577. COVI-VAC™, a Live Attenuated COVID-19 Vaccine, Provides Single Dose Protection Against Heterologous Challenge with SARS-CoV-2 Beta (B.1.351) in the Syrian Golden Hamster Model

Abstract Background Although multiple COVID-19 vaccines are currently in use, emergence of novel SARS-CoV-2 variants with reduced neutralization raises concern of future vaccine escape. COVI-VAC™ is a live attenuated SARS-CoV-2 strain based on WA/1 being developed as an intranasal COVID-19 vaccine. COVI-VAC is attenuated through removal of the furin cleavage site and introduction of 283 silent, deoptimizing mutations that maintain viral amino acid sequence but slow viral replication in vivo by up to 5 logs. Notably, COVI-VAC presents all viral antigens in their native conformation and is not limited to spike. COVI-VAC demonstrated attenuation, immunogenicity and single dose protection in both the Syrian golden hamster and non-human primate models and currently in Phase 1 clinical trials. In this study, we evaluated efficacy of COVI-VAC against challenge with the Beta/B.1.351 variant in Syrian golden hamsters. Methods Syrian golden hamsters, 7-10 weeks of age were, vaccinated intranasally with 8.25x104 PFU COVI-VAC (n=28) or vehicle control (n=16). Twenty seven days post-vaccination, animals were challenged intranasally with 3x104 PFU of wildtype (WT) SARS-CoV-2 Beta. Animals were weighed daily. Further analysis is being conducted with serum and key tissues from pre and post challenge timepoints to include neutralizing antibody, biodistribution (subgenomic qPCR) and histopathology. Results COVI-VAC prevented weight loss following challenge with the heterologous variant of SARS-CoV-2, B.1.351/Beta (Figure). Results of additional analyses will be available before the IDWeek meeting. Change in Weight following SARS-CoV-2 Beta Challenge Conclusion COVI-VAC is protective against heterologous challenge with SARS-CoV-2 Beta. By presenting all viral antigens, COVI-VAC may be less affected by viral evolution than spike-based vaccines. Disclosures Anna Kushnir, PHD, Codagenix Inc (Employee) Steffen Mueller, PhD, Codagenix Inc (Board Member, Employee, Shareholder) Sybil Tasker, MD, MPH, FIDSA, Codagenix Inc (Employee, Shareholder) J. Robert Coleman, PhD, Codagenix Inc. (Board Member, Employee, Shareholder)

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A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0007462 ◽

2019 ◽

Vol 13 (6) ◽

pp. e0007462 ◽

Cited By ~ 15

Author(s):

Neeltje van Doremalen ◽

Teresa Lambe ◽

Sarah Sebastian ◽

Trenton Bushmaker ◽

Robert Fischer ◽

...

Keyword(s):

Single Dose ◽

Complete Protection ◽

Golden Hamsters ◽

Syrian Golden Hamsters ◽

Vectored Vaccine

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Methylated purines in the deoxyribonucleic acid of various Syrian-golden-hamster tissues after administration of a hepatocarcinogenic dose of dimethylnitrosamine

Biochemical Journal ◽

10.1042/bj1570627 ◽

1976 ◽

Vol 157 (3) ◽

pp. 627-634 ◽

Cited By ~ 69

Author(s):

G P Margison ◽

J M Margison ◽

R Montesano

Keyword(s):

Acid Hydrolysis ◽

Golden Hