key: cord-305587-xtqvtleb authors: Ma, Cuiqing; Su, Shan; Wang, Jiachao; Wei, Lin; Du, Lanying; Jiang, Shibo title: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development date: 2020-05-11 journal: Microbes Infect DOI: 10.1016/j.micinf.2020.05.004 sha: doc_id: 305587 cord_uid: xtqvtleb The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics. In December 2019, the outbreak of an unexplained pneumonia similar to severe acute 32 respiratory syndrome (SARS) in Wuhan, China was reported by the Health Commission of Hubei 33 Province, China. This severe respiratory illness was identified by multiple diagnostic methods as an 34 infection by a novel coronavirus (1) (2) (3) (4) , which was temporarily denoted as 2019-nCoV by World 35 Health Organization (5) ， and renamed "severe acute respiratory syndrome coronavirus 2" against SARS-CoV using their own vaccine platforms (33) (34) (35) (36) (37) . However, most vaccines are in preclinical studies, and only a few of them have been reported to under assessment in clinical trials 111 (https://clinical trials.gov/ct2/show/nct03615911; https://clinical trials.gov/ct2/show/nct0339578). 112 Currently, no vaccine has been approved for the prevention of SARS. Since effective antiviral 113 strategies to control SARS-CoV and SARS-CoV-2 infections are still lacking, vaccination is still 114 regarded as the major approach for preventing potential re-emergence of SARS-CoV, and more 129 It is known that most of the current influenza vaccines are inactivated vaccines, which plays a and is crucial for determining host tropism and transmission capacity (61, 62) . Generally, the S protein 189 of coronavirus is functionally divided into the S1 subunit, responsible for receptor binding, and the generating S1 and S2 subunits is located at R694/S695 (67) . In addition, it has been reported that S 193 protein has strong immunogenicity and can induce high titer neutralizing antibody (63) . RBD of 194 SARS-CoV S1 is located in S318-510 and the key RBM is S425-494, of which R453 is critical for for the whole protein, around 73%-76% for the RBD, and 50%-53% for the RBM (7, 30) . In S1 subunit, SARS-CoV-2 and SARS-CoV shared around 50 conserved amino acids, and the 204 three-dimensional structure of SARS-CoV-2 RBD was composed of a core and an external 205 subdomain, which was more similar to that of SARS-CoV (29) . We aligned the sequence of S protein protective immunity (35, (78) (79) (80) . For example, the expression of full-length S protein and its trimer of recombinant S1 or S2 proteins, respectively, and found that anti-S1 and anti-S2 IgGs were able to 304 abolish the binding between S protein and its cellular receptor(s), although anti-S1 IgG showed a 305 significantly higher blocking efficiency (106) . As shown in Figure 2B , the amino acid sequences of 306 HR1 and HR2 are highly conserved and homologous between SARS-CoV and SARS-CoV-2. In fact, 307 these domains are also highly conserved in other coronaviruses (104) , thus the S2 subunit has potential 308 to be used as a target for the development of pan-CoV vaccine against divergent virus strains. Altogether, these results suggested that the S2 domain of SARS-CoV S protein, as a vaccine RBDs. The red number indicates the core amino acids in RBD when it binds to receptor ACE2. The green frame is the amino acid sequence of RBM. B. Sequence alignment of SARS-CoV and SARS-CoV-2 HR1. The red frame is the location where the variable amino acid residues between SARS-CoV and SARS-CoV-2 HR1. Importation and human-to-human 437 transmission of a novel coronavirus in Vietnam A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome Nowcasting and forecasting the potential domestic and international spread of the 441 2019-nCoV outbreak originating in Wuhan, China: a modelling study Coronavirus-Infected Pneumonia Transmission dynamics of 2019 novel coronavirus Novel coronavirus 2019-nCoV: early estimation of 447 epidemiological parameters and epidemic predictions Modelling the epidemic trend of the 2019 novel coronavirus outbreak in China Dynamically modeling SARS and other newly emerging respiratory 452 illnesses: past, present, and future Epidemiology and cause of severe acute respiratory syndrome 454 (SARS) in Guangdong, People's Republic of China Epidemiological determinants of spread of 456 causal agent of severe acute respiratory syndrome in Hong Kong Epidemiological and clinical characteristics of 99 cases of 2019 458 novel coronavirus pneumonia in Wuhan, China: a descriptive study First case of 2019 novel coronavirus in the 460 United States Discovery of seven novel Mammalian and avian 462 coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus 463 and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus Epidemiology, genetic recombination, and pathogenesis of 466 coronaviruses Molecular evolution of human coronavirus genomes Origin and evolution of pathogenic coronaviruses The 2019-new coronavirus epidemic: 471 evidence for virus evolution Structural and functional basis of SARS-CoV-2 entry by using 482 human ACE2 Inhibition of SARS-CoV-2 infections in 484 engineered human tissues using clinical-grade soluble human ACE2 SARS vaccine development Characterization of humoral responses in mice 488 immunized with plasmid DNAs encoding SARS-CoV spike gene fragments The spike protein of SARS-CoV -A target for vaccine and therapeutic 491 development Peptide nanoparticles as novel 493 immunogens: design and analysis of a prototypic Severe Acute Respiratory Syndrome Vaccine Development of subunit vaccines against severe acute respiratory syndrome The COVID-19 vaccine 498 development landscape Immunogenicity of SARS inactivated vaccine in 500 BALB/c mice A subcutaneously injected UV-inactivated 502 SARS coronavirus vaccine elicits systemic humoral immunity in mice Inactivated SARS-CoV vaccine prepared from whole virus induces a 504 high level of neutralizing antibodies in BALB/c mice Identification and characterization of novel neutralizing epitopes in the 506 receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated 507 SARS-CoV vaccine Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies 509 that block receptor binding and virus entry Immunization with SARS 511 coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus Glycan arrays lead to the discovery of autoimmunogenic activity of SARS-CoV Evaluation of antibody-dependent enhancement of SARS-CoV infection in 515 rhesus macaques immunized with an inactivated SARS-CoV vaccine Rationalizing the development of live attenuated virus vaccines Engineering attenuated virus vaccines by controlling replication fidelity Severe acute respiratory syndrome 521 coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice Adenoviral expression of a truncated S1 Intranasal vaccination of recombinant adeno-associated virus 533 encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces 534 strong mucosal immune responses and provides long-term protection against SARS-CoV infection Immunization with modified vaccinia virus 537 Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in 538 ferrets A live, impaired-fidelity coronavirus vaccine 540 protects in an aged, immunocompromised mouse model of lethal disease Evaluation of a recombination-resistant coronavirus as a 542 broadly applicable, rapidly implementable vaccine platform Safety and immunogenicity from a Phase I trial of inactivated severe acute 544 respiratory syndrome coronavirus vaccine A SARS DNA vaccine induces 546 neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial Structure, function, and evolution of coronavirus spike proteins A pan-coronavirus fusion inhibitor targeting the HR1 550 domain of human coronavirus spike Bat-to-human: spike features determining 'host jump'of coronaviruses SARS-CoV, MERS-CoV, 552 and beyond MERS-CoV spike protein: Targets for vaccines and therapeutics Receptor-binding domain of SARS-CoV spike protein induces highly 556 potent neutralizing antibodies: implication for developing subunit vaccine Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 559 domain in spike protein Functional analysis of an epitope in the S2 subunit of the murine coronavirus spike protein: 69 Cross-host evolution of severe acute respiratory 571 syndrome coronavirus in palm civet and human Identification of two critical amino acid residues of the 573 severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double 574 substitution strategy Structural analysis of major species barriers between humans and palm civets for severe acute respiratory 576 syndrome coronavirus infections Receptor recognition and cross-species infections of SARS coronavirus Mechanisms of host receptor adaptation by severe acute respiratory 579 syndrome coronavirus A 193-amino acid fragment of the SARS coronavirus S protein 581 efficiently binds angiotensin-converting enzyme 2 A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus 583 spike protein disrupts the antigenic structure and binding activity Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a 585 highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate 586 membrane