A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model
<p><b>Vaccination schedule</b>. Syrian hamsters were immunized on day 0 with 10 μg of chemically inactivated CORAVAX or FILORAB1 with Seppic (SEPIVAC SWE) adjuvant. The animals were challenged on day 39 with a dose of 10<sup>4</sup> PFU of the SARS-CoV-2 isolate USA_WA1/2020. Serum was collected from each hamster on days 0, 14, and 28 and at necropsy (days 42, 46, or 53) for analysis. Animals were necropsied on days 42 (day 3 p.c.), 46 (day 7 p.c.), and 53 (day 14 p.c.). Created with BioRender.com.</p> "> Figure 2
<p><b>SARS-CoV-2 immune responses.</b> Serum samples collected from each hamster were evaluated for SARS-CoV-2 S-specific immune responses by (<b>A</b>) ELISA, anti-SARS-CoV-2 S1 IgG responses represented as EC50 titers over time, (<b>B</b>) ELISA, anti-SARS-CoV-2 RBD responses, and (<b>C</b>), ELISA, anti-SARS-CoV-2 S1 IgG2/3 responses. The CORAVAX vaccine group is shown in blue circles, and the FILORAB1 group is in black triangles. For (<b>A</b>–<b>C</b>), mean titers ± SD are depicted for each group per time point, and <span class="html-italic">p</span> values were determined by Mann–Whitney test. Only significant differences are depicted. <span class="html-italic">p values are defined as: p</span> > 0.123 (ns), <span class="html-italic">p</span> < 0.033 (*), <span class="html-italic">p</span> < 0.002 (**), <span class="html-italic">p</span> < 0.001 (***). Red arrow indicates the day of challenge (day 39).</p> "> Figure 3
<p><b>SARS-CoV-2 virus-neutralizing antibody responses.</b> Serum samples collected from each hamster were evaluated for SARS-CoV-2 S-specific virus-neutralizing antibody (VNA) responses using 100 PFU of SARS-CoV-2 isolate USA_WA1/2020.100%. VNA titers are depicted for hamster sera at different time points along with convalescent sera (<span class="html-italic">n</span> = 7) and negative control sera (<span class="html-italic">n</span> = 7). The groups are depicted with the following symbols: CORAVAX group in blue circles, FILORAB1 control group in black triangles, convalescent sera in red squares, and negative control sera in grey diamonds. Mean titers ± SD are depicted for each group per time point, and <span class="html-italic">p</span> values were determined by Mann–Whitney test. Only significant differences are depicted. <span class="html-italic">p values are defined as: p</span> > 0.123 (ns), <span class="html-italic">p</span> < 0.033 (*), <span class="html-italic">p</span> < 0.002 (**), <span class="html-italic">p</span> < 0.001 (***). LLOD stands for lower limit of detection.</p> "> Figure 4
<p><b>Hamster body weight after SARS-CoV-2 infection</b>. Hamsters were vaccinated on day 0 and challenged intranasally with 10<sup>4</sup> PFU SARS-CoV-2 on day 39. Percent change in body weight. CORAVAX vaccine group is shown in blue, and FILORAB1 group is in black. <span class="html-italic">n</span> = 15 for FILORAB1 group (5 hamsters each euthanized on days 3, 7, and 14 p.c.) and <span class="html-italic">n</span> = 15 for CORAVAX group (5 hamsters each euthanized on days 3, 7, and 14 p.c.). Body weight <span class="html-italic">p</span> value determined by Wilcoxon test; <span class="html-italic">p</span> > 0.123 (ns), <span class="html-italic">p</span> < 0.033 (*), <span class="html-italic">p</span> < 0.002 (**), <span class="html-italic">p</span> < 0.001 (***).</p> "> Figure 5
<p><b>SARS-CoV-2 tissue viral load in hamsters.</b> Hamsters were challenged intranasally with 10<sup>4</sup> PFU SARS-CoV-2, and five of the animals in each group were euthanized on days 3, 7, and 14 p.c. Right lungs (<b>A</b>,<b>C</b>) and nasal turbinates (<b>B</b>,<b>D</b>) from each animal were homogenized in media, and viral loads were determined by qRT-PCR (A, B) or by TCID<sub>50</sub> assays on Vero E6 cells (<b>C</b>,<b>D</b>). The limit of detection for the qRT-PCR assay is 10 copies. The limit of detection for the plaque assay is 50 PFU/mL per lung/nasal turbinate tissue. The CORAVAX vaccine group is shown in blue, and the FILORAB1 group is in black. Data represent mean ± S.D., <span class="html-italic">n</span> = 5 for FILORAB1 group days 3, 7, and 14 time points, and <span class="html-italic">n</span> = 5 for CORAVAX group days 3, 7, and 15 time points; <span class="html-italic">p</span> values were determined by Mann–Whitney test; <span class="html-italic">p</span> > 0.123 (ns), <span class="html-italic">p</span> < 0.033 (*), <span class="html-italic">p</span> < 0.002 (**), <span class="html-italic">p</span> < 0.001 (***). Only significant differences are depicted.</p> "> Figure 6
<p><b>SARS-CoV-2 lung pathology.</b> Representative histological images of SARS-CoV-2 infection in control and vaccinated hamster lungs. (<b>A</b>,<b>C</b>,<b>E</b>): CORAVAX vaccinated on days 3, 7, and 14 p.c. (<b>B</b>,<b>D</b>,<b>F</b>): FILORAB1 control on days 3, 7, and 14 p.c. All images were taken with 10× objective and 0.5 camera adaptor; the scale bar in every image equals 100 μm. The images show significantly less lung inflammation in the vaccinated animals than in the control unvaccinated animals. The difference is more prominent on day 3 p.c., followed by day 7 p.c.</p> "> Figure 7
<p><b>Comparative pathology scores for lungs from CORAVAX-vaccinated and control hamsters post-SARS-CoV-2 challenge.</b> Overall lung pathology scores on days 3, 7, and 14 days p.c. The pathology scores (mean) were calculated based on the criteria described in <a href="#app1-viruses-14-01126" class="html-app">Table S1</a>. The CORAVAX vaccine group is shown in blue circles, and the FILORAB1 control group is in black triangles. Data represent mean ± S.D., <span class="html-italic">n</span> = 5 for FILORAB1 group and CORAVAX group for days 3, 7, and 15 time points; <span class="html-italic">p</span> > 0.123 (ns), <span class="html-italic">p</span> < 0.033 (*), <span class="html-italic">p</span> < 0.002 (**), <span class="html-italic">p</span> < 0.001 (***). Only significant differences are depicted.</p> "> Figure 8
<p><b>SARS-CoV-2 nucleoprotein antigen lung staining.</b> Representative histological images of SARS-CoV-2 nucleoprotein (N) antigen staining in the lungs of control and vaccinated hamsters. (<b>A</b>,<b>C</b>,<b>E</b>) CORAVAX days 3, 7, and 14 p.c. (B,D,F) FILORAB1 days 3, 7, and 14 p.c. The presence of the SARS-CoV-2 N antigen is indicated by the brown DAB (3, 3′-diaminobenzidine) stain in the lungs. A significantly higher amount of N antigen staining is observed in the FILORAB1 lungs (<b>B</b>) than in CORAVAX lungs (<b>A</b>) on day 3 p.c. On day 7 p.c., immunohistochemical stain for the SARS-CoV-2 nucleoprotein antigen shows scattered positive cells in the control group (<b>D</b>) and no definite positive cells in the vaccinated group (<b>C</b>). SARS-CoV-2 N antigen staining is absent in the FILORAB1 (<b>F</b>) and CORAVAX lungs (<b>E</b>) on day 14 p.c. All images were taken with 10× objective and 0.5 camera adaptor; the scale bar in every image equals 100 μm.</p> "> Figure 9
<p><b>A single dose of CORAVAX immunization prevents a cytokine storm in the lungs</b>. The CORAVAX vaccine group is shown in blue circles, and the FILORAB1 control group is in black triangles. Total RNA was extracted from the lungs of hamsters necropsied on days 3, 7, and 14 after challenge with SARS-CoV-2. Hamster (<b>A</b>) IFN-γ, (<b>B</b>) IFN-α, (<b>C</b>) IL-10, (<b>D</b>) IL-6, (<b>E</b>) CCL5, (<b>F</b>) IL-4, (<b>G</b>) CCL3, (<b>H</b>) IL-2, (<b>I</b>) IL-21, (<b>J</b>) TGF-β1, (<b>K</b>) TNF-α, and (<b>L</b>) IL-17. Cytokine/chemokine mRNAs were quantified by real-time RT-PCR. γ-Actin mRNA was used as an internal control. Data are shown as fold change in gene expression compared to normal animals (unimmunized and unchallenged) after normalization. Data were analyzed using Mann–Whitney test for each time point (* <span class="html-italic">p</span> < 0.05; ** <span class="html-italic">p</span> < 0.01; *** <span class="html-italic">p</span> < 0.001).</p> "> Figure 10
<p><b>A single dose of CORAVAX immunization induces antibody-dependent cellular cytotoxicity activity.</b> Antibody-dependent cellular cytotoxicity (ADCC) activation activity luciferase reporter assay. Vero cells infected with a Measles virus-expressing full SARS-CoV-2 spike protein were incubated with hamster sera and then incubated with effector cells (mouse FcγRIV-expressing Jurkat cells at a ratio of 5:1 (effector to target)). Heat-inactivated pooled sera were used for the assay. The CORAVAX vaccine group is shown in blue circles, the FILORAB1 control group is in black triangles and fifteen days post-challenge hamster sera from a previous experiment is depicted with a grey multiplication sign. The figure represents one replicate of 3 repeats. Fold induction is depicted for each group.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Viruses
2.3. Cells
2.4. Vaccine Production and Purification
2.5. Vaccination and SARS-CoV-2 Challenge
2.6. Recombinant Proteins for ELISA
2.7. Enzyme-Linked Immunosorbent Assay
2.8. SARS-CoV-2 Neutralizing Antibody Response
2.9. Rabies Virus Neutralization by RFFIT
2.10. Tissue Processing
2.11. Viral Load Determination
2.12. Viral RNA Copies by qRT-PCR
2.13. Cytokine qPCR
2.14. Histology
2.15. Antibody-Dependent Effector Functions
2.16. Statistical Analysis
3. Results
3.1. Immunogenicity of a Single Dose of CORAVAX in Syrian Hamsters
3.2. CORAVAX Induces Potent Immune Responses against RABV
3.3. A Single Dose of CORAVAX Protects the Hamsters from Weight Loss and Viral Burden in the Lungs Post-SARS-CoV-2 Challenge
3.4. A Single Dose of CORAVAX Can Significantly Reduce Lung Pathology in Hamsters
3.5. A Single Dose of CORAVAX Can Significantly Prevent SARS-CoV-2-Induced Cytokine Storm in the Lungs
3.6. A Single Dose of CORAVAX Induces Antibodies with Antibody-Dependent Cellular Cytotoxicity Activity
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ritchie, H.; Mathieu, E.; Rodés-Guirao, L.; Appel, C.; Giattino, C.; Ortiz-Ospina, E.; Hasell, J.; Macdonald, B.; Beltekian, D.; Dattani, S.; et al. Coronavirus Pandemic (COVID-19). Available online: https://ourworldindata.org/coronavirus (accessed on 2 December 2021).
- Kurup, D.; Schnell, M.J. SARS-CoV-2 vaccines—The biggest medical research project of the 21st century. Curr. Opin. Virol. 2021, 49, 52–57. [Google Scholar] [CrossRef]
- Khoury, D.S.; Cromer, D.; Reynaldi, A.; Schlub, T.E.; Wheatley, A.K.; Juno, J.A.; Subbarao, K.; Kent, S.J.; Triccas, J.A.; Davenport, M.P. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 2021, 27, 1205–1211. [Google Scholar] [CrossRef]
- Bajema, K.L.; Dahl, R.M.; Evener, S.L.; Prill, M.M.; Rodriguez-Barradas, M.C.; Marconi, V.C.; Beenhouwer, D.O.; Holodniy, M.; Lucero-Obusan, C.; Brown, S.T.; et al. Comparative Effectiveness and Antibody Responses to Moderna and Pfizer-BioNTech COVID-19 Vaccines among Hospitalized Veterans—Five Veterans Affairs Medical Centers, United States, 1 February–30 September 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 1700–1705. [Google Scholar] [CrossRef]
- Self, W.H.; Tenforde, M.W.; Rhoads, J.P.; Gaglani, M.; Ginde, A.A.; Douin, D.J.; Olson, S.M.; Talbot, H.K.; Casey, J.D.; Mohr, N.M.; et al. Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations among Adults without Immunocompromising Conditions—United States, March–August 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 1337–1343. [Google Scholar] [CrossRef]
- Sadoff, J.; Gray, G.; Vandebosch, A.; Cárdenas, V.; Shukarev, G.; Grinsztejn, B.; Goepfert, P.A.; Truyers, C.; Fennema, H.; Spiessens, B.; et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19. N. Engl. J. Med. 2021, 384, 2187–2201. [Google Scholar] [CrossRef]
- CDC. Johnson & Johnson’s Janssen COVID-19 Vaccine: Overview and Safety. Available online: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html (accessed on 1 December 2021).
- Liu, X.; Luongo, C.; Matsuoka, Y.; Park, H.-S.; Santos, C.; Yang, L.; Moore, I.N.; Afroz, S.; Johnson, R.F.; Lafont, B.A.P.; et al. A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters. Proc. Natl. Acad. Sci. USA 2021, 118, e2109744118. [Google Scholar] [CrossRef] [PubMed]
- Cohn, B.A.; Cirillo, P.M.; Murphy, C.C.; Krigbaum, N.Y.; Wallace, A.W. Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, 1 February 2021 to 13 August 2021. medRxiv 2021. [Google Scholar] [CrossRef]
- Frieman, M.; Harris, A.D.; Herati, R.S.; Krammer, F.; Mantovani, A.; Rescigno, M.; Sajadi, M.M.; Simon, V. SARS-CoV-2 vaccines for all but a single dose for COVID-19 survivors. EBioMedicine 2021, 68, 103401. [Google Scholar] [CrossRef]
- Kurup, D.; Wirblich, C.; Ramage, H.; Schnell, M.J. Rabies virus-based COVID-19 vaccine CORAVAX™ induces high levels of neutralizing antibodies against SARS-CoV-2. npj Vaccines 2020, 5, 98. [Google Scholar] [CrossRef] [PubMed]
- Kurup, D.; Fisher, C.R.; Scher, G.; Yankowski, C.; Testa, A.; Keshwara, R.; Abreu-Mota, T.; Lambert, R.; Ferguson, M.; Rinaldi, W.; et al. Tetravalent Rabies-Vectored Filovirus and Lassa Fever Vaccine Induces Long-term Immunity in Nonhuman Primates. J. Infect. Dis. 2021, 224, 995–1004. [Google Scholar] [CrossRef] [PubMed]
- Kurup, D.; Malherbe, D.C.; Wirblich, C.; Lambert, R.; Ronk, A.J.; Diba, L.Z.; Bukreyev, A.; Schnell, M.J. Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model. PLoS Pathog. 2021, 17, e1009383. [Google Scholar] [CrossRef] [PubMed]
- Kurup, D.; Fisher, C.; Smith, T.G.; Mota, T.A.; Yang, Y.; Jackson, F.R.; Gallardo-Romero, N.; Franka, R.; Bronshtein, V.; Schnell, M.J. Inactivated Rabies Virus–Based Ebola Vaccine Preserved by Vaporization Is Heat-Stable and Immunogenic Against Ebola and Protects Against Rabies Challenge. J. Infect. Dis. 2019, 220, 1521–1528. [Google Scholar] [CrossRef] [PubMed]
- Aleebrahim-Dehkordi, E.; Molavi, B.; Mokhtari, M.; Deravi, N.; Fathi, M.; Fazel, T.; Mohebalizadeh, M.; Koochaki, P.; Shobeiri, P.; Hasanpour-Dehkordi, A. T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses. Transpl. Immunol. 2022, 70, 101495. [Google Scholar] [CrossRef] [PubMed]
- Shou, S.; Liu, M.; Yang, Y.; Kang, N.; Song, Y.; Tan, D.; Liu, N.; Wang, F.; Liu, J.; Xie, Y. Animal Models for COVID-19: Hamsters, Mouse, Ferret, Mink, Tree Shrew, and Non-human Primates. Front. Microbiol. 2021, 12, 626553. [Google Scholar] [CrossRef]
- Kojima, N.; Klausner, J.D. Protective immunity after recovery from SARS-CoV-2 infection. Lancet Infect. Dis. 2021, 22, 12–14. [Google Scholar] [CrossRef]
- Townsend, J.P.; Hassler, H.B.; Wang, Z.; Miura, S.; Singh, J.; Kumar, S.; Ruddle, N.H.; Galvani, A.P.; Dornburg, A. The durability of immunity against reinfection by SARS-CoV-2: A comparative evolutionary study. Lancet Microbe 2021, 2, e666–e675. [Google Scholar] [CrossRef]
- Goldberg, Y.; Mandel, M.; Bar-On, Y.M.; Bodenheimer, O.; Freedman, L.; Ash, N.; Alroy-Preis, S.; Huppert, A.; Milo, M. Protection and waning of natural and hybrid COVID-19 immunity. medRxiv 2021. [Google Scholar] [CrossRef]
- Altmann, D.M.; Boyton, R.J. Waning immunity to SARS-CoV-2: Implications for vaccine booster strategies. Lancet Respir. Med. 2021, 9, 1356–1358. [Google Scholar] [CrossRef]
- Kent, S.J.; Juno, J.A. Vaccination after prior COVID-19 infection: Implications for dose sparing and booster shots. eBioMedicine 2021, 72, 103586. [Google Scholar] [CrossRef]
- Callaway, E. COVID super-immunity: One of the pandemic’s great puzzles. Nature 2021, 598, 393–394. [Google Scholar] [CrossRef]
- Falsey, A.R.; Sobieszczyk, M.E.; Hirsch, I.; Sproule, S.; Robb, M.L.; Corey, L.; Neuzil, K.M.; Hahn, W.; Hunt, J.; Mulligan, M.J.; et al. Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) COVID-19 Vaccine. N. Engl. J. Med. 2021, 385, 2348–2360. [Google Scholar] [CrossRef] [PubMed]
- Baker, A.T.; Boyd, R.J.; Sarkar, D.; Teijeira-Crespo, A.; Chan, C.K.; Bates, E.; Waraich, K.; Vant, J.; Wilson, E.; Truong, C.D.; et al. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Sci. Adv. 2021, 7, eabl8213. [Google Scholar] [CrossRef] [PubMed]
- Crea, F. Thrombosis in peripheral artery disease and thrombotic thrombocytopenia after adenoviral COVID-19 vaccination. Eur. Heart J. 2021, 42, 3995–3999. [Google Scholar] [CrossRef] [PubMed]
- Misasi, R.; Capozzi, A.; Riitano, G.; Recalchi, S.; Manganelli, V.; Mattei, V.; Longo, A.; De Michele, M.; Garofalo, T.; Pulcinelli, F.M.; et al. Signal transduction pathway involved in platelet activation in immune thrombotic thrombocytopenia after COVID-19 vaccination. Haematologica 2021, 107, 326–329. [Google Scholar] [CrossRef]
- Hwang, J.; Park, S.H.; Lee, S.W.; Lee, S.B.; Lee, M.H.; Jeong, G.H.; Kim, M.S.; Kim, J.Y.; Koyanagi, A.; Jacob, L.; et al. Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: The FAPIC score. Eur. Heart J. 2021, 42, 4053–4063. [Google Scholar] [CrossRef]
- Mohseni Afshar, Z.; Babazadeh, A.; Janbakhsh, A.; Afsharian, M.; Saleki, K.; Barary, M.; Ebrahimpour, S. Vaccine-induced immune thrombotic thrombocytopenia after vaccination against COVID-19: A clinical dilemma for clinicians and patients. Rev. Med. Virol. 2021, 32, e2273. [Google Scholar] [CrossRef]
- Rzymski, P.; Perek, B.; Flisiak, R. Thrombotic Thrombocytopenia after COVID-19 Vaccination: In Search of the Underlying Mechanism. Vaccines 2021, 9, 559. [Google Scholar] [CrossRef]
- Costello, A.; Pandita, A.; Devitt, J. Case Report: Thrombotic Thrombocytopenia after COVID-19 Janssen Vaccination. Am. Fam. Physician 2021, 103, 646–647. [Google Scholar]
- Toback, S.; Galiza, E.; Cosgrove, C.; Galloway, J.; Goodman, A.L.; Swift, P.A.; Rajaram, S.; Graves-Jones, A.; Edelman, J.; Burns, F.; et al. Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: An exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial. Lancet Respir. Med. 2021, 10, 167–179. [Google Scholar] [CrossRef]
- Heath, P.T.; Galiza, E.P.; Baxter, D.N.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D.R.; Clark, R.; Cosgrove, C.; Galloway, J.; et al. Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine. N. Engl. J. Med. 2021, 385, 1172–1183. [Google Scholar] [CrossRef]
- The Novavax Vaccine against COVID-19: What You Need to Know. Available online: https://www.who.int/news-room/feature-stories/detail/the-novavax-vaccine-against-covid-19-what-you-need-to-know (accessed on 21 December 2021).
- Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Wang, P.; Nair, M.S.; Yu, J.; Rapp, M.; Wang, Q.; Luo, Y.; Chan, J.F.; Sahi, V.; Figueroa, A.; et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 2020, 584, 450–456. [Google Scholar] [CrossRef] [PubMed]
- Poland, G.A.; Ovsyannikova, I.G.; Kennedy, R.B. SARS-CoV-2 immunity: Review and applications to phase 3 vaccine candidates. Lancet 2020, 396, 1595–1606. [Google Scholar] [CrossRef]
- Centers for Disease Control and Prevention; National Center for Emerging and Zoonotic Infectious Diseases. Precautions or Contraindications for Rabies Vaccination. Available online: https://www.cdc.gov/rabies/specific_groups/hcp/vaccination_precautions.html (accessed on 7 February 2022).
- A Phase 1, Open Label, Dose Escalation, Randomized, Multicenter Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of an Intramuscular Inactivated Rabies Vector Platform Corona Virus Vaccine (rDNA-BBV151) in Healthy Volunteers. Available online: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=58694&EncHid=&userName=BBV151 (accessed on 16 August 2021).
- Lee, A.C.; Zhang, A.J.; Chan, J.; Li, C.; Fan, Z.; Liu, F.; Chen, Y.; Liang, R.; Sridhar, S.; Cai, J.; et al. Oral SARS-CoV-2 Inoculation Establishes Subclinical Respiratory Infection with Virus Shedding in Golden Syrian Hamsters. Cell Rep. Med. 2020, 1, 100121. [Google Scholar] [CrossRef]
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Kurup, D.; Wirblich, C.; Zabihi Diba, L.; Lambert, R.; Watson, M.; Shaikh, N.; Ramage, H.; Solomides, C.; Schnell, M.J. A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model. Viruses 2022, 14, 1126. https://doi.org/10.3390/v14061126
Kurup D, Wirblich C, Zabihi Diba L, Lambert R, Watson M, Shaikh N, Ramage H, Solomides C, Schnell MJ. A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model. Viruses. 2022; 14(6):1126. https://doi.org/10.3390/v14061126
Chicago/Turabian StyleKurup, Drishya, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, and Matthias J. Schnell. 2022. "A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model" Viruses 14, no. 6: 1126. https://doi.org/10.3390/v14061126