sinovac vaccine includes several steps of virus purification, leading to a product that contains primarily the viral proteins and consists of essentially pure viral particles86,87. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. Nat. When S is synthesized as an isolated protein (Fig. PubMed 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. Hasan, T., Beardsley, J., Marais, B. J., Nguyen, T. A. Current COVID-19 vaccines present the spike protein in very different ways to the immune system, and two main categories have to be discerned. Nature 586, 583588 (2020). Each monomer of S is composed of several structural elements, including the N-terminal domain (NTD) and receptor-binding domain (RBD) in S1, which occlude the S2 moiety in the native S trimer (Fig. 2d)24,25,26. The viral RNA is sneaky: its features cause the protein synthesis . Trends Biochem. This complex artificial sequence element may lead to some inhomogeneity in proteolytic processing and impairment of correct formation of the S N-terminus during biosynthesis, as recently shown in comparative model studies with similar constructs19. Contaminating cellular proteins can be present in all vaccines involving production in cell culture. Comparative analyses of antibody and T cell responses and their fine specificities will allow indirect but important conclusions to be drawn. Nat. . Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Effects of pre-existing and vaccination-induced immunity against the vector are a special feature of adenovirus vector vaccines. Lancet https://doi.org/10.1016/s0140-6736(21)01462-8 (2021). 29 January 2023. & Fox, G. J. 80). Nature 584, 437442 (2020). Lancet 397, 16461657 (2021). 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). Several of the 291 candidates listed in the COVID-19 vaccine pipeline by WHO (184 pre-clinical and 107 in clinical development) (https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines, accessed on July 9, 2021), have already reached the market and are used for mass immunization. Cell cultures are also used for production of the inactivated whole-virus vaccines (Vero cells) of Sinopharm88, Sinovac86 and Bharat97 as well as for the Novavax subunit vaccine (insect Sf9 cells)99,101 (sections Inactivated vaccines and Subunit vaccines and Table1). Information on cellular impurities are so far restricted to ChAdOx1 and comparative analyses of all adenovector vaccines are not yet available. a Infected cells: Subgenomic mRNAs for viral structural proteins are translated in association with the ER (S, M, and E) or in the cytoplasm (N), and virus assembly takes place in the ERGIC. Vaccine 35, 37803788 (2017). Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. Xu, C. et al. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD and S2. Lancet 397, 13511362 (2021). 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.