fusion Antibodies against trimeric S glycoprotein 588 protect hamsters against SARS-CoV challenge despite their capacity to mediate FcγRII-dependent entry into B cells in 589 vitro A 219-mer CHO-expressing receptor-binding domain of SARS-CoV S 591 protein induces potent immune responses and protective immunity Recombinant receptor-binding domain of SARS-CoV spike 593 protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity Antigenic and immunogenic characterization of recombinant 596 baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design Anti-severe Acute Respiratory Syndrome Coronavirus 599 spike antibodies trigger infection of human immune cells via a pH-and cysteine protease-Independent FcγR pathway Antibody-dependent SARS coronavirus infection is 602 mediated by antibodies against spike proteins SARS CoV subunit vaccine: antibody-mediated 604 neutralisation and enhancement Anti-spike IgG causes severe acute lung injury by skewing 606 macrophage responses during acute SARS-CoV infection The role of CD4 and CD8 T cells in MHV-JHM-induced demyelination Immunodominant SARS coronavirus epitopes in humans 610 elicited both enhancing and neutralizing effects on infection in non-human primates Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies 613 primarily targeting the receptor binding region Identification of a critical neutralization determinant of severe acute 615 respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines Identification of murine CD8 T cell epitopes in 617 codon-optimized SARS-associated coronavirus spike protein Antigenicity and immunogenicity of SARS-CoV S protein 619 receptor-binding domain stably expressed in CHO cells Receptor-binding domain of severe acute respiratory syndrome coronavirus 621 spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. The 622 MERS-CoV spike protein: a key target for antivirals Advances in MERS-CoV vaccines and therapeutics based on the 626 receptor-binding domain Receptor-binding domain of SARS-CoV spike protein induces 628 long-term protective immunity in an animal model Priming with rAAV encoding RBD of SARS-CoV S protein and 630 boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against 631 SARS-CoV infection Searching for an ideal vaccine candidate among different 633 MERS coronavirus receptor-binding fragments-the importance of immunofocusing in subunit vaccine design Cross-neutralization of human and palm civet severe acute 636 respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein Potent binding of 2019 novel coronavirus spike protein by a SARS 639 coronavirus-specific human monoclonal antibody SARS-CoV fusion peptides induce membrane surface 641 ordering and curvature Expression and characterization of recombinant S2 subunit of SARS-coronavirus S 643 fusion protein Evaluation of candidate vaccine approaches for 645 MERS-CoV A novel neutralizing monoclonal antibody targeting the 647 N-terminal domain of the MERS-CoV spike protein Human monoclonal antibodies against highly conserved 649 HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing Elicitation of immunity in mice after immunization with the S2 651 subunit of the severe acute respiratory syndrome coronavirus Quantitative comparison of the efficiency of antibodies 653 against S1 and S2 subunit of SARS coronavirus spike protein in virus neutralization and blocking of receptor binding: 108 Specific asparagine-linked glycosylation sites are critical for DC-SIGN-and 661 L-SIGN-mediated severe acute respiratory syndrome coronavirus entry Current advancements and potential strategies in the development of MERS-CoV vaccines Identification of an ideal adjuvant for 665 receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus Virus detectives seek source of SARS in China's wild animals Isolation and characterization of viruses related to the SARS 669 coronavirus from animals in southern China Bats are natural reservoirs of SARS-like coronaviruses Severe acute respiratory syndrome coronavirus-like virus 673 in Chinese horseshoe bats Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease cGAS produces a 2'-5'-linked cyclic dinucleotide 677 second messenger that activates STING Cyclic GMP-AMP is an endogenous second messenger in innate 679 immune signaling by cytosolic DNA Pivotal roles of cGAS-cGAMP signaling in antiviral defense and 681 immune adjuvant effects Pulmonary surfactant-biomimetic nanoparticles potentiate 683 heterosubtypic influenza immunity Prospects for a dengue virus vaccine Don't rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees