1 , 2 , 3 ] Till April 8, 2020, there were over 1?431?973 confirmed cases globally, resulting in at least 82?085 deaths. These SARS\CoV\2 isolates participate in the genus from the Coronaviradae family members which can be an enveloped solitary\stranded RNA disease including a 30?kb genome with 14 open up reading structures including four main viral structure protein: spike (S), membrane (M), envelope (E), and nucleocapsid (N) protein.[ 4 , 5 , 6 , 7 ] The S gene sequences of SARS\CoV\2 isolates possess a 93.1% nucleotide series identity towards the bat coronavirus RaTG13, but only significantly less than 75% nucleotide series identity towards the severe acute respiratory symptoms coronavirus (SARS\CoV). The viral S sequences of SARS\CoV\2 in comparison to SARS\CoV possess three additional brief insertions in the N\terminal site, and four out of five crucial residues adjustments in the receptor\binding theme of S proteins receptor binding site (RBD).[ 6 , 7 ] Although both SARS\CoV and SARS\CoV\2 talk about the same human being mobile receptor\angiotensin switching enzyme II, SARS\CoV\2 is apparently more transmitted from human being to human being readily.[ 1 , 8 , 9 ] The S protein may be the major target for COVID\19 vaccine advancement, mainly predicated on the elicitation of virus neutralizing antibodies as the immune correlates to vaccine protection. The existing position of COVID\19 vaccine advancement contains, i) three stage I vaccine applicants, ii) 11 preclinical vaccine applicants, and iii) 26 study\stage vaccine applicants (Desk?1; [https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker?feed=Regulatory-Focus?utm_source=Facebook&utm_medium=social&utm_campaign=Regulatory-Focus]). Most of these vaccine candidates are based on the S antigen either as inactivated vaccines, subunit vaccines, viral vectored vaccines, and nucleic acid\based DNA or mRNA vaccines. Among these vaccine candidates, the Coalition for Epidemic Preparedness Innovations (CEPI) has provided funding to develop COVID\19 vaccines using the following platform technology: a) Curevac Inc. (mRNA), b) Inovio Pharmaceuticals Inc. (DNA), c) Moderna, Inc. (mRNA), d) University of Queensland (molecular clam), e) Novavax (nanoparticles), f) University of Oxford (adenovirus vector), g) University of Hong Kong (live\attenuated influenza virus), and h) Institute of Pasteur (measles vector) to accelerate the development of vaccines and enable equitable access to these vaccines for people during outbreaks [https://cepi.net/covid-19/]. Table 1 The current status of COVID\19 vaccine development thead th align=”left” rowspan=”1″ colspan=”1″ Company /th th align=”left” rowspan=”1″ colspan=”1″ Vaccine candidates /th th align=”left” rowspan=”1″ colspan=”1″ Status /th /thead ModernamRNA\1273 Phase I “type”:”clinical-trial”,”attrs”:”text”:”NCT04283461″,”term_id”:”NCT04283461″NCT04283461 CanSino BiologicsAd5\nCoV Phase I ChiCTR2000030906 InovioINO\4800 (DNA) Phase I “type”:”clinical-trial”,”attrs”:”text”:”NCT04336410″,”term_id”:”NCT04336410″NCT04336410 Pfizer and BioNTechBNT162 (mRNA)Pre\clinicalNovavaxRecombinant nanoparticle vaccinePre\clinicalCureVacmRNA\based vaccinePre\clinicalGenerexIi\Key peptide vaccinePre\clinicalVaxartOral recombinant vaccinePre\clinicalImperial College LondonSelf\amplifying RNA vaccinePre\clinicalMedicagoPlant\based vaccine (VLP)Pre\clinicalTakis BiotechDNA\based vaccinePre\clinicalJ&J and BARDAAdVac and PER.C6 systemsPre\clinicalAltimmuneIntranasal vaccinePre\clinicalUniversity of SaskatchewanNot revealedPre\clinicalClover and GSKS\TrimerResearchHeat Biologicsgp96\based vaccineResearchCSL and University of QueenslandMolecular clamp vaccineResearchSanofiNot revealedResearchiBioPlant\based vaccineResearchExpreS2ion BiotechnologiesNot revealedResearchEpiVaxIi\Key peptide vaccineResearchCodagenixLive attenuated vaccineResearchZydus CadilaDNA and/or live attenuated recombinant vaccine candidateResearchSinovacFormalin\inactivated and alum\adjuvanted applicant vaccineResearchGeovax and BravovaxModified Vaccinia Ankara pathogen like contaminants (MVA\VLP) vaccineResearchUniversity of OxfordChimpanzee adenovirus vaccine vector (ChAdOx1)ResearchGreffexAdenovirus\based vector vaccineResearchWalter Reed and USAMARIIDNot revealedResearchMIGALModified avian coronavirus vaccineResearchVaxil BioProtein subunit COVID\19 vaccine candidateResearchAJVaccinesNot revealedResearchBaylor Re\purposed SARS vaccine; S1 or RBD proteins vaccine ResearchInstitut PasteurNot revealedResearchTonix Pharmaceuticals and Southern ResearchHorsepox vaccine with percutaneous administrationResearchFudan College or university, Shanghai Jiao Tong College or university, and RNACure BiopharmamRNA\based vaccineResearchArcturus Therapeutics and Duke\NUSSelf\replicating RNA and nanoparticle non\viral delivery systemResearchUniversity of PittsburghNot revealedResearchImmunoPreciseNot revealedResearchPeter Doherty Institute for Infections and ImmunityNot revealedResearchTulane UniversityNot revealedResearch Open in another window This article has been made freely available through PubMed Central within the COVID-19 public health AM966 emergency response. It could be useful for unrestricted analysis re-use and evaluation in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. To date, many previous studies of SARS\CoV, Middle East respiratory syndrome\related coronavirus (MERS\CoV), and other coronavirus vaccines revealed several safety concerns associated with the use of coronavirus S\based vaccines, including inflammatory and immunopathological effects such as pulmonary eosinophilic infiltration and antibody\dependent disease enhancement (ADE) following subsequent viral problem of vaccinated pets.[ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ] The anti\S antibodies for ADE might facilitate uptake by macrophage expressing FcR, resulting in macrophage stimulation as well as the creation of proinflammatory cytokines (IL\6, IL\8, and MCP1) and lack of tissue\fixed cytokine (TGF).[ 22 ] Furthermore, the Th2\linked immunopathology continues to be noted for the inactivated vaccines of respiratory syncytial pathogen after viral problem[ 23 , 24 , 25 ] as well as the inactivated vaccines of MERS\CoV after pathogen challenge.[ 20 ] Thus, the security and the potentially harmful responses in vaccines to develop ADE antibodies against any coronaviruses should be carefully assessed in human trials.[ 26 ] It has been proposed that this neutralizing epitope\rich S1 region, or the RBD region, instead of the entire full\size S protein as an alternative target for MERS\CoV vaccine development.[ 27 ] If the usage of RBD or S1 antigen of SARS\CoV\2, or selecting Th1\skewed adjuvants than alum adjuvant rather, can stay away from the inflammatory, immunopathological, and ADE results, requires further research from animal versions and human studies. These findings are essential for creating a effective and safe COVID\19 vaccine particularly. Suh\Chin Wu Conflict appealing The writer declares no conflict appealing. Acknowledgements This ongoing work was supported with the Ministry of Science and Technology, Taiwan (MOST108\2321\B\007\001, MOST108\2321\B\002\006), and National Tsing Hua University (109R2807E1). Notes Wu S., Idea and Improvement for COVID\19 Vaccine Advancement. Biotechnol. J. 2020, 2000147 10.1002/biot.202000147 [CrossRef]. SARS\CoV possess three additional brief insertions in the N\terminal domains, and four out of five essential residues adjustments in the receptor\binding theme of S proteins receptor binding domains (RBD).6 [ , 7 ] Although both SARS\CoV and SARS\CoV\2 talk about the same individual mobile receptor\angiotensin changing enzyme II, SARS\CoV\2 is apparently more readily transmitted from human being to human being.[ 1 , 8 , 9 ] The S protein is the major target for COVID\19 vaccine development, mainly based on the elicitation of disease neutralizing antibodies as the immune correlates to vaccine safety. The current status of COVID\19 vaccine development includes, i) three phase I vaccine candidates, ii) 11 preclinical vaccine candidates, and iii) 26 study\stage vaccine candidates (Table?1; [https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker?feed=Regulatory-Focus?utm_source=Facebook&utm_medium=social&utm_campaign=Regulatory-Focus]). Most of these vaccine candidates are based on the S antigen either as inactivated vaccines, subunit vaccines, viral vectored vaccines, and nucleic acid\centered AM966 DNA or mRNA vaccines. Among these vaccine candidates, the Coalition for Epidemic Preparedness Improvements (CEPI) has offered funding to develop COVID\19 vaccines using the following platform technology: a) Curevac Inc. (mRNA), b) Inovio Pharmaceuticals Inc. (DNA), c) Moderna, Inc. (mRNA), d) University or college of Queensland (molecular clam), e) Novavax (nanoparticles), f) College or university of Oxford (adenovirus vector), g) College or university of Hong Kong (live\attenuated influenza virus), and h) Institute of Pasteur (measles vector) to accelerate the development of vaccines and enable equitable access to these vaccines for people during outbreaks [https://cepi.net/covid-19/]. Table 1 The current status of COVID\19 vaccine advancement thead th align=”remaining” rowspan=”1″ colspan=”1″ Business /th th align=”left” rowspan=”1″ colspan=”1″ Vaccine candidates /th th align=”left” rowspan=”1″ colspan=”1″ Status /th /thead ModernamRNA\1273 Phase I “type”:”clinical-trial”,”attrs”:”text”:”NCT04283461″,”term_id”:”NCT04283461″NCT04283461 CanSino BiologicsAd5\nCoV Phase I ChiCTR2000030906 InovioINO\4800 (DNA) Phase I “type”:”clinical-trial”,”attrs”:”text”:”NCT04336410″,”term_id”:”NCT04336410″NCT04336410 Pfizer and BioNTechBNT162 (mRNA)Pre\clinicalNovavaxRecombinant nanoparticle vaccinePre\clinicalCureVacmRNA\based vaccinePre\clinicalGenerexIi\Key peptide vaccinePre\clinicalVaxartOral recombinant vaccinePre\clinicalImperial College LondonSelf\amplifying RNA vaccinePre\clinicalMedicagoPlant\based vaccine (VLP)Pre\clinicalTakis BiotechDNA\based vaccinePre\clinicalJ&J and BARDAAdVac and PER.C6 systemsPre\clinicalAltimmuneIntranasal vaccinePre\clinicalUniversity of SaskatchewanNot revealedPre\clinicalClover and GSKS\TrimerResearchHeat Biologicsgp96\based vaccineResearchCSL and University of QueenslandMolecular clamp vaccineResearchSanofiNot revealedResearchiBioPlant\based vaccineResearchExpreS2ion BiotechnologiesNot revealedResearchEpiVaxIi\Key peptide vaccineResearchCodagenixLive attenuated vaccineResearchZydus CadilaDNA and/or live attenuated recombinant vaccine candidateResearchSinovacFormalin\inactivated and alum\adjuvanted candidate vaccineResearchGeovax and BravovaxModified Vaccinia Ankara pathogen like contaminants (MVA\VLP) vaccineResearchUniversity of OxfordChimpanzee adenovirus vaccine vector (ChAdOx1)ResearchGreffexAdenovirus\based vector vaccineResearchWalter Reed and USAMARIIDNot revealedResearchMIGALModified avian coronavirus vaccineResearchVaxil BioProtein subunit COVID\19 vaccine candidateResearchAJVaccinesNot revealedResearchBaylor Re\purposed SARS vaccine; S1 or RBD proteins vaccine ResearchInstitut PasteurNot revealedResearchTonix Pharmaceuticals and Southern ResearchHorsepox vaccine with percutaneous administrationResearchFudan College or university, Shanghai Jiao Tong College or university, and RNACure BiopharmamRNA\centered vaccineResearchArcturus Therapeutics and Duke\NUSSelf\replicating RNA and nanoparticle non\viral delivery systemResearchUniversity of PittsburghNot revealedResearchImmunoPreciseNot revealedResearchPeter Doherty Institute for Disease and ImmunityNot revealedResearchTulane UniversityNot revealedResearch Open up in another window This informative article is being produced FRAP2 freely obtainable through PubMed Central within the COVID-19 general public wellness emergency response. It could be useful for unrestricted study re-use and evaluation in any type or at all with acknowledgement of the initial source, throughout the public wellness emergency. To day, many previous research of SARS\CoV, Middle East respiratory system symptoms\related coronavirus (MERS\CoV), and additional coronavirus vaccines exposed several safety concerns associated with the use of coronavirus S\based vaccines, including inflammatory and immunopathological effects such as pulmonary eosinophilic infiltration and antibody\dependent disease enhancement (ADE) following subsequent viral challenge of vaccinated animals.[ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ] The anti\S antibodies for ADE may facilitate uptake by macrophage expressing FcR, leading to macrophage stimulation and the production of proinflammatory cytokines (IL\6, IL\8, and MCP1) and loss of tissue\repaired cytokine (TGF).[ 22 ] Moreover, the Th2\associated immunopathology has been documented for the inactivated vaccines of respiratory syncytial virus after viral challenge[ 23 , 24 , 25 ] and the inactivated vaccines of MERS\CoV after virus challenge.[ 20 ] Thus, the safety and the potentially harmful responses in vaccines to develop ADE antibodies against any coronaviruses ought to be thoroughly assessed in individual studies.[ 26 ] It’s been proposed the fact that neutralizing epitope\wealthy S1 area, or the RBD area, rather than the whole full\duration S protein as an alternative target for MERS\CoV vaccine development.[ 27 ] Whether the use of S1 or RBD antigen of SARS\CoV\2, or the selection of Th1\skewed adjuvants rather than alum adjuvant, can steer AM966 clear of the inflammatory, immunopathological, and ADE effects, requires further studies from animal models and human trials. These findings are particularly important for developing a safe and.