. Mol. Dyer, O. Covid-19: Chinese vaccines may need changes to improve efficacy, admits official. Coronavirus disease 19 (COVID-19) has resulted in an estimated 470,000 deaths worldwide to date. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. 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. 12 October 2022. J. 2c)22,23,24. 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. 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. Liang, Z. et al. In parallel to genetic vaccines, more conventional approaches of vaccine development were pursued with similar intensity and led to the authorization of inactivated whole-virus vaccines and a subunit vaccine that is in a stage of pre-authorization (Table1). Li X, et al. 1, 131138 (2021). Research Shows How To Spot Fake News About Coronavirus - Forbes Comparative analyses of antibody and T cell responses and their fine specificities will allow indirect but important conclusions to be drawn. npj Vaccines 5, 91 (2020). Vaccine 39, 21902200 (2021). All current vaccines that are authorized for general use and for which clinical efficacy data have been published rely on the viral spike protein (S) as an immunogen, either alone orin the case of inactivated virus vaccinestogether with other viral proteins present in the viral particle (see sections below). Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies. However, the situation of COVID-19 outbreak is getting worse in other countries over the last few days, such as Italy, America and Spain . Mild or Moderate Covid-19 | NEJM In some cases, however, COVID-19 can lead to respiratory failure, lasting lung and heart muscle damage, nervous system problems, kidney failure or death. 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. Nature 584, 443449 (2020). Folegatti, P. M. et al. Corresponding studies are in progress (Com-Cov study: Oxdorf-AstraZeneca and BionTech-Pfizer, launched in February132). Each spike is about 20 nm long and is composed of a trimer of the S protein. Bangaru, S. et al. Science 369, 956 (2020). To reach this conclusion, the USC researchers studied the rates of symptom incidence in two . 8, 14301435 (2011). volume6, Articlenumber:104 (2021) Cite this article. & Edwards, K. M.) 7583.e72 (Elsevier, 2018). 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. Thiagarajan, K. Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust. Distinguishing characteristics and unknown features are highlighted in the context of protective antibody responses and reactogenicity of vaccines. ACS Central Sci. Science 372, 525 (2021). During transport, S is cleaved into S1 and S2 by the cellular protease furin in the TGN. 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. Effects of pre-existing and vaccination-induced immunity against the vector are a special feature of adenovirus vector vaccines. 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). Hasanpourghadi, M., Novikov, M. & Ertl, H. C. J. COVID-19 vaccines based on adenovirus vectors. Article & Yan, J. SARS-CoV-2 virus: vaccines in development. Science Translational Medicine. The real reason for Ron DeSantis' Disney World district takeover With this kind of vaccines, the specific design of genetic sequences for the correct formation and presentation of properly folded spike proteins to B cells are in the foreground of interest. 27, 12051211 (2021). Science https://doi.org/10.1126/science.abj9106 (2021). Artificial Intelligence Augmentation of Radiologist Performance in Dicks, M. D. J. et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. ACS Central Sci. Mol. Ghosh, S. et al. JAMA 324, 951960 (2020). PDF Retrospective case control study to evaluate hypocalcaemia as a 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. Heinz, F.X., Stiasny, K. Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action. Ella, R. et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. 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. There is indirect evidence that virus strains having emerged later in the pandemic (e.g. Science 373, 642648 (2021). Coronavirus - State of Michigan J. Med. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. Zeng, C., Zhang, C., Walker, P. G. & Dong, Y. Formulation and delivery technologies for mRNA vaccines. 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. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. 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. Article Biosci. Coronavirus - Wikipedia iPad vs. iPad Air: which is right for you? - Hartford Courant The risk of immediate serious infection is thought to be very low. 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. Article b Formation of vaccine particles in production cell line complementing E1 from chromosomally integrated E1 gene. Nat. This classification was based on the following: Detection of cases attributed to Omicron in multiple countries, including among those without travel history. & Ertl, H. C. New insights on adenovirus as vaccine vectors. Vaccines 11, 695719 (2012). Google Scholar. CAS J. Med. J. Med. PubMed Central Coronavirus disease (COVID-19) / Feature stories; COVID feature stories. Genome Med. . Tian, J.-H. et al. Article CrossRef Google Scholar 4 Baker, MA, Sands, KE, Huang, SS, et al. Shaw, R. H. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. The variant gambit: COVID-19s next move. Logunov, D. Y. et al. A. 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. Coronaviruses have enveloped virions (virus particles) that measure approximately 120 nm (1 nm = 10 9 metre) in diameter. Coronavirus is mostly spread through the air, when people are in close contact with each other. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Huang, Q. b Transfected cells: Biosynthesis of S occurs in the absence of interactions with other viral proteins. In one study they collected 15 false and 15 true headlines about Covid-19. Liu, C. et al. Due to their capacity to stimulate innate responses, the genetic vaccines are referred to as being self-adjuvanted55,136. Therefore, the landscape of vaccines becoming available for general use may expand in the near future. "As a council member, I'm disappointed and appalled that no one else would think that there was anything wrong with this report," said Jones, a Democrat who represents District 2. Cureus | Coronavirus (COVID-19): A Review of Clinical Features Investig. CAS 26, 14221427 (2020). In fact, . 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 . Latest News Today on Covid-19, Politics, State Elections, Top India 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. Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation. https://doi.org/10.1038/s41541-021-00369-6, DOI: https://doi.org/10.1038/s41541-021-00369-6. 11, 909 (2020). & Fox, G. J. PubMed Central Commun. Nature 583, 290295 (2020). Reimer, J. M. et al. Coughlan, L. Factors which contribute to the immunogenicity of non-replicating adenoviral vectored vaccines. 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. Wearing a mask over your mouth and nose helps to stop your water . Therefore, other adjuvants or combinations thereof with Alum have been developed for use in COVID-19 vaccines138. J. Med. 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. It is unclear, at present, which influences anti-vector responses will have on necessary COVID-19 booster vaccinations in the future. The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: implications for the design of spike-based vaccine immunogens. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Evidence for antibody as a protective correlate for COVID-19 vaccines. 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. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). Lancet Infect. 80). Collectively, this kind of adverse event is designated vaccine-induced immune thrombotic thrombocytopenia (VITT). npj Vaccines 2, 29 (2017). Tatsis, N. et al. ERendoplasmic reticulum; ERGICendoplasmic reticulum Golgi intermediate compartment; TGNTrans Golgi Network; RNPRibonucleoprotein; Viral proteins: Sspike, Mmembrane; Eenvelope; Nnucleoprotein. Feature stories - World Health Organization 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). Mol. 7, eabe5575 (2021). Eichinger, K. M. 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. b Schematic of a lipidnanoparticle (LNP) used for delivery of mRNA vaccines. N. Engl. COVID-19 vaccine: What's RNA research got to do with it? PubMed Lewis, D. Mix-and-match COVID vaccines: the case is growing, but questions remain. 384, 21872201 (2021). PubMedGoogle Scholar. Blood 110, 19161923 (2007). Nelson, J. et al. Rossman, H. et al. Coronavirus - BBC News 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. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. No, It's Not Surprising That A Nurse Got COVID-19 After His First 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. Zhang, Y. et al. Preprint at https://www.researchsquare.com/article/rs-440461/v1 (2021). What is coronavirus? COVID-19 explained | CNN Voysey, M. et al. 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). 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. Winkler, E. S. et al. 888-535-6136. 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. Fausther-Bovendo, H. & Kobinger, G. P. Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, whats important? Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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. 3a; see section Vaccine-specific differences of innate responses)51,52. In predynastic Egypt, Atum was a solar deity associated with the sun god Ra . Schmidt, T. et al. Sci. 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. 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. Lancet Infect. Extensive modifications by N- and O-glycosylation occur in the compartments encountered by S during its intracellular transport18. Although distinguishing COVID-19 from normal lung or other lung diseases, such as cancer at chest CT, may be straightforward, a major hurdle in controlling the current pandemic is making out subtle radiologic differences between COVID-19 and pneumonia of other origins. Alharbi, N. K. et al. Another inactivated whole-virus vaccine using similar technology is produced by the Indian company Bharat and has received emergency use authorization in India even before completion of phase III clinical trials91 (Table1). Hofman, K., Shenoy, G. N., Chak, V. & Balu-Iyer, S. V. Pharmaceutical aspects and clinical evaluation of COVID-19 vaccines. On the positive side, results of efficacy as well as field effectiveness studies in various countries using different vaccines indicated a high degree of protection also against circulating VOCs, in particular against the Alpha variant2,98,110,111. 384, 20922101 (2021). 4c). 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. Verbeke, R., Lentacker, I., De Smedt, S. C. & Dewitte, H. The dawn of mRNA vaccines: The COVID-19 case. 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. B. et al. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in 21, 195197 (2021). Immunol. Uruguay quietly beats coronavirus, distinguishing itself from its South FEMA helps the public distinguish between rumors and facts regarding the response to the Coronavirus (COVID-19) pandemic. Vogel, A. PubMed 5a) (https://patents.google.com/patent/CN111218459B/en). 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. Interim guidance has been issued by the World Health Organization and by the United States Centers for Disease Control and Prevention [ 2,3 ]. Lancet Infect. Kowalczyk, A. et al. 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. Liu, L. et al. In the BionTech-Pfizer and Moderna vaccines this problem was taken into account by modifications of the RNA sequence and the inclusion of m1 (section mRNA vaccines), which is not contained in CureVacs mRNA vaccine56. In this article, we review the relevance of structural modifications of S in different vaccines and the different modes of antigen expression after vaccination with genetic adenovirus-vector and mRNA vaccines. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. A. et al. The coronavirus at the root of COVID-19 is the newest known member of this family. 384, 18851898 (2021). CAS Janssen-Johnson&Johnson and Gamaleya-Institute use the authentic SARS-CoV-2 S protein signal sequence19,67, whereas CanSino replaced it with that of human tissue plasminogen activator (tPA) (Fig. Release 217, 345351 (2015). 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 . Differentiating viral from bacterial pneumonia - The Centre for Lancet Infect. Cell 184, 18211835.e1816 (2021). 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. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. JAMA 325, 15621565 (2021). 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). 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 . A distinguishing feature of SARSCoV2 is its incorporation of a polybasic site cleaved by furin, which appears to be an important element enhancing its virulence. Science 372, 466 (2021). 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. Cell 183, 15201535.e1514 (2020). 2c)20,21. The potential of the S trimer to adopt different conformations may pose a problem for its use in vaccines, because the native structurerequired to induce potently neutralizing antibodiesmay be disrupted during manufacturing of conventional vaccines or when the protein is expressed in cells of the vaccinee after genetic vaccination. C. R. Biol. 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. Several studies have been conducted to decide whether the chest X-ray and computed tomography (CT) scans of patients indicate COVID-19. and K.S. Ella, R. et al. The precise mechanisms of how the RNA is taken up by different cells after vaccination and escapes from LNPs and intracellular vesicles is incompletely resolved53,55. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Both the Pfizer and Moderna vaccines work by giving the body instructions for how to make a harmless protein that is a distinguishing feature of the actual virus so that when or if the vaccinated person gets exposed to the virus, their body already knows what to do to fight it off. ABCNews.com: What to Know About the Symptoms and Treatment of Norovirus Adenoviral vectors contain PAMPs that can be sensed by TLRs at the plasma membrane (TLR2 and TLR4) and the endosomally located TLR9 (reviewed in ref. The inactivated whole virus vaccine produced by Bharat (Covaxin, Table1) is adjuvanted with an imidazoquinoline class molecule (IMDG, a TLR 7/8 agonist) adsorbed on aluminum hydroxide gel (Algel-IMDG) that shifts the response towards Th197,141,142. 1b). Wall, E. C. et al. A severe complication of COVID-19 is viral pneumonia. Ther. This quantitative aspect is important for future analyses of the impact of waning immunity on protection and decisions about optimal timings of booster immunizations. There is evidence that the Oxford-AstraZeneca vaccine might induce higher levels of specific T cells, whereas mRNA vaccines might induce higher antibody titers115,116,117. Tortorici, M. A. et al. Almuqrin, A. et al. Contaminating cellular proteins can be present in all vaccines involving production in cell culture. Google Scholar. Nature 586, 583588 (2020). 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. Keech, C. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Conceptualization: F.X.H. The extended N-terminal leader sequence results in two consecutive signal peptides separated by an intervening stretch of tPA propeptide (Fig. PubMed CAS 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. It is therefore a major goal of all COVID-19 vaccines to present the spike and its RBD in a most native conformation for inducing a high proportion of potently neutralizing antibodies after vaccination. Cell 183, 10241042.e1021 (2020). Adv. 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. Vaccines 9, 453 (2021). Nature 588, 498502 (2020). Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Kowarz, E. et al. Watanabe, Y. et al. After amplification in bacterial cells, the plasmid DNA is linearized and impurities are removed before in vitro transcription into RNA. Haas, E. J. et al. Wang, H. et al. Earle, K. A. et al. A novel Chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. Corbett, K.S. The results from a hydrogeological study at LithiumBank Resources Corp (TSX-V:LBNK)'s 100%-owned Park Place lithium brine project, located in Alberta are "surprisingly favorable," according to analysts at Noble Capital.. 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. 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. The loss of the E1 gene abolishes replication competence of the vector. CDC director's ABC News interview remarks about COVID-19 victims with What are the parts of a coronavirus? | Scripps Research 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). Cell Host Microbe 29, 508515 (2021). Preprint at https://www.medrxiv.org/content/10.1101/2021.05.07.21256809v1 (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. 2c). 385, 187189 (2021). Coronavirus variants: Facts about omicron, delta and other COVID-19 2ac)20,21. 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. van Doremalen, N. et al. Immunol. 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. Tsiambas, E. et al. Cleared for takeoff. Coronaviruses are a large family of viruses, but only seven of its members infect humans. Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. The total amount of protein per dose was found to be 35 to 40g, most of which can be assumed to be cellular protein, because the protein of 51010 adenovirus particles per dose would account for only about 8g (for calculation see122). Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.