The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines
Identifieur interne : 000080 ( Pmc/Corpus ); précédent : 000079; suivant : 000081The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines
Auteurs : Weilong Shang ; Yi Yang ; Yifan Rao ; Xiancai RaoSource :
- NPJ Vaccines [ 2059-0105 ] ; 2020.
Abstract
The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.
Url:
DOI: 10.1038/s41541-020-0170-0
PubMed: 32194995
PubMed Central: 7060195
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines</title><author><name sortKey="Shang, Weilong" sort="Shang, Weilong" uniqKey="Shang W" first="Weilong" last="Shang">Weilong Shang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Yang, Yi" sort="Yang, Yi" uniqKey="Yang Y" first="Yi" last="Yang">Yi Yang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rao, Yifan" sort="Rao, Yifan" uniqKey="Rao Y" first="Yifan" last="Rao">Yifan Rao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rao, Xiancai" sort="Rao, Xiancai" uniqKey="Rao X" first="Xiancai" last="Rao">Xiancai Rao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32194995</idno><idno type="pmc">7060195</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060195</idno><idno type="RBID">PMC:7060195</idno><idno type="doi">10.1038/s41541-020-0170-0</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000080</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000080</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines</title><author><name sortKey="Shang, Weilong" sort="Shang, Weilong" uniqKey="Shang W" first="Weilong" last="Shang">Weilong Shang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Yang, Yi" sort="Yang, Yi" uniqKey="Yang Y" first="Yi" last="Yang">Yi Yang</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rao, Yifan" sort="Rao, Yifan" uniqKey="Rao Y" first="Yifan" last="Rao">Yifan Rao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Rao, Xiancai" sort="Rao, Xiancai" uniqKey="Rao X" first="Xiancai" last="Rao">Xiancai Rao</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">NPJ Vaccines</title><idno type="eISSN">2059-0105</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C Huang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Grohskopf, La" uniqKey="Grohskopf L">LA Grohskopf</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Regla Nava, Ja" uniqKey="Regla Nava J">JA Regla-Nava</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eyigun, Cp" uniqKey="Eyigun C">CP Eyigun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schoeman, D" uniqKey="Schoeman D">D Schoeman</name></author><author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Donaldson, Ef" uniqKey="Donaldson E">EF Donaldson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Sq" uniqKey="Shi S">SQ Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gralinski, Le" uniqKey="Gralinski L">LE Gralinski</name></author><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, W" uniqKey="He W">W He</name></author><author><name sortKey="Mullarkey, Ce" uniqKey="Mullarkey C">CE Mullarkey</name></author><author><name sortKey="Miller, Ms" uniqKey="Miller M">MS Miller</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bukreyev, A" uniqKey="Bukreyev A">A Bukreyev</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, Z" uniqKey="Song Z">Z Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holshue, Michelle L" uniqKey="Holshue M">Michelle L. 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Lofy</name></author><author><name sortKey="Wiesman, John" uniqKey="Wiesman J">John Wiesman</name></author><author><name sortKey="Bruce, Hollianne" uniqKey="Bruce H">Hollianne Bruce</name></author><author><name sortKey="Spitters, Christopher" uniqKey="Spitters C">Christopher Spitters</name></author><author><name sortKey="Ericson, Keith" uniqKey="Ericson K">Keith Ericson</name></author><author><name sortKey="Wilkerson, Sara" uniqKey="Wilkerson S">Sara Wilkerson</name></author><author><name sortKey="Tural, Ahmet" uniqKey="Tural A">Ahmet Tural</name></author><author><name sortKey="Diaz, George" uniqKey="Diaz G">George Diaz</name></author><author><name sortKey="Cohn, Amanda" uniqKey="Cohn A">Amanda Cohn</name></author><author><name sortKey="Fox, Leanne" uniqKey="Fox L">LeAnne Fox</name></author><author><name sortKey="Patel, Anita" uniqKey="Patel A">Anita Patel</name></author><author><name sortKey="Gerber, Susan I" uniqKey="Gerber S">Susan I. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">NPJ Vaccines</journal-id><journal-id journal-id-type="iso-abbrev">NPJ Vaccines</journal-id><journal-title-group><journal-title>NPJ Vaccines</journal-title></journal-title-group><issn pub-type="epub">2059-0105</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32194995</article-id><article-id pub-id-type="pmc">7060195</article-id><article-id pub-id-type="publisher-id">170</article-id><article-id pub-id-type="doi">10.1038/s41541-020-0170-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Comment</subject></subj-group></article-categories><title-group><article-title>The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0752-5016</contrib-id><name><surname>Shang</surname><given-names>Weilong</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-3707-5052</contrib-id><name><surname>Yang</surname><given-names>Yi</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Rao</surname><given-names>Yifan</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2444-4733</contrib-id><name><surname>Rao</surname><given-names>Xiancai</given-names></name><address><email>raoxiancai@126.com</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>Department of Microbiology, College of Basic Medical Sciences,</institution><institution>Army Medical University (Third Military Medical University),</institution></institution-wrap>400038 Chongqing, China</aff></contrib-group><pub-date pub-type="epub"><day>6</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>6</day><month>3</month><year>2020</year></pub-date><pub-date pub-type="collection"><year>2020</year></pub-date><volume>5</volume><elocation-id>18</elocation-id><history><date date-type="received"><day>11</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>21</day><month>2</month><year>2020</year></date></history><permissions><copyright-statement>© The Author(s) 2020</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1" abstract-type="Standfirst"><p id="Par1">The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Vaccines</kwd><kwd>Microbiology</kwd><kwd>Pathogenesis</kwd><kwd>Infection</kwd><kwd>Vaccines</kwd></kwd-group><funding-group><award-group><funding-source><institution>National Key Biosafety Technology Research and Development Program of China (2017YFC1200404-4), Biosafety Research Program of PLA (17SAZ08).</institution></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p id="Par2">An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020). The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China<sup><xref ref-type="bibr" rid="CR1">1</xref></sup>. A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China<sup><xref ref-type="bibr" rid="CR2">2</xref></sup>. COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3.0 days (range, 0 to 24.0), and the time from symptom onset to developing pneumonia is 4.0 days (range, 2.0 to 7.0)<sup><xref ref-type="bibr" rid="CR3">3</xref></sup>. Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role<sup><xref ref-type="bibr" rid="CR3">3</xref></sup>. Fever, dry cough, and fatigue are common symptoms at onset of COVID-19<sup><xref ref-type="bibr" rid="CR4">4</xref></sup>. Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans<sup><xref ref-type="bibr" rid="CR4">4</xref>,<xref ref-type="bibr" rid="CR5">5</xref></sup>. No specific antiviral treatments or vaccines are available because it is a new emerging viral disease. Development of SARS-CoV-2-based vaccines is urgently required.</p><p id="Par3">The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines<sup><xref ref-type="bibr" rid="CR6">6</xref></sup>. The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no. MN908947.3)<sup><xref ref-type="bibr" rid="CR7">7</xref></sup>. Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and β-propiolactone<sup><xref ref-type="bibr" rid="CR8">8</xref></sup>. The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus<sup><xref ref-type="bibr" rid="CR9">9</xref></sup>. Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table <xref rid="Tab1" ref-type="table">1</xref>). Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered.<table-wrap id="Tab1"><label>Table 1</label><caption><p>Advantages and disadvantages of different vaccine strategies.</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Vaccine strategy</th><th>Advantages</th><th>Disadvantages</th><th>References</th></tr></thead><tbody><tr><td>Inactivated virus vaccines</td><td>Easy to prepare; safety; high-titer neutralizing antibodies</td><td>Potential inappropriate for highly immunosuppressed individuals</td><td><sup><xref ref-type="bibr" rid="CR25">25</xref></sup></td></tr><tr><td>Attenuated virus vaccines</td><td>Rapid development; induce high immune responses</td><td>Phenotypic or genotypic reversion possible; can still cause some disease</td><td><sup><xref ref-type="bibr" rid="CR25">25</xref></sup></td></tr><tr><td>Subunit vaccines</td><td>High safety; consistent production; can induce cellular and humoral immune responses; high-titer neutralizing antibodies</td><td>High cost; lower immunogenicity; require repeated doses and adjuvants</td><td><sup><xref ref-type="bibr" rid="CR12">12</xref>,<xref ref-type="bibr" rid="CR14">14</xref></sup></td></tr><tr><td>Viral vector vaccines</td><td>Safety; induces high cellular and humoral immune responses</td><td>Possibly present pre-existing immunity</td><td><sup><xref ref-type="bibr" rid="CR12">12</xref></sup></td></tr><tr><td>DNA vaccines</td><td>Easier to design; high safety; high-titer neutralizing antibodies</td><td>Lower immune responses in humans; repeated doses may cause toxicity</td><td><sup><xref ref-type="bibr" rid="CR23">23</xref></sup></td></tr><tr><td>mRNA vaccines</td><td>Easier to design; high degree of adaptability; induce strong immune responses</td><td>Highly unstable under physiological conditions</td><td><sup><xref ref-type="bibr" rid="CR23">23</xref></sup></td></tr></tbody></table></table-wrap></p><p id="Par4">Accumulated releases of SARS-CoV-2 genomes such as GenBank accession numbers MN908947.3, MN975262.1, NC_045512.2, MN997409.1, MN985325.1, MN988669.1, MN988668.1, MN994468.1, MN994467.1, MN988713.1, and MN938384.1 facilitate the development of virus-based subunit vaccines. SARS-CoV-2, which is similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), is an enveloped, single- and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins<sup><xref ref-type="bibr" rid="CR7">7</xref>,<xref ref-type="bibr" rid="CR10">10</xref></sup>. A mature SARS-CoV-2 has four structural proteins, namely, envelope (E), membrane (M), nucleocapsid (N), and spike (S)<sup><xref ref-type="bibr" rid="CR10">10</xref></sup>. All these proteins may serve as antigens to stimulate neutralizing antibodies and increase CD4<sup>+</sup>/CD8<sup>+</sup> T-cell responses<sup><xref ref-type="bibr" rid="CR8">8</xref>,<xref ref-type="bibr" rid="CR9">9</xref></sup>. However, subunit vaccines require multiple booster shots and suitable adjuvants to work, and certain subunit vaccines such as hepatitis B surface antigen, PreS1, and PreS2 may fail to yield protective response when tested clinically<sup><xref ref-type="bibr" rid="CR11">11</xref></sup>. The DNA and mRNA vaccines that are easier to design and proceed into clinical trials very quickly remain experimental. The viral vector-based vaccines could also be quickly constructed and used without an adjuvant<sup><xref ref-type="bibr" rid="CR12">12</xref></sup>. However, development of such vaccines might not start until antigens containing the neutralizing epitopes are identified<sup><xref ref-type="bibr" rid="CR8">8</xref></sup>.</p><p id="Par5">The E and M proteins have important functions in the viral assembly of a coronavirus, and the N protein is necessary for viral RNA synthesis<sup><xref ref-type="bibr" rid="CR13">13</xref></sup>. Deletion of E protein abrogated the virulence of CoVs, and several studies have explored the potential of recombinant SARS-CoV or MERS-CoV with a mutated E protein as live attenuated vaccines<sup><xref ref-type="bibr" rid="CR13">13</xref>,<xref ref-type="bibr" rid="CR14">14</xref></sup>. The M protein can augment the immune response induced by N protein DNA vaccine against SARS-CoV;<sup><xref ref-type="bibr" rid="CR15">15</xref></sup> however, the conserved N protein across CoV families implies that it is not a suitable candidate for vaccine development, and the antibodies against the N protein of SARS-CoV-2 do not provide immunity to the infection<sup><xref ref-type="bibr" rid="CR16">16</xref></sup>. The critical glycoprotein S of SARS-CoV-2 is responsible for virus binding and entry<sup><xref ref-type="bibr" rid="CR16">16</xref></sup>. The S precursor protein of SARS-CoV-2 can be proteolytically cleaved into S1 (685 aa) and S2 (588 aa) subunits<sup><xref ref-type="bibr" rid="CR10">10</xref></sup>. The S2 protein is well conserved among SARS-CoV-2 viruses and shares 99% identity with that of bat SARS-CoVs<sup><xref ref-type="bibr" rid="CR10">10</xref></sup>. The vaccine design based on the S2 protein may boost the broad-spectrum antiviral effect and is worth testing in animal models. Antibodies against the