Vaccine type Vaccine compound Production system Adjuvant Route Animal model Immune response Side effect Note Reference Humoral cellular protective immunity Protein based S-protein Residues 14-762 Insect cells Saponin: QS21 S.C. Mice ✓ ✓ ✓ N/A The better significant protection obtained with the QS21. [31 ] Ribi: MPL+TDM ✓ ✓ ✓ RBD-Fc (193 aa) Residues 318- 510 Mammalian 293T cells Freund’s complete adjuvant. Boost: Freund’s incomplete adjuvant I.M. Mice ✓ N/A ✓ Only one vaccinated mouse from five had mild alveolar damage in the lung tissues. [17 ] RBD (193 aa) Mammalian 293T cells Sigma adjuvant system S.C. Mice ✓ N/A ✓ N/A [28 ] Residues 318–510 Insect cells ✓ N/A ✓ E. coli ✓ N/A ✓ RBD (193 aa) Residues 318–510 (CHO)-K1 cells Freund’s complete Boost: Freund’s in-complete S.C. Mice ✓ ✓ ✓ N/A Virus replication detected in two of five mice. [70 ] RBD (219 aa) Residues 318–536 (CHO)-K1 cells Freund’s complete Boost: Freund’s in-complete S.C. Mice ✓ ✓ ✓ N/A [66 ] Truncated S-protein Insect cells Protollin I.N. Mice ✓ N/A ✓ No significant histopathology findings Significantly lower virus titers in I.N. route than I.M due to induction of IgA [77 ] Alum I.M. ✓ N/A ✓ SARS-VLPs Insect cells Without adjuvant I.M. Mice ✓ N/A ✓ No weight loss. [59 ] S-protein Residues 1-1196aa + Influenza M1 protein Residues 531-568aa Without adjuvant I.N. ✓ N/A ✓ Minor weight loss (3-4%) Alum I.M. ✓ N/A ✓ No weight loss S-protein Residues 1-1196aa Insect cells Without adjuvant I.M. Mice ✓ N/A ✓ 70% survival 7.5-15% Weight loss [59 ] Without adjuvant I.N. ✓ N/A x Alum I.M. ✓ N/A ✓ No weight loss S-protein Residues 1–1194 Insect cells AuNPs S.C. Mice ✓ N/A ✓ 43% survival Ruffled fur and body weight loss for all groups. Eosinophilic infiltrations in the lungs of both S-protein and S +AuNP immunized mice [63 ] TLR agonists ✓ N/A ✓ Without adjuvant ✓ N/A ✓ 66% survival Viral vector based MVA-S Full length Primary CEF cells Without adjuvant I.M. I.N. Mice ✓ ✓ N/A N/A ✓ ✓ No obvious disease [91 ] MVA-S Full length BHK21 cells Without adjuvant S.C. and I.P. Ferrets ✓ N/A X Enhanced hepatitis in ferrets after SARS-CoV challenge No significant effects on the level of SARS-CoV replication in ferrets. [61 ] MVA-S Full length BHK21 cells Without adjuvant S.C. and I.P. Ferrets ✓ N/A X No enhanced pathology during SARS-CoV infection of liver Presence of virus in all the clinical specimens. [60 ] MVA-N Full length X N/A X Attenuated parainfluenza virus (BHPIV3)-S protein Full length LLC-MK2 cells Without adjuvant I.N. African green monkeys ✓ N/A ✓ No evidence of immune-mediated enhancement of infection or disease [87 ] NDV-BC/S Full-length Embryonated chicken eggs Without adjuvant I.N. and I.T. African green monkeys ✓ ✓ ✓ No evidence of enhanced clinical disease Numbers of blood SARS-CoV specific T-cells was low [90 ] NDV-VF/S Full-length NDV-BC/S1 Residues 1-762 ✓ ✓ ✓ N/A N/A X AAV-RBD (193-aa) HEK293T cells Without adjuvant I.M. Mice ✓ ✓ ✓ No antibody-mediated disease enhancement I.N. vaccination induced much stronger responses than I.M. route but with the same protective immunity effectiveness. [45 ] Residue 318–510 I.N. ✓ ✓ ✓ VSV-S Full length BHK-21 cells Without adjuvant I.N. Mice ✓ N/A ✓ No enhancement of infection [86 ] DNA based pCI-WPRE-S Full length Mammalian 293T cells Without adjuvant I.M. Mice ✓ N/A ✓ N/A [79 ] Plasmid DNA-S Full length Synthetic Human preferred codons Without adjuvant I.M. Mice ✓ ✓ ✓ No enhancement of infection Protection was mediated by a humoral immune mechanism. [78 ]