Review Article

Protective Immunity against SARS Subunit Vaccine Candidates Based on Spike Protein: Lessons for Coronavirus Vaccine Development

Table 1

In vivo immunological responses against SARS-CoV spike-based vaccine candidates.

Vaccine typeVaccine compoundProduction systemAdjuvantRouteAnimal modelImmune responseSide effectNoteReference
Humoralcellularprotective immunity

Protein basedS-protein
Residues
14-762
Insect cellsSaponin: QS21S.C.MiceN/AThe better significant protection obtained with the QS21.[31]
Ribi: MPL+TDM
RBD-Fc
(193 aa)
Residues 318- 510
Mammalian 293T cellsFreund’s complete adjuvant.
Boost: Freund’s incomplete adjuvant
I.M.MiceN/AOnly one vaccinated mouse from five had mild alveolar damage in the lung tissues.[17]
RBD
(193 aa)
Mammalian 293T cellsSigma adjuvant systemS.C.MiceN/AN/A[28]
Residues 318–510Insect cellsN/A
E. coliN/A
RBD (193 aa)
Residues 318–510
(CHO)-K1 cellsFreund’s complete
Boost: Freund’s in-complete
S.C.MiceN/AVirus replication detected in two of five mice.[70]
RBD (219 aa)
Residues 318–536
(CHO)-K1 cellsFreund’s complete
Boost: Freund’s in-complete
S.C.MiceN/A[66]
Truncated S-proteinInsect cellsProtollinI.N.MiceN/ANo significant histopathology findingsSignificantly lower virus titers in I.N. route than I.M due to induction of IgA[77]
AlumI.M.N/A
SARS-VLPsInsect cellsWithout adjuvantI.M.MiceN/ANo weight loss.[59]
S-protein Residues 1-1196aa + Influenza M1 protein Residues 531-568aaWithout adjuvantI.N.N/AMinor weight loss (3-4%)
AlumI.M.N/ANo weight loss
S-protein Residues 1-1196aaInsect cellsWithout adjuvantI.M.MiceN/A
70% survival
7.5-15%
Weight loss
[59]
Without adjuvantI.N.N/Ax
AlumI.M.N/ANo weight loss
S-protein Residues 1–1194Insect cellsAuNPsS.C.MiceN/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 agonistsN/A
Without adjuvantN/A✓ 66% survival

Viral vector basedMVA-S Full lengthPrimary CEF cellsWithout adjuvantI.M.
I.N.
Mice
N/A
N/A

No obvious disease[91]
MVA-S Full lengthBHK21 cellsWithout adjuvantS.C. and I.P.FerretsN/AXEnhanced hepatitis in ferrets after SARS-CoV challengeNo significant effects on the level of SARS-CoV replication in ferrets.[61]
MVA-S Full lengthBHK21 cellsWithout adjuvantS.C. and I.P.FerretsN/AXNo enhanced pathology during SARS-CoV infection of liverPresence of virus in all the clinical specimens.[60]
MVA-N Full lengthXN/AX
Attenuated parainfluenza virus (BHPIV3)-S protein Full lengthLLC-MK2 cellsWithout adjuvantI.N.African green monkeysN/ANo evidence of immune-mediated enhancement of infection or disease[87]
NDV-BC/S Full-lengthEmbryonated chicken eggsWithout adjuvantI.N. and I.T.African green monkeysNo evidence of enhanced clinical diseaseNumbers of blood SARS-CoV specific T-cells was low[90]
NDV-VF/S Full-length
NDV-BC/S1 Residues 1-762
N/AN/AX
AAV-RBD (193-aa)HEK293T cellsWithout adjuvantI.M.MiceNo antibody-mediated disease enhancementI.N. vaccination induced much stronger responses than I.M. route but with the same protective immunity effectiveness.[45]
Residue 318–510I.N.
VSV-S Full lengthBHK-21 cellsWithout adjuvantI.N.MiceN/ANo enhancement of infection[86]

DNA basedpCI-WPRE-S Full lengthMammalian 293T cellsWithout adjuvantI.M.MiceN/AN/A[79]
Plasmid DNA-S Full lengthSynthetic Human preferred codonsWithout adjuvantI.M.MiceNo enhancement of infectionProtection was mediated by a humoral immune mechanism.[78]

Abbreviations: I.M.: intramuscular; I.N.: intranasal; S.C.: subcutaneous; I.P.: intraperitoneal; I.T.: intrathecal; N/A: not available; X: not induced. Survival rate is given under the protective immunity column if it was indicated in the reference article.