SARS-CoV 694009 Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation and immune and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses (Wiki: SARS). Severe Acute Respiratory Syndrome (SARS) Passive immunization has been successful in establishing protection from SARS-CoV suggesting an important role for neutralizing antibodies (Wiki: SARS). SARS-CoV has been isolated from humans, civet cats, raccoon dogs, swine and bats, suggesting that several animal species may function as natural reservoirs for future outbreaks. The Chinese horseshoe bat, which is abundant across Southeast Asia, is probably the natural reservoir for SARS-CoV. Ciliated airway epithelium models derived from tracheobronchial airway epithelium of Balb-c mice (MAE), Golden Syrian hamsters (HmAE), and rhesus macaques (RhMAE) have been successfully developed (Sims et al., 2008). Severe acute respiratory syndrome (SARS; pronounced /ˈsɑrz/ sarz) is a respiratory disease in humans which is caused by the SARS coronavirus (SARS-CoV). There has been one near pandemic to date, between the months of November 2002 and July 2003, with 8,096 known infected cases and 774 confirmed human deaths (a case-fatality rate of 9.6%) worldwide being listed in the World Health Organization's (WHO) 21 April 2004 concluding report. Within a matter of weeks in early 2003, SARS spread from the Guangdong province of China to rapidly infect individuals in some 37 countries around the world (Wiki: SARS). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 ADS-MVA vaccine VO_0005110 Recombinant vector vaccine Research live-attenuated modified vaccinia virus Ankara (MVA) [Ref5109:Chen et al., 2005] Intramuscular injection (i.m.) Recombinant live-attenuated modified vaccinia virus Ankara (MVA) had full-length SARS-CoV envelope Spike (S) glycoprotein gene was introduced into the deletion III region of the MVA genome. (Chen et al., 2005) Intramuscular injection (i.m.) S protein(Chen et al., 2005) Recombinant vector construction testing hosts generated high levels of neutralizing antibodies after 2 vaccinations (Chen et al., 2005) immunized intramuscular injection twice with a 4-week interval. 1 × 10^8 TCID50 for the first immunization and a dose of 3 × 10^8 TCID50 for the second injection. (Chen et al., 2005) likely protected (Chen et al., 2005) immunized on days 0 and 28 via intranasal injection before challenged after second immunization on day 28 with 10^5 TCID50 of pathogenic SATS-CoVPUMC01. (Chen et al., 2005) After virus challenge, SARS-CoV shedding detected by RT-PCR was only detected in the nasopharyngeal specimens of one of the four ADS-MVA immunized animals (Rh0413) on day 2 after virus challenge. No virus shedding was detectable on days 4 and 6 postchallenge in these four macaques. SARS-CoV could not be isolated from the lung specimens of ADS-MVA-immunized macaques on day 7 postchallenge. (Chen et al., 2005) testing hosts generated high levels of neutralizing antibodies (Chen et al., 2005) Balb/c (Chen et al., 2005) immunized intramuscular injection twice with a 3-week interval. Two mice were given 2 × 106 TCID50 of the vaccine, and six mice received 2 × 10^7 TCID50.(Chen et al., 2005) testing hosts generated high levels of neutralizing antibodies (Chen et al., 2005) immunized intramuscular injection twice with a 3-week interval (Chen et al., 2005) Neutralizing activity was detected in sera along with a corresponding immunoglobin G titer collected from all three ferrets 7 days after booster immunization with rMVA-S virus, while the titer declined to undetectable level 14 days after the booster (Weingartl et al., 2004). Each ferret was immunized with rMVA-S (ferrets 7 to 9), n day 0 with a dose of 1e8 PFU of the corresponding virus per ferret by intraperitoneal and subcutaneous routes, and a booster immunization was given on day 14 with the same regimen.(Weingartl et al., 2004) Ferrets immunized with rMVA-S (particularly ferret 9) developed severe periportal and panlobular mononuclear hepatitis in contrast to only mild periportal mononuclear hepatitis was observed in control ferrets (Weingartl et al., 2004) . Ferrets were challenged with 1e6 PFU of the SARS-CoV Tor2 isolate by the intranasal route(Weingartl et al., 2004). Study shows correlation with liver damage but does not definitely proof it is caused as SARS-CoV in ferrets also damage liver.(Weingartl et al., 2004) Double Inactivated whole SARS-CoV vaccine VO_0005125 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Inactivated whole virus by formalin and Ultraviolet radiation, hence Double Inactivated (DI) Vaccine (Tseng et al., 2012) Intramuscular injection (i.m.) whole virus (Tseng et al., 2012) Increased titer of neutralizing antibodies and reduced viral titer (Tseng et al., 2012) Balb/c and C57BL/6 (Tseng et al., 2012) Each mouse received 100 µl injection of each vaccine intramuscularly on days 0 and 28. The injection was done at 1 µg, 0.5 µg, 0.25 µg, 0.125 µg of the vaccine (Tseng et al., 2012) protected (Tseng et al., 2012) Eosinophil infiltration in the lung lesions after challenge, type-2 hypersensitivity reaction (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 106TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) Double Inactivated whole SARS-CoV vaccine + alum Inactivated or "killed" vaccine Research Intramuscular injection (i.m.) Inactivated whole virus by formalin and Ultraviolet radiation with alum