For SARS-CoV-1 and MERS-CoV, animal studies and phase I clinical trials of potential vaccines targeting the S protein had encouraging results, with evidence of nAb induction and induction of cellular immunity (Lin et al., 2007, Martin et al., 2008, Modjarrad et al., 2019). These findings are being translated into SARS-CoV-2 vaccine development efforts, hastening the progress drastically. The WHO provided a report in April that reported 63 vaccine candidates in preclinical testing and three in clinical testing (World Health Organization, 2020b). A recent search on May 1, 2020 on ClinicalTrials.gov revealed 10 registered vaccine candidates (Table 5 ). The University of Pittsburgh is also looking to move their microneedle array vaccine candidate containing a codon-optimized S1 subunit protein into clinical trials (Kim et al., 2020). Sanofi and GlaxoSmithKline (GSK) have recently reported their intent to collaborate and bring together Sanofi’s baculovirus expression system, which is used to produce the influenza virus vaccine, Flublok, to create an S protein vaccine adjuvanted with GSK’s AS03. Sinovac Biotech will also enter testing in a clinical trial in China after it was found to protect rhesus macaques from viral challenge without signs of detectable immunopathology (Gao et al., 2020c). Although some of these vaccine candidates are based on platforms that have been used or tested for other purposes, there remain questions regarding their safety and immunogenicity, including the longevity of any induced responses, that will require continual evaluation.
Table 5 Vaccine Candidates Currently Registered for Clinical Trials
Candidate Design Developer Similar Strategy ClinicalTrials.gov Identifier
mRNA-1273 LNP-encapsulated mRNA for full-length S protein ModernaTX CMV (John et al., 2018), ZKV (Pardi et al., 2017) NCT04283461
BNT162a1, b1, b2, c2 LNP-encapsulated mRNA vaccines with different formats of RNA and targets, two for larger S sequence and two for optimized RBD BioNTech SE and Pfizer NCT04368728
INO-4800 DNA vaccine for full-length S protein Inovio Pharmaceuticals MERS-CoV (Modjarrad et al., 2019), HPV (Trimble et al., 2015) NCT04336410
Ad5-nCoV adenovirus type 5 encoding full-length S protein CanSino Biologics EBV (Zhu et al., 2015, Zhu et al., 2017) NCT04313127 (phase I)NCT04341389 (phase II)
ChAdOx1 nCoV-19 adenovirus encoding full-length S protein University of Oxford MERS-CoV (Alharbi et al., 2017), IAV (Antrobus et al., 2014) NCT04324606
COVID-19 LV-SMENP-DC dendritic cells infected with lentivirus expressing SMENP minigenes to express COVID-19 antigens, together with activated CTLs Shenzhen Geno-Immune Medical Institute NCT04276896
COVID-19 aAPCs aAPCs infected with lentivirus expressing minigenes to express COVID-19 antigens Shenzhen Geno-Immune Medical Institute NCT04299724
bacTRL-Spike-1 live bacteria delivering plasmid encoding S protein Symvivo Corporation therapeutics reviewed (Charbonneau et al., 2020) NCT04334980
PiCoVacc inactivated SARS-CoV-2 vaccine Sinovac Biotech HAV, IAV, IBV, poliovirus, rabies virus NCT04352608
SARS-CoV-2 rS spike protein nanoparticle vaccine with or without Matrix-M adjuvant Novavax NCT04368988
aAPCs, artificial antigen-presenting cells; CMV, cytomegalovirus; EBV, Ebola virus; HAV, hepatitis A virus; HPV, human papillomavirus; IAV, influenza A virus; IBV, influenza B virus; LPN, lipid nanoparticle; ZKV, Zika virus.