the distinguishing feature of a coronavirus is its:

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. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. Another BPL-inactivated whole-virus vaccine in development (by the European company Valneva) makes use of Alum in combination with CpG to induce preferentially a desired Th1 response138, and a similar effect has been attributed to the Matrix-MTM adjuvant used in the Novavax subunit vaccine99,101,102. Antiviral Res 176, 104742104742 (2020). Graham, C. et al. Uridine depletion and chemical modification increase Cas9 mRNA Activity and reduce immunogenicity without HPLC purification. Cellular immunity predominates over humoral immunity after the first dose of COVID-19 vaccines in solid organ transplant recipients. Lasaro, M. O. Both of these technologies have already been applied successfully to the production of vaccines against other viral diseases84. Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action F. Heinz, K. Stiasny Published 16 August 2021 Biology NPJ Vaccines COVID-19 vaccines were developed with an unprecedented pace since the beginning of the pandemic. 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. Mercado, N. B. et al. Correspondence to 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. Nat. Science 370, 950 (2020). [114] Coronaviruses were first discovered in the . Sci. Zeng, C., Zhang, C., Walker, P. G. & Dong, Y. Formulation and delivery technologies for mRNA vaccines. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N. Engl. Lancet 397, 99111 (2021). 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. Ma, J. et al. Nature 583, 290295 (2020). Specific features of adaptive immune responses are strongly influenced and shaped by innate responses that are triggered by pathogen-associated molecular patterns (PAMPs) and their sensing by pattern recognition receptors (PRRs) (reviewed in ref. Huang, Q. Brun, J. et al. In addition, background expression of remaining adenoviral genes has been demonstrated in this as well as in other studies with human adenovirus-based vectors72,76. ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. Blood 110, 19161923 (2007). Adv. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Irrespective of these categories, all vaccines have to cope with the intrinsic problem of conformational instability of the spike protein, whether it is synthesized in the vaccinee after genetic vaccination or in cell culture systems for production of conventional vaccines. Although all current vaccines for which phase 3 efficacy data are available rely on the whole viral spike protein as an antigen, its presentation to the immune system is strikingly different not only between genetic vaccines and protein-based vaccines, but also between vaccines within these categories. Nat. CrossRef Google Scholar 4 Baker, MA, Sands, KE, Huang, SS, et al. Head-to-head comparisons of mRNA vaccines will be informative to identify and evaluate differences of innate and adaptive responses as well as reactogenicity between representatives of this class of COVID-19 vaccines. 19, 3546 (2020). 5). Lutz, J. et al. 26, 14221427 (2020). Antiviral Res. 1; Black students are more likely than White students to receive harsher consequences . Lancet Infect. And like other coronaviruses that infect people, the new coronavirus causes respiratory disease, among other symptoms. 41). Res. 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 and the flu have many symptoms in common, including: Fever Cough Shortness of breath or difficulty breathing Tiredness Sore throat Runny or stuffy nose Muscle aches Headache Nausea or vomiting, but this is more common in children than in adults The signs and symptoms of both diseases can range from no symptoms to mild or severe symptoms. 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. van Doremalen, N. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. 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. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Zost, S. J. et al. Current COVID-19 vaccines present the spike protein in very different ways to the immune system, and two main categories have to be discerned. 1, 131138 (2021). 21, 950961 (2021). volume6, Articlenumber:104 (2021) Vasileiou, E. et al. RNA sensors of the innate immune system and their detection of pathogens. J. Med.383, 26032615 (2020). Four types cause minor illnesses like the common cold, while other coronaviruses . 4a) and the additional deletion of E319,61,62,64,65,69. Details of manufacturing processes may differ between the companies, and subtle product-specific variations of RNA sequences were recently confirmed by comparative analyses of RNA extracted from original vials of the two vaccines (https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV2-spike-encoding-mRNA-sequences-for-vaccines-BNT-162b2-and-mRNA-1273/blob/main/Assemblies%20of%20putative%20SARS-CoV2-spike-encoding%20mRNA%20sequences%20for%20vaccines%20BNT-162b2%20and%20mRNA-1273.docx.pdf). Voysey, M. et al. 7, 586593 (2021). Immunol 11, 1673 (2020). Commun. 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. Greinacher, A. 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. Drug Discov. 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. There are open questions concerning the structure of S in the inactivated vaccines. 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 . JAMA 324, 951960 (2020). ; Approval of final manuscript: F.X.H. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. COVID-19 dynamics after a national immunization program in Israel. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Suryadevara, N. et al. 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 Cell 184, 23162331.e2315 (2021). Dis. Conceptualization: F.X.H. E1 and E3: Early adenovirus genes 1 and 3, respectively. 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. Kelso, J. M. Anaphylactic reactions to novel mRNA SARS-CoV-2/COVID-19 vaccines. Mol. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. Cleared for takeoff. Despite incompletely resolved questions (e.g. 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. . Assessing antigen structural integrity through glycosylation analysis of the SARS-CoV-2 viral spike. The effect of residual Triton X-100 on structural stability and infection activity of adenovirus particles. Lancet Infect. 65, 1420 (2020). Science 372, 466 (2021). Winkler, E. S. et al. https://doi.org/10.1038/s41591-021-01413-7 (2021). Article Internet Explorer). According to research published in Rhinology, COVID-19 can cause a loss of taste and smell even without congestion. Introduction of two prolines and removal of the polybasic cleavage site lead to higher efficacy of a recombinant spike-based SARS-CoV-2 vaccine in the mouse model. 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. Baldo, A., Leunda, A., Willemarck, N. & Pauwels, K. Environmental risk assessment of recombinant viral vector vaccines against SARS-Cov-2. Google Scholar. Science https://doi.org/10.1126/science.abj9106 (2021). 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. Contaminating cellular proteins can be present in all vaccines involving production in cell culture. Lancet 397, 16461657 (2021). Immunol. Adenovirus 5 is used in the CanSino vaccine and the second dose of Gamaleya vaccines (section Adenovirus-vector vaccines and Table1). Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Med. We thank Leonhard Heinz for critically reading the manuscript. The most striking difference is that COVID-19 can cause a loss of sense and smell. Article 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. 46, 429430 (2021). 3a; see section Vaccine-specific differences of innate responses)51,52. Hodgson, S. H. et al. Efficient formation of such antibodies by B cells requires helper functions of CD4 T cells that are specifically stimulated by peptides derived from the same antigen in complex with MHCII molecules. 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). Encapsulating the RNA genome is the viral envelope (teal . CAS Lancet 397, 18191819 (2021). 5a) (https://patents.google.com/patent/CN111218459B/en). 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. COVID-19's rate of transmission depends on the timely detection of the carrier and the immediate implementation of interventions. Due to their capacity to stimulate innate responses, the genetic vaccines are referred to as being self-adjuvanted55,136. 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 The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by Cryo-EM and Cryo-ET. The recovery count is 11,35,489 and the active caseload is 11, the Brihanmumbai Municipal Corporation official said. Distinct conformational states of SARS-CoV-2 spike protein. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. PubMed Amanat, F. et al. Cagigi, A. COVID-19 Hotline. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Immunol. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Biosci. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Article 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. SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19) People around the world commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1. Solar deities have been integral in the development of cultures across the world. 80). Impact of ribosome activity on SARS-CoV-2 LNPbased mRNA vaccines. Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Brouwer, P. J. M. et al. 7, 512533 (2021). Igyrt, B. & Lor, K. Immune responses induced by mRNA vaccination in mice, monkeys and humans. Distinguishing viral pneumonia from bacterial pneumonia is difficult in the community. The second category encompasses protein-based approaches, i.e. Distinguishing feature definition: If you can distinguish one thing from another or distinguish between two things, you can. Vaccine 39, 44234428 (2021). Independent of such antigenic effects, the fundamentally different mechanisms of action and ways of production are likely to introduce additional variation to the characteristics of immune responses and possible adverse reactions. Amanat, F. et al. and K.S. 13, eabi9915. 21, 181192 (2021). RBDreceptor binding domain; NTDN-terminal domain; FPfusion peptide. PubMed Voss, W. N. et al. Release 333, 511520 (2021). Proc. Front. 384, 18851898 (2021). 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. 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. Nature 595, 344345 (2021). Therefore, isolation of the final product includes detergent solubilization of the cells and several steps of purification101. & Ertl, H. C. New insights on adenovirus as vaccine vectors. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. 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. Each spike is about 20 nm long and is composed of a trimer of the S protein. 2d)24,25,26. Wall, E. C. et al. 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.