vaccine (Tseng et al., 2012) alum (Tseng et al., 2012) Intramuscular injection (i.m.) whole virus(Tseng et al., 2012) Increased titer of neutralizing antibodies and reduced viral titer that are higher than without adjuvant, neutrophil + eosinophil infiltration, Th2-type hypersensitivity reaction. (Tseng et al., 2012) BALB/c (Tseng et al., 2012) Each mouse received 100 µl injection of each vaccine intramuscularly on days 0 and 28. The injection was done at 1 µg, 0.5 µg, 0.25 µg, 0.125 µg of the vaccine (Tseng et al., 2012) protected (Tseng et al., 2012) eosinophil infiltration in the lung lesions after challenge, lower than without adjuvant (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 106TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) β-propiolactone-inactivated SARS-CoV vaccine VO_0005114 Inactivated or "killed" vaccine Research subcutaneous injection whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine (See et al., 2006) subcutaneous injection whole virus (See et al., 2006) A 19-fold difference (P=0·02) in total SARS-CoV-specific IgG levels and lung viral titers were reduced by 4 logs to undetectable levels compared with titers observed in the PBS control on day 3 post-challenge, vaccinated animals showed significantly higher levels (P=0·002) of IFN-γ than control animals (See et al., 2006). 129S6/SvEv Vaccination at 0 weeks and 4 weeks (See et al., 2006) Vaccination at 0 weeks and 4 weeks challenged by SARS-CoV-Tor2 at week 7 (See et al., 2006) licensed Severe acute respiratory syndrome human vaccine Generic Unknown VO_0012183 Inactivated or "killed" vaccine Licensed A generic representation of vaccines developed to prevent Severe Acute Respiratory Syndrome (SARS) in humans, primarily utilizing inactivated or 'killed' SARS coronavirus particles to elicit an immune response. These vaccines are designed to provide immunity without causing disease. MA-ExoN vaccine VO_0005108 Live, attenuated vaccine Research intranasal immunization Live-attenuated RNA virus vaccine with engineered inactivation of SARS-CoV ExoN activity (MA-ExoN) (Graham et al., 2012) intranasal immunization MA-ExoN (Graham et al., 2012) generated high levels of neutralizing antibodies (Graham et al., 2012) Balb/c(Graham et al., 2012) intranasally with varying doses (10^2–10^4 PFU, depending on the experiment) of SARS-CoV MA-ExoN (Graham et al., 2012) complete protection (Graham et al., 2012) intranasally injected 1e2.5 vaccination PFU of vaccine of SARS-CoV MA-ExoN then given SARS-CoV once recovered (Graham et al., 2012) MVA/S vaccine VO_0005113 Recombinant vector vaccine Research highly attenuated modified vaccinia virus Ankara [Ref5110:Bisht et al., 2004] Intramuscular injection (i.m.) Recombinant form of the highly attenuated modified vaccinia virus Ankara (MVA) containing the gene encoding full-length SARS-CoV S (Bisht et al., 2004) Intramuscular injection (i.m.) S protein (Bisht et al., 2004) Recombinant vector construction Antibodies neturalized SARS-CoV in vitro after 2 doses (Bisht et al., 2004) Balb/c(Bisht et al., 2004) Mice were inoculated i.n. or i.m. with 10^7 pfu of MVA/S at time 0 and again at 4 weeks. (Bisht et al., 2004) little to no replication of SARS-CoV in the respiratory tracts after internasal inoculation(Bisht et al., 2004) inoculated intranasally or intramuscularly with 7log pfu of MVA at 0 and 4 weeks then challenged with TCID50 of SARS-CoV (Bisht et al., 2004) NDV-BC/S vaccine VO_0005147 Recombinant vector vaccine Research Newcastle disease virus Beaudette C strain (NDV-BC) [Ref5413:DiNapoli et al., 2007] intranasal immunization intranasal immunization Full-length 1,255-aa SARS-CoV S protein (DiNapoli et al., 2007) Induced neutralizing antibodies, Produced S-specific antibodies, Increase in CD8+ T cells creating IFN-γ and TNF-α1 (DiNapoli et al., 2007) African Green Monkey Monkeys were vaccinated with 10^7 pfu of the recombinant virus days 0 and 28 (the two-dose groups) or on day 0 only (the one-dose group). (DiNapoli et al., 2007) Protected (DiNapoli et al., 2007) 28 days after the second dose, they were challenged by the i.n. and i.t. routes with SARS-CoV at a tissue culture 50% infectious dose (TCID50) of 10^6 per site. (DiNapoli et al., 2007) Exhibited average reductions in viral titer of 13-fold, 276-fold, and 1,102-fold in the nasal turbinate, trachea, and lung, respectively. (DiNapoli et al., 2007) NDV-VF/S vaccine VO_0005148 Recombinant vector vaccine Research Lentogenic LaSota strain modified that cleavage sequence of F protein replaced with NDV-BC. [Ref5413:DiNapoli et al., 2007] intranasal immunization intranasal immunization Full-length 1,255-aa SARS-CoV S protein (DiNapoli et al., 2007) Induced neutralizing antibodies, Produced S-specific antubodies, Increase in CD8+ T cells creating IFN-γ and TNF-α1 (DiNapoli et al., 2007) African Green Monkey Monkeys were vaccinated with 107 pfu of the recombinant virus days 0 and 28 (the two-dose groups) or on day 0 only (the one-dose group). (DiNapoli et al., 2007) Protected (DiNapoli et al., 2007) 28 days after the second dose, they were challenged by the i.n. and i.t. routes with SARS-CoV at a tissue culture 50% infectious dose (TCID50) of 10^6 per site. (DiNapoli et al., 2007) Immunization with NDV-VF/S resulted in a 5-fold and 61-fold reduction in nasal turbinate and tracheal SARS-CoV titers, respectively, compared with the control animals. (DiNapoli et al., 