Table 2.
Studies on active immunization in SARS
| Type of vaccine | Gene target or antigen | Animal and dosage | Immune response | Protection from SARS CoV challenge? | Reference (ref. no.) |
|---|---|---|---|---|---|
| Inactivated vaccine. Infected Vero E6 cells treated with β-propiolactone and chromatography. | Whole virus | BALB/c mice. 0.1–0.3 μ g intramuscularly 2 doses 3 weeks apart. | Neutralizing antibodies. | Not done | Tang, L. et al. DNA Cell Biol. 2004 (133) |
| UV inactivated whole virion. | Whole virus | BALB/c mice, 10ug with or without alum adjuvant; subcutaneous. 2 doses 7 weeks apart. | Neutralizing antibody and T-cell responses. | Not done | Takasuka, N. et al. Int. Immunol. 2004 (132) |
| Recombinant antigen. Specifically constructed S2 fragments (Leu803 to Ala828 in F3 and Pro1061 to Ser1093 in F9). | Spike protein | Rabbits 0.5–1 mg, BALB/c mice 50–100 μg. Boosted every 2 weeks. | Neutralizing antibodies (in vitro pseudotyped virus assay). | Not done | Zhang, H. et al. J. Virol. 2004 (123) |
| DNA vaccine. Codon-optimized spike protein. | Spike protein | BALB/c mice. 25 μg intramuscularly 3 doses 3 weeks apart. | Specific neutralizing antibodies; T-cell responses (CD4+ and CD8+ T cells against spike protein). | >106 decrease in lung titer; ~102 decrease in nasal titer. Protection mediated by humoral rather than T-cell mechanisms. | Yang, Z.Y. et al. Nature 2004 (126) |
| DNA vaccine. N-linked calreticulin. | Nucleocapsid protein | C57BL/6 mice. DNA-coated gold beads 3 doses 1 week apart. | Antibody and CD8+ T-cell responses against nucleocapsid protein. Protects mice against vaccinia expressing SARS-CoV nucleocapsid. | Not done | Kim, T.W. et al. J. Virol. 2004 (127) |
| DNA vaccine with spike protein. | Spike protein | Balb/c mice. 150 μg intramuscularly 3 doses 3 weeks apart. | Neutralizing antibodies TH1 switch. | Not done | Zeng, F. et al. Biochem. Biophys Res. Commun. 2004 (128) |
| DNA vaccine with nucleocapsid protein. | Nucleocapsid protein | C3H/He mice. 0.05 μg intramuscularly 3 doses 2 weeks apart. | Cytotoxic T cells Nucleocapsid-specific antibodies. | Not done | Zhu, M.S. et al. Immunol. Lett. 2004 (129) |
| Adenoviral vector. Codon-optimized spike, membrane and nucleocapsid proteins. | Separate constructs for spike, membrane, and nucleocapsid proteins | Rhesus macaques. 1011 PFU of all three vectors (spike, membrane and nucleocapsid proteins) intramuscularly 2 doses 4 weeks apart. | Neutralizing antibody response. T-cell responses against nucleocapsid. | Not done | Gao, W. et al. Lancet 2003 (130) |
| Modified vaccinia Ankara (MVA) with spike protein. | Spike protein | BALB/c mice. 107 PFU intramuscularly or intranasally 2 doses 4 weeks apart. | Neutralizing antibodies. | Decreased lung/nasal titer; passive transfer of immune serum confers protection. | Bisht, H. et al. Proc. Natl. Acad Sci. USA 2004 (131) |
| Recombinant attenuated parainfluenza type 3 vector with spike protein. | Spike protein | African green monkeys. One dose of 106 TCID50 intranasally and intratracheally. | Neutralizing antibodies. | Prevents viral shedding. | Bukreyev, A. et al. Lancet 2004 (100) |
| Recombinant parinfluenza virus type 3 vector. | Spike, membrane, envelope and nucleocapsid proteins | Golden Syrian hamsters. 106 TCID50 Single dose, intranasally. | Only spike protein construct induced neutralizing antibody. | Only spike protein vaccine construct induces protection against challenge. | Buchholtz, U.J. et al. Proc. Natl. Acad. Sci. USA 2004 (102) |