conserved stem region of influenza hemagglutinin have been found to exhibit broadly cross-reactive immunity, but are less potent in neutralizing influenza A virus<sup><xref ref-type="bibr" rid="CR17">17</xref></sup>. In contrast, the S1 subunit consists of the receptor-binding domain (RBD), which mediates virus entry into sensitive cells through the host angiotensin-converting enzyme 2 (ACE2) receptor<sup><xref ref-type="bibr" rid="CR18">18</xref></sup>. The S1 protein of 2019-nCoV shares about 70% identity with that of human SARS-CoVs. The highest number of variations of amino acids in the RBD is located in the external subdomain, which is responsible for the direct interaction between virus and host receptor<sup><xref ref-type="bibr" rid="CR10">10</xref>,<xref ref-type="bibr" rid="CR18">18</xref></sup>. Blocking the initial entry of a virus is proposed as a successful strategy in controlling viral infection. Based on SARS vaccine development, most vaccine candidates target the S protein, which induces neutralizing antibody responses and stimulates a protective cellular immunity against SARS-CoVs<sup><xref ref-type="bibr" rid="CR12">12</xref></sup>. Bukreyev et al.<sup><xref ref-type="bibr" rid="CR19">19</xref></sup> showed that immunization of African green monkeys with the full-length S protein of SARS-CoV protects monkeys from subsequent homologous SARS-CoV challenge. Administration of SARS-CoV RBD proteins can also induce highly potent neutralizing antibodies and long-term protective immunity in animal models<sup><xref ref-type="bibr" rid="CR20">20</xref></sup>. Thus, the generation of antibodies targeting the S1 subunit of SARS-CoV-2 would be an important preventive and treatment strategy that can be tested further in suitable models before clinical trials<sup><xref ref-type="bibr" rid="CR10">10</xref></sup>.</p><p id="Par6">Vaccine delivery modality and immunization strategy are important issues to be considered for achieving effective antiviral immunity. As a cause of respiratory tract infection and as demonstrated by the findings of SARS-CoV-2 in stools<sup><xref ref-type="bibr" rid="CR1">1</xref>,<xref ref-type="bibr" rid="CR21">21</xref></sup>, administration of vaccines by oral or aerosol routes will induce mucosal immune responses and are possible modes of SARS-CoV-2 vaccine immunization. A safe DNA vector for preparation of DNA vaccines<sup><xref ref-type="bibr" rid="CR22">22</xref></sup>, an attenuated virus strain for design of chimeric viral vaccines<sup><xref ref-type="bibr" rid="CR23">23</xref></sup>, and engineered safe bacteria for production of membrane vesicle-vaccines<sup><xref ref-type="bibr" rid="CR24">24</xref></sup> could be explored for vaccine delivery and are worth investigating in the near future.</p><p id="Par7">We can assume that virus-based vaccines should prove valuable in combatting COVID-19. In addition to the entire virus particle-associated inactivated or attenuated viral vaccines, the subunit candidates, such as S1 protein and/or the RBD element of SARS-CoV-2, are also valuable targets for vaccine design. Combining subunit vaccines with established or new adjuvants such as alum versus modern adjuvants such as the GSK AS series of adjuvants may represent a faster and safer strategy to move through early clinical development with the caveat that the protective efficacy may not be strong enough. As a result, immunizing the subunit vaccines with proper delivery platforms and immunization strategies to enhance the immune responses should be considered. We expect researchers who are racing against time will bring a new SARS-CoV-2-based vaccine from gene sequence to clinical testing in approximately 16–20 weeks.</p></body><back><fn-group><fn><p><bold>Publisher’s note</bold> Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></fn></fn-group><ack><title>Acknowledgements</title><p>This work was supported by the National Key Biosafety Technology Research and Development Program of China (2017YFC1200404-4), and the Biosafety Research Program of PLA (17SAZ08).</p></ack><notes notes-type="author-contribution"><title>Author contributions</title><p>W.S. and Y.R. wrote the manuscript: Y.Y. and X.R. edited the manuscript.</p></notes><notes notes-type="COI-statement"><title>Competing interests</title><p id="Par8">The authors declare no competing interests.</p></notes><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><mixed-citation publication-type="other">Li, Q. et al. 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