2007) RBD-rAAV-SARS-CoV VO_0004678 Recombinant vector vaccine Research Intramuscular injection (i.m.) Inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant (Zheng et al., 2008). Intramuscular injection (i.m.) Induced production of IgG and IgA that exhibited neutralizing activity. Induced a markedly higher level of antigen specific IL-2+ T cells but a slightly lower level of IFN-γ+ T cells in the spleen, IFN-γ-producing CD3+/CD8+ T cells were significantly higher in the splenocytes of RBD-rAAV intranasally versus intramuscularly vaccinated mice. (Zheng et al., 2008) Intranasal vaccination with RBD-rAAV (Zheng et al., 2008). VO_0000287 RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses (Zheng et al., 2008). Mice were challenged with 10^5 TCID50f SARS-CoV strain GZ50 (Zheng et al., 2008). RBD-rAAV-SARS-CoV-version-02 VO_0004679 Recombinant vector vaccine Research Intramuscular injection (i.m.) RBD-rAAV prime/RBD-specific T cell peptide boost (Du et al., 2008). Intramuscular injection (i.m.) Induced high level of IgG Ab response, reaching a peak 3 months post-vaccination, plateaued for 3 months, then decreased. Mucosal IgA Ab peaked 1 month after vaccination, then decreased in the next 5 months. Vaccination induced high levels of Agspecific IL-2+ T cells but slightly lower levels of IFN-γ+ T cells in the spleen. Single dose did not trigger significant IL-2+ and IFN-γ+ T cell response. (Du et al., 2008) Balb/c (Du et al., 2008) Mice were separated into 4 groups (9 mice per group) and primed with RBD-rAAV [intramuscular (i.m.), 2 × 10^11 VP /200 μl)] or RBD-peptides (N50 and N60, 50 μg each) plus CpG ODN (25 μg) [subcutaneous, (s.c.)] or blank AAV, and boosted with RBD-rAAV or RBD-Pep or AAV, respectively (Du et al., 2008). VO_0003057 Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone (Du et al., 2008). Forty days post-vaccination, mice were anaesthetized with isoflurane and i.n. inoculated with 50 μl of SARS-CoV strain GZ50 (5 × 10^5 TCID50) (Du et al., 2008). rDNA-expressed S protein + alum vaccine VO_0005149 DNA vaccine Research intranasal immunization rDNA-expressed ectodomain of the S protein + alum vaccine (Tseng et al., 2012) alum(Tseng et al., 2012) intranasal immunization ectodomain of the S protein(Tseng et al., 2012) Increased titer of neutralizing antibodies and reduced viral titer, higher titer of neutralizing antibodies without adjuvant (Tseng et al., 2012) BALB/c Each mouse received 100 µl injection of the vaccine intramuscularly on days 0 and 28. This was done at 2 µg, 1 µg, 0.5 µg, 0.5 µg of the vaccine per injection (Tseng et al., 2012) protected(Tseng et al., 2012) eosinophil infiltration in the lung lesions after challenge, lessened compared to without adjuvant (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 10^6TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) rDNA-expressed S protein vaccine VO_0005126 DNA vaccine Research Intramuscular injection (i.m.) rDNA-expressed ectodomain of the S protein vaccine Intramuscular injection (i.m.) ecto-domain of S protein (Tseng et al., 2012) Increased titer of neutralizing antibodies and reduced viral titer (Tseng et al., 2012) BALB/c Each mouse received 100 µl injection of the vaccine intramuscularly on days 0 and 28. This was done at 2 µg, 1 µg, 0.5 µg, 0.5 µg of the vaccine per injection (Tseng et al., 2012) protected (Tseng et al., 2012) eosinophil infiltration in the lung lesions after challenge (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 106TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) Recombinant spike polypeptide vaccine VO_0005104 Recombinant vector vaccine Research Intraperitoneal injection (i.p.) intraperitoneal recombinant spike polypeptide generated by amplify gene encoding amino acids residues 14-667 of S protein that was cloned BamHI and KpnI sites of vector pQE-31 that was generated by Escherichia coli (Woo et al., 2005) Intraperitoneal injection (i.p.) S protein (Woo et al., 2005) Recombinant protein preparation No neutralizing antibody production, high IgG levels, lymphocyte proliferation, production of IFN-γ >6000 pg/ml at 48hrs and 72hrs, detectable production of IL-4 at 24hrs (Woo et al., 2005) Balb/c (H-2d) 50 μg administered via intraperitoneal route on days 0, 14, and 28. (Woo et al., 2005) rMA15-ΔE vaccine VO_0005109 Live, attenuated vaccine Research intranasal immunization recombinant MA15 virulent mouse-adapted SARS-CoV (MA15) background of E-deleted vaccine candidate (rMA15-ΔE) (Fett et al., 2013) intranasal immunization virulent mouse-adapted SARS-CoV with E-deletion (rMA15-ΔE) (Fett et al., 2013) Gene mutation Induced neutralizing antibodies, Produced optimal levels of CD4 and CD8 T cells (Fett et al., 2013) Balb/c Protected (Fett et al., 2013) Minor peribronchial and perivascular infiltration in aged (18-month-old) mice (Fett et al., 2013) Mice were challenged with 10^5 PFU of MA15 at day 21 after immunization. (Fett et al., 2013) rMV-S + rMV-N vaccine VO_0005150 Mixed vaccine of two viral vector vaccines Research Live-attenuated recombinant measles virus (rMV) [Ref5398:Liniger et al., 2008]. Intraperitoneal injection (i.p.) Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised spike glycoprotein (S) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) (Weingartl et al., 2004). Intraperitoneal injection (i.p.) codon-optimised spike glycoprotein (S), SARS-CoV nucleocapsid protein (N) (Liniger et al., 2008) Induction of both humoral neutralizing and cellular responses against SARS-CoV, and neutralizing immunity against MV. (Liniger et al., 2008) Ifnartm-CD46Ge transgenic mice(Liniger et al., 2008) Mice were immunized with 0.5 × 10^4 pfu of each recombinant virus per mouse (Liniger et al., 2008) rMV-SARS-CoV-S/Ssol VO_0004711 Recombinant vector vaccine Research Intramuscular injection (i.m.) Live attenuated recombinant measles vaccine (MV) candidates expressing either the membrane-anchored SARS-CoV spike (S) protein or its secreted soluble ectodomain (Ssol) (Escriou et al., 2014). Intramuscular injection (i.m.) Recombinant vector construction A live attenuated recombinant meas(Escriou et al., 2014)s vaccine (MV) candidates expressing either the membrane-anchore SARS-CoV spike (S) protein (Escriou et al., 2014). Production of anti-SARS IgG (specifically IgG2a) after 1 dose, increased by 10-20 fold after second dose. Induced production of neutralizing antibodies, as well as moderate levels of anti-SARS IgA antibodies (Escriou et al., 2014) CD46-IFNAR (Escriou et al., 2014) Mice were immunized with two intraperitoneal (i.p.) injections at 4-week interval of 10^5 TCID50 of MV-S or MV-Ssol recombinant viruses (Escriou et al., 2014). VO_0003057 Recombinant MV expressing the anchored full-length S induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV (Escriou et al., 2014). Mice were inoculated intranasally with 105 pfu of SARS-CoV five weeks after the second immunization (Escriou et al., 2014). SARS Subunit Spike Protein with subunit boosting Vaccine VO_0011486 Recombinant vector vaccine Research Adeno-associated virus [Ref1380:Du et al., 2008]. Subcutaneous injection Subcutaneous injection Recombinant vector construction Vaccination increased production (P < 0.05) of IL-4-producting Th2 cells higher than those in RBD-rAAV prime/RBD-rAAV vaccinated animals, but a lower level (P < 0.05) of IL-10-secreting Th2 cells that play roles in down-regulation of immune responses, as compared to those of RBD-rAAV prime/RBD-rAAV boost vaccination. RBD-rAAV prime/RBD-pep exhibited similar frequencies of IFN-γ-producing cells (Th1) to RBD-rAAV prime/RBD-rAAV boost vaccinated animals. Increased production of IL-2-secreting cells. Induction of SARS-CoV-specific IgG production. (Du et al., 2008) BALB/c (Du et al., 2008) Mice were Mice were separated into 4 groups (9 mice per group) and primed with RBD-rAAV [intramuscular (i.m.), 2 × 10^11 VP /200 μl)] or RBD-peptides (N50 and N60, 50 μg each) plus CpG ODN (25 μg) [subcutaneous, (s.c.)] or blank AAV, and boosted with RBD-rAAV or RBD-Pep or AAV, respectively (Du et al., 2008). SARS-CoV viral load in lung tissues was significantly reduced in mice vaccinated with RBD-Pep. Very low level of viral load was detected in lung tissues of RBD-rAAV prime/RBD-Pep boost group, similar to that in lung tissues of RBD-rAAV prime/RBD-rAAV boost group. Vaccination of RBD-rAAV prime/RBD-peptide boost was able to significantly inhibit SARS-CoV infection (Du et al., 2008). Mice intranasally challenged with SARS-CoV strain GZ50 40 days post-vaccination (Du et al., 2008). SARS-CoV Ad S/N vaccine Recombinant vector vaccine Research attenuated adenovirus[Ref5106:See et al., 2006] intranasal immunization A combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (See et al., 2006) intranasal immunization S protein, N (See et al., 2006) Recombinant vector construction Recombinant vector construction Quantifiable humoral response with presence of SARS-CoV-specific IgG1 and a significant reduction in level of SARS-CoV RNA in lung titers. Production of IFN-γ. (See et al., 2006) 129S6/SvEv (See et al., 2006) Mouse was immunized on day 0 and week 4 (See et al., 2006) Partially protected (See et al., 2006) Mouse was immunized on day 0 and week 4 and then challenged with SARS-COV Tor2 at week 7 (See et al., 2006). SARS-CoV CRT-N vaccine DNA vaccine Research Intravenous injection (i.v.) A DNA vaccine encoding CRT linked to a SARS-CoV N (Kim et al., 2004) calreticulin (Kim et al., 2004) Intravenous injection (i.v.) N protein (Kim et al., 2004) Significantly increased neutralizing antibody titre to N protein DNA vaccine (Vaccine 5732) and significantly greater count of INF-gamma CD8_ lymphocytes within splenocytes (Kim et al., 2004) C57BL/6 (Kim et al., 2004) DNA-coated gold particles were prepared and delivered to the shaved abdominal regions of mice using a helium-driven gene gun (Bio-Rad) with a discharge pressure of 400 lb/in2. C57BL/6 mice were immunized with 2 μg of the plasmid encoding CRT/N protein. The mice received two boosters with the same dose at a 1-week interval. (Kim et al., 2004) significantly reduced viral titer load(Kim et al., 2004) Vaccinated mice challenged with DNA encoding CRT/Na nd challenged these mice with Vac-N or Vac-WT (Recombinant vaccinnia virus expressing SARS N protein or wild-type vaccinia virus, respectively) intranasally or intravenously 1 week after the last vaccination (Kim et al., 2004) SARS-CoV CTLA4-S DNA vaccine DNA vaccine Research Intramuscular injection (i.m.) CTLA4HingeSARS800 DNA from SARS-CoV S protein vaccine (Woo et al., 2005) Intramuscular injection (i.m.) S protein(Woo et al., 2005) DNA vaccine construction Induced neutralizing antibody, high IgG levels, lymphocyte proliferation, production of IFN-γ, production of IL-4 (48hrs) (Woo et al., 2005) Balb/c (H-2d) (Woo et al., 2005) 100 μg intramuscular administration of vaccine, then 50 μg intraperitoneal injection at 14 and 28 days (Woo et al., 2005) SARS-CoV E gene mutant vaccine VO_0002993 Live, attenuated vaccine Research intranasal immunization intranasal immunization Gene mutation This E gene is from SARS coronavirus (Lamirande et al., 2008). Induced neutralizing antibodies. (Lamirande et al., 2008) LVG (SYR) (Lamirande et al., 2008) An E gene mutant is attenuated in hamsters (Lamirande et al., 2008). An E gene mutant induces significant protection in hamsters from challenge with wild type SARS (Lamirande et al., 2008). SARS-CoV M protein DNA vaccine DNA vaccine Research Intramuscular injection (i.m.) DNA vaccine made from recombinant plasmid containing membrane protein (M) sequence constructed then expressed and purified from E. coli bacteria (Shi et al., 2006) Intramuscular injection (i.m.) membrane protein (M) (Shi et al., 2006) DNA vaccine construction N-specific IgG (mostly IgG2a) (Shi et al., 2006) Balb/c (Shi et al., 2006) 20 μg of vaccine intramuscular injection (Shi et al., 2006) N-specific IgG (mostly IgG2a) (Shi et al., 2006) Microtus brandti raddes (Shi et al., 2006) 100 μg injected three times at an interval of 7 days (Shi et al., 2006) SARS-CoV N + SARS-CoV M DNA vaccine DNA vaccine Research Intramuscular injection (i.m.) DNA vaccine made from recombinant plasmids containing membrane protein (M) and nucleocapsid protein (N) sequences constructed then expressed and purified from E. coli bacteria (Shi et al., 2006) Intramuscular injection (i.m.) N, membrane protein (M) (Shi et al., 2006) DNA vaccine construction DNA vaccine construction increased N-specific antibodies compared to Vaccine 5732, increased lymphocyte proliferation specific to N antigen than Vaccine 5732 (Shi et al., 2006) 100 μg injected (Shi et al., 2006) 6/7 voles protected (Shi et al., 2006) 100 μg injected (Shi et al., 2006) Production of N-specific IgG antibodies (paricularly IgG2a), Lymphocyte proliferation, Production of IFN-γ, IL-2, IL-4, Increased CD4+ and CD8+ levels (Shi et al., 2006) Balb/c (Shi et al., 2006) 20 μg of intramuscular vaccine injection (Shi et al., 2006) SARS-CoV N protein DNA vaccine Subunit vaccine Research Intramuscular injection (i.m.) DNA vaccine made from recombinant plasmid containing nucleocapsid protein (N) sequence constructed then expressed and purified from E. coli bacteria (Shi et al., 2006) Intramuscular injection (i.m.) N (Shi et al., 2006) Recombinant protein preparation Significantly increased neutralizing antibody titer to N protein DNA vaccine and significantl count of INF-gamma CD8_ lymphocytes within splenocytes (Kim et al., 2004) DNA-coated gold particles were prepared and delivered to the shaved abdominal regions of mice using a helium-driven gene gun (Bio-Rad) with a discharge pressure of 400 lb/in2. C57BL/6 mice were immunized with 2 μg of the plasmid encoding N protein. The mice received two boosters with the same dose at a 1-week interval. (Kim et al., 2004) reduced viral titer load(Kim et al., 2004) Challenge Protocol: Vaccinated mice challenged with DNA encoding N and challenged these mice with Vac-N or Vac-WT (Recombinant vaccinnia virus expressing SARS N protein or wild-type vaccinia virus, respectively) intranasally or intravenously 1 week after the last vaccination (Kim et al., 2004) Production of N-specific IgG antibodies (paricularly IgG2a), Lymphocyte proliferation, Production of IFN-γ, IL-2, IL-4, Increased CD4+ and CD8+ levels (Shi et al., 2006) Balb/c (Shi et al., 2006) 20 μg of vaccine intramuscular injection (Shi et al., 2006) increased N-specific antibodies, increased lymphocye proliferation specific to N antigen (Shi et al., 2006) Microtus brandti raddes (Shi et al., 2006) 100 μg injected (Shi et al., 2006) 100 μg injected three times at an interval of 7 days and then challenged with live SARS-CoV (PUMC01) (Shi et al., 2006) SARS-CoV pCI-N DNA from vaccine DNA vaccine Research Intramuscular injection (i.m.) A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed and expressed in Escherichia coli DH5alpha (Zhao et al., 2005) Intramuscular injection (i.m.) S protein (Zhao et al., 2005) DNA vaccine construction Anti-N immunoglobulins (specifically IgG2a) and splenocytes proliferative responses against N protein, splenocyte production of IFN-γ, IL-2, IL-4, IL-10, production of N-specific CD8+ T cells, delayed-type hypersensitivity response (Zhao et al., 2005) Balb/c(Zhao et al., 2005) 200 μg of Vaccine 573 in both tibialis anterior muscles three times at 2-week intervals (Zhao et al., 2005) Delayed hypersensitivity response (Zhao et al., 2005) SARS-CoV rVV-SARS-N Recombinant vector vaccine Research recombinant vaccinia virus [Ref5384:Zhou et al., 2006] intranasal immunization recombinant vaccinia virus expressing the N protein (rVV-SARS-N) intranasal immunization N protein (Zhao et al., 2016) Production of N-specific CD4+ T cells, Production of IFN-γ, Production of IL-10, Increased mobilization of CD8+ cells to infected lung. (Zhao et al., 2016) BALB/c Mice were vaccinated with rVV-SARS-N i.n. and boosted 6–7 weeks later. protected (Zhao et al., 2016) SARS-CoV S Baculovirus Vaccine VO_0005151 Recombinant vector vaccine Research Baculovirus [Ref5384:Zhou et al., 2006] intranasal immunization recombinant SARS-CoV spike (S) glycoprotein viral vaccine produced in insect cells that is expressed by baculovirus (Zhou et al., 2006) intranasal immunization S protein of SARS-CoV (Zhou et al., 2006) SARS-CoV Salmonella-CTLA4-S DNA vaccine DNA vaccine Research Oral oral live-attenuated auxotrophic S. typhimurium aroA strain SL7207 that contained CTLA4HingeSARS800 DNA vaccine (Woo et al., 2005) Oral S protein (Woo et al., 2005) Recombinant vector construction Immune Response Description: neutralizing antibody titers of <1:20–1:160, lymphocyte proliteration, production of IFN-γ, production of IL-4 (48hrs) (Woo et al., 2005) Balb/ (H-2d) (Woo et al., 2005) : oral injection of 6e9 live attenuated Salmonella typhimurium that underwent transfection of CTLA4-, then 50 μg spike polypeptide administered via intraperitoneal injection on days 28 and 42. (Woo et al., 2005) SARS-CoV Salmonella-tPA-S DNA vaccine DNA vaccine Research Oral oral live-attenuated auxotrophic S. typhimurium aroA strain SL7207 that contained tPA-optimize800 DNA vaccine (Woo et al., 2005) Oral S protein (Woo et al., 2005) Recombinant vector construction neutralizing antibody titers of <1:20–1:160, lymphocyte proliteration, production of IFN-γ, production of IL-4 (48hrs) (Woo et al., 2005) Balb/c (H-2d) (Woo et al., 2005) oral injection of 6e9 live attenuated Salmonella typhimurium that underwent transfection of tPA-S (Woo et al., 2005) SARS-CoV tPA-S DNA vaccine DNA vaccine Research Intramuscular injection (i.m.) tPA-optimize800 DNA vaccine of SARS-CoV S protein (Woo et al., 2005) Intramuscular injection (i.m.) S protein (Woo et al., 2005) DNA vaccine construction neutralizing antibody titers of <1:20–1:160, lymphocyte proliteration, production of IFN-γ, production of IL-4 (48hrs) (Woo et al., 2005) Balb/c (H-2d) (Woo et al., 2005) 100 μg of intramuscular administration of vaccine then 50 μg intraperitoneal injection of spike polypeptide at 28 and 42 days (Woo et al., 2005) SARS-CoV VLP-MHV + alum vaccine Virus like particle vaccine Licensed Nucleocapsid (N), envelope (E) and membrane (M) proteins from mouse hepatitis coronavirus (MHV) (Tseng et al., 2012) Intramuscular injection (i.m.) Virus like particle vaccine produced from SARS-CoV spike protein (S) and the Nucleocapsid (N), envelope (E) and membrane (M) proteins from mouse hepatitis coronavirus (MHV) (Tseng et al., 2012) alum(Tseng et al., 2012) Intramuscular injection (i.m.) SARS-CoV spike protein (S) (Tseng et al., 2012) Increased titer of neutralizing antibodies and reduced viral titer (Tseng et al., 2012) BALB/c Each mouse received 100 µl injection containing 2 µg of vaccine intramuscularly on days 0 and 28 (Tseng et al., 2012) protected (Tseng et al., 2012) eosinophil infiltration in the lung lesions after challenge (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 10^6TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) SARS-CoV VLP-MHV vaccine Virus like particle vaccine Research Nucleocapsid (N), envelope (E) and membrane (M) proteins from mouse hepatitis coronavirus (MHV) [Ref5382:Tseng et al., 2012] Intramuscular injection (i.m.) Virus like particle vaccine produced from SARS-CoV spike protein (S) and the Nucleocapsid (N), envelope (E) and membrane (M) proteins from mouse hepatitis coronavirus (MHV) (Tseng et al., 2012) Intramuscular injection (i.m.) SARS-CoV spike protein (S) (Tseng et al., 2012) Induced neutralizing antibody, Neutrophil + eosinophil infiltration, Th2-type hypersensitivity reaction. (Tseng et al., 2012) BALB/c Each mouse received 100 µl injection containing 2 µg of vaccine intramuscularly on days 0 and 28 (Tseng et al., 2012) protected (Tseng et al., 2012) eosinophil infiltration in the lung lesions after challenge (Tseng et al., 2012) On day 56 after first vaccination, each mice was challenged challenged with 106TCID50/60 µl of SARS-CoV intranasally (IN) and euthanized on day 58 (Tseng et al., 2012) UV Inactivated SARS-CoV vaccine Live, attenuated vaccine Licensed Intramuscular injection (i.m.) Ultraviolet radiation applied to SARS virus. Vaccine causes eosinophilic immunopathology to SARS while providing protection (Iwata-Yoshikawa et al., 2014) Intramuscular injection (i.m.) whole virus(Iwata-Yoshikawa et al., 2014) Induced neutralizing antibodies, Lymphocyte infiltration, Upregulation of IL-4 and CCL24, CD11b+ cells upregulated genes associated with eosinophil induction (Iwata-Yoshikawa et al., 2014). BALB/c 10 μg UV-V subcutaneously injected in back and reimmunized 6 to 7 weeks later (Iwata-Yoshikawa et al., 2014) Most mice survived challenge after weight loss and respiratory disease (Iwata-Yoshikawa et al., 2014) Eosinophil infiltration present in the lungs (Iwata-Yoshikawa et al., 2014) 10 week old BALB/c mice were vaccinated with 10 μg UV-V and boosted 6 weeks later. Four weeks afterwards, the animals were inoculated in the left nostril with 106.5 TCID50 in 30 μl of F-musX(Iwata-Yoshikawa et al., 2014). UV-Inactivated SARS-CoV + TLR Agonist Vaccine Inactivated or "killed" vaccine Licensed subcutaneous injection Ultraviolet radiation is used to inactivate SARS-CoV and a Toll-Like Receptor Agonist Adjuvant is added to prevent eosinophilic immunopathology (Iwata-Yoshikawa et al., 2014). 1 μg lipopolysaccharide (LPS) (Sigma-Aldrich, St. Louis, MO), 2.5 μg poly(I·C) (Invitrogen, San Diego, CA), and 0.1 μg poly(U) (Invitrogen) per immunization (Iwata-Yoshikawa et al., 2014) subcutaneous injection whole virus (Iwata-Yoshikawa et al., 2014) Induced neutralizing antibodies (More than in UV-V), Lymphocyte infiltration, High levels of CXCL10 and CXCL1, Production of IFN-β, Upregulation of TNF-α1 (Iwata-Yoshikawa et al., 2014) BALB/c 10 μg of UV-Inactivated SARS-CoV + TLR Agonist Vaccine subcutaneously injected in back and reimmunized 6 to 7 weeks later (Iwata-Yoshikawa et al., 2014) All mice survived challenge (Iwata-Yoshikawa et al., 2014). Minor eosinophil lung infiltration (Iwata-Yoshikawa et al., 2014) 10 week old BALB/c mice were vaccinated with 10 μg UV-V and boosted 6 weeks later. Four weeks afterwards, the animals were inoculated in the left nostril with 106.5 TCID50 in 30 μl of F-musX(Iwata-Yoshikawa et al., 2014) VRC-SRSDNA015-00-VP vaccine VO_0005146 DNA vaccine Clinical trial Intramuscular injection (i.m.) A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein. (Martin et al., 2008) Intramuscular injection (i.m.) S protein (Martin et al., 2008) S-specific antibody, neutralizing antibodies present. S-specific CD4+ T cell response was detected in all patients, where on 20% had S-specific CD8+ T cell responses. (Martin et al., 2008) Injections on study days 0, 28, and 56 at a 4 mg dose in the lateral deltoid muscle (Martin et al., 2008) Chills, fever, headache, injection site pain, malaise, myalgia, redness, swelling, tenderness (Martin et al., 2008) VRP-MERS-N vaccine VO_0005130 Viral Like Particle Vaccine Research Venezuelan equine encephalitis replicons (Zhao et al., 2016) intranasal immunization Venezuelan equine encephalitis replicons bearing epitopes of N protein from MERS(Zhao et al., 2016). Identical to VRP-MERS-N vaccine (Vaccine 5748). intranasal immunization N protein (Zhao et al., 2016) Reduced viral titre, production of N-specific CD4+ T cells, Production of IFN-γ, Production of CD8+ T cells. (Zhao et al., 2016) Balb/c (H-2d) Mice were challenged 4-6 weeks after boosting (Zhao et al., 2016) VRP-SARS-N vaccine VO_0005131 Viral Like Particle Vaccine Licensed Venezuelan equine encephalitis replicons (VRP) [Ref5388:Zhao et al., 2016] intranasal immunization Venezuelan equine encephalitis replicons (VRP) encoding a SARS-CoV CD4+ T cell epitope vaccinated intranasally. Does not have same efficacy if vaccinated subcutaneously (Zhao et al., 2016) Identical to VRP-SARS-N vaccine (Vaccine 5755). intranasal immunization CD4+ T cell epitope in the nucleocapsid (N) protein of SARS-CoV (N353) (Zhao et al., 2016) Decreased viral titre, increase in N-specific CD4+ T cells and IFN-γ in lungs, production of IL-10, increased mobilization of CD8+ cells to infected lung. (Zhao et al., 2016) BALB/c vaccinated BALB/c mice twice at 6–7 week intervals with VRP-SARS-N at 100 PFU (Zhao et al., 2016) nearly complete protection at 100 pfu, protected at 500 and 1000 pfu doses (Zhao et al., 2016) challenged 6-7 weeks after second vaccination with doses from 100, 500, 1,000 PFU of SARS-CoV (Zhao et al., 2005) Better results compared to different vaccination routes (Zhao et al., 2016). envelope protein (E) gene of SARS-CoV Severe acute respiratory syndrome-related coronavirus 1489671 29836499 sars4 NP_828854 694009 26116 26346 + protein E 6.3 6972.52 76 E. coli expression reported by Shen et al. (2003) >gi|30271926:26116-26346 SARS coronavirus, complete genome TATGTACTCATTCGTTTCGGAAGAAACAGGTACGTTAATAGTTAATAGCGTACTTCTTTTTCTTGCTTTC GTGGTATTCTTGCTAGTCACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATATTG TTAACGTGAGTTTAGTAAAACCAACGGTTTACGTCTACTCGCGTGTTAAAAATCTGAACTCTTCTGAAGG AGTTCCTGATCTTCTGGTCTA >gi|29836499|ref|NP_828854.1| protein E [Severe acute respiratory syndrome-related coronavirus] MYSFVSEETGTLIVNSVLLFLAFVVFLLVTLAILTALRLCAYCCNIVNVSLVKPTVYVYSRVKNLNSSEG VPDLLV Virmugen An E mutant is attenuated in hamsters and induces significant protection from challenge with wild type SARS [Ref1677:Lamirande et al., 2008]. membrane protein (M) gene of SARS-CoV SARS-CoV ABD75314 CDD:279907 347537 ? membrane protein 10.04 24329.5 279 Coronavirus M matrix/glycoprotein; pfam01635 >ABD75314.1 membrane protein [Bat SARS CoV Rf1/2004] MAENGTISVEELKRLLEQWNLVIGFLFLAWIMLLQFAYSNRNRLLYIIKLVFLWLLWPVTLACFVLAAVY RINWVTGGIAIAMACIVGLMWLSYFVASFRLFARTRSMWSFNPETNILLNVPLRGTIVTRPLMESELVIG AVIIRGHLRMAGHSLGRCDIKDLPKEITVATSRTLSYYKLGASQRVGTDSGFAAYNRYRIGNYKLNTDHS GSNDNIALLVQ Protective antigen [Ref4975:Demurtas et al., 2016] nucleocapsid protein (N) gene of SARS-CoV SARS-CoV AAZ67049 CDD:279305 349344 nucleocapsid protein 10.79 45847.78 486 Coronavirus nucleocapsid protein; pfam00937 >AAZ67049.1 nucleocapsid protein [Bat SARS CoV Rp3/2004] MSDNGPQNQRSAPRITFGGPTDSTDNNQDGGRSGARPKQRRPQGLPNNTASWFTALTQHGKEELRFPRGQ GVPINTNSGKDDQIGYYRRATRRVRGGDGKMKELSPRWYFYYLGTGPEASLPYGANKEGIVWVATEGALN TPKDHIGTRNPNNNAAIVLQLPQGTTLPKGFYAEGSRGGSQASSRSSSRSRGNSRNSTPGSSRGNSPARM ASGGGETALALLLLDRLNQLESKVSGRSQQQQGQTVTKKSAAEASKKPRQKRTATKQYNVTQAFGRRGPE QTQGNFGDQELIRQGTDYKHWPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYHGAIKLDDKDPQFKDNV ILLNKHIDAYKIFPPTEPKKDKKKKTDEAQPLPQRQKKQPTVTLLPAADMDDFSRQLQNSMSGASADSTQ A Protective antigen [Ref4975:Demurtas et al., 2016] S protein gene of SARS-CoV SARS coronavirus VO_0011320 1489668 29836496 sars2 NP_828851 227859 21491 25258 + E2 glycoprotein precursor 5.6 130077.89 1255 As established by Krokhin et al. (2003), the glycosylated spike protein (as well as the nucleocapsid protein) can be detected in infected cell culture supernatants with antisera from SARS patients. >NC_004718.3:21491-25258 SARS coronavirus, complete genome CATGTTTATTTTCTTATTATTTCTTACTCTCACTAGTGGTAGTGACCTTGACCGGTGCACCACTTTTGAT GATGTTCAAGCTCCTAATTACACTCAACATACTTCATCTATGAGGGGGGTTTACTATCCTGATGAAATTT TTAGATCAGACACTCTTTATTTAACTCAGGATTTATTTCTTCCATTTTATTCTAATGTTACAGGGTTTCA TACTATTAATCATACGTTTGGCAACCCTGTCATACCTTTTAAGGATGGTATTTATTTTGCTGCCACAGAG AAATCAAATGTTGTCCGTGGTTGGGTTTTTGGTTCTACCATGAACAACAAGTCACAGTCGGTGATTATTA TTAACAATTCTACTAATGTTGTTATACGAGCATGTAACTTTGAATTGTGTGACAACCCTTTCTTTGCTGT TTCTAAACCCATGGGTACACAGACACATACTATGATATTCGATAATGCATTTAATTGCACTTTCGAGTAC ATATCTGATGCCTTTTCGCTTGATGTTTCAGAAAAGTCAGGTAATTTTAAACACTTACGAGAGTTTGTGT TTAAAAATAAAGATGGGTTTCTCTATGTTTATAAGGGCTATCAACCTATAGATGTAGTTCGTGATCTACC TTCTGGTTTTAACACTTTGAAACCTATTTTTAAGTTGCCTCTTGGTATTAACATTACAAATTTTAGAGCC ATTCTTACAGCCTTTTCACCTGCTCAAGACATTTGGGGCACGTCAGCTGCAGCCTATTTTGTTGGCTATT TAAAGCCAACTACATTTATGCTCAAGTATGATGAAAATGGTACAATCACAGATGCTGTTGATTGTTCTCA AAATCCACTTGCTGAACTCAAATGCTCTGTTAAGAGCTTTGAGATTGACAAAGGAATTTACCAGACCTCT AATTTCAGGGTTGTTCCCTCAGGAGATGTTGTGAGATTCCCTAATATTACAAACTTGTGTCCTTTTGGAG AGGTTTTTAATGCTACTAAATTCCCTTCTGTCTATGCATGGGAGAGAAAAAAAATTTCTAATTGTGTTGC TGATTACTCTGTGCTCTACAACTCAACATTTTTTTCAACCTTTAAGTGCTATGGCGTTTCTGCCACTAAG TTGAATGATCTTTGCTTCTCCAATGTCTATGCAGATTCTTTTGTAGTCAAGGGAGATGATGTAAGACAAA TAGCGCCAGGACAAACTGGTGTTATTGCTGATTATAATTATAAATTGCCAGATGATTTCATGGGTTGTGT CCTTGCTTGGAATACTAGGAACATTGATGCTACTTCAACTGGTAATTATAATTATAAATATAGGTATCTT AGACATGGCAAGCTTAGGCCCTTTGAGAGAGACATATCTAATGTGCCTTTCTCCCCTGATGGCAAACCTT GCACCCCACCTGCTCTTAATTGTTATTGGCCATTAAATGATTATGGTTTTTACACCACTACTGGCATTGG CTACCAACCTTACAGAGTTGTAGTACTTTCTTTTGAACTTTTAAATGCACCGGCCACGGTTTGTGGACCA AAATTATCCACTGACCTTATTAAGAACCAGTGTGTCAATTTTAATTTTAATGGACTCACTGGTACTGGTG TGTTAACTCCTTCTTCAAAGAGATTTCAACCATTTCAACAATTTGGCCGTGATGTTTCTGATTTCACTGA TTCCGTTCGAGATCCTAAAACATCTGAAATATTAGACATTTCACCTTGCGCTTTTGGGGGTGTAAGTGTA ATTACACCTGGAACAAATGCTTCATCTGAAGTTGCTGTTCTATATCAAGATGTTAACTGCACTGATGTTT CTACAGCAATTCATGCAGATCAACTCACACCAGCTTGGCGCATATATTCTACTGGAAACAATGTATTCCA GACTCAAGCAGGCTGTCTTATAGGAGCTGAGCATGTCGACACTTCTTATGAGTGCGACATTCCTATTGGA GCTGGCATTTGTGCTAGTTACCATACAGTTTCTTTATTACGTAGTACTAGCCAAAAATCTATTGTGGCTT ATACTATGTCTTTAGGTGCTGATAGTTCAATTGCTTACTCTAATAACACCATTGCTATACCTACTAACTT TTCAATTAGCATTACTACAGAAGTAATGCCTGTTTCTATGGCTAAAACCTCCGTAGATTGTAATATGTAC ATCTGCGGAGATTCTACTGAATGTGCTAATTTGCTTCTCCAATATGGTAGCTTTTGCACACAACTAAATC GTGCACTCTCAGGTATTGCTGCTGAACAGGATCGCAACACACGTGAAGTGTTCGCTCAAGTCAAACAAAT GTACAAAACCCCAACTTTGAAATATTTTGGTGGTTTTAATTTTTCACAAATATTACCTGACCCTCTAAAG CCAACTAAGAGGTCTTTTATTGAGGACTTGCTCTTTAATAAGGTGACACTCGCTGATGCTGGCTTCATGA AGCAATATGGCGAATGCCTAGGTGATATTAATGCTAGAGATCTCATTTGTGCGCAGAAGTTCAATGGACT TACAGTGTTGCCACCTCTGCTCACTGATGATATGATTGCTGCCTACACTGCTGCTCTAGTTAGTGGTACT GCCACTGCTGGATGGACATTTGGTGCTGGCGCTGCTCTTCAAATACCTTTTGCTATGCAAATGGCATATA GGTTCAATGGCATTGGAGTTACCCAAAATGTTCTCTATGAGAACCAAAAACAAATCGCCAACCAATTTAA CAAGGCGATTAGTCAAATTCAAGAATCACTTACAACAACATCAACTGCATTGGGCAAGCTGCAAGACGTT GTTAACCAGAATGCTCAAGCATTAAACACACTTGTTAAACAACTTAGCTCTAATTTTGGTGCAATTTCAA GTGTGCTAAATGATATCCTTTCGCGACTTGATAAAGTCGAGGCGGAGGTACAAATTGACAGGTTAATTAC AGGCAGACTTCAAAGCCTTCAAACCTATGTAACACAACAACTAATCAGGGCTGCTGAAATCAGGGCTTCT GCTAATCTTGCTGCTACTAAAATGTCTGAGTGTGTTCTTGGACAATCAAAAAGAGTTGACTTTTGTGGAA AGGGCTACCACCTTATGTCCTTCCCACAAGCAGCCCCGCATGGTGTTGTCTTCCTACATGTCACGTATGT GCCATCCCAGGAGAGGAACTTCACCACAGCGCCAGCAATTTGTCATGAAGGCAAAGCATACTTCCCTCGT GAAGGTGTTTTTGTGTTTAATGGCACTTCTTGGTTTATTACACAGAGGAACTTCTTTTCTCCACAAATAA TTACTACAGACAATACATTTGTCTCAGGAAATTGTGATGTCGTTATTGGCATCATTAACAACACAGTTTA TGATCCTCTGCAACCTGAGCTTGACTCATTCAAAGAAGAGCTGGACAAGTACTTCAAAAATCATACATCA CCAGATGTTGATCTTGGCGACATTTCAGGCATTAACGCTTCTGTCGTCAACATTCAAAAAGAAATTGACC GCCTCAATGAGGTCGCTAAAAATTTAAATGAATCACTCATTGACCTTCAAGAATTGGGAAAATATGAGCA ATATATTAAATGGCCTTGGTATGTTTGGCTCGGCTTCATTGCTGGACTAATTGCCATCGTCATGGTTACA ATCTTGCTTTGTTGCATGACTAGTTGTTGCAGTTGCCTCAAGGGTGCATGCTCTTGTGGTTCTTGCTGCA AGTTTGATGAGGATGACTCTGAGCCAGTTCTCAAGGGTGTCAAATTACATTACACATA >NP_828851.1 E2 glycoprotein precursor [SARS coronavirus] MFIFLLFLTLTSGSDLDRCTTFDDVQAPNYTQHTSSMRGVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFH TINHTFGNPVIPFKDGIYFAATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFFAV SKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVFKNKDGFLYVYKGYQPIDVVRDLP SGFNTLKPIFKLPLGINITNFRAILTAFSPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQ NPLAELKCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPSVYAWERKKISNCVA DYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCV LAWNTRNIDATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIG YQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNFNGLTGTGVLTPSSKRFQPFQQFGRDVSDFTD SVRDPKTSEILDISPCAFGGVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNNVFQ TQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNF SISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQM YKTPTLKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGL TVLPPLLTDDMIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFN KAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLIT GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYV PSQERNFTTAPAICHEGKAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNTVY DPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQ YIKWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT Protective antigen The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. A previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. The immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost were assessed. Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone [Ref1380:Du et al., 2008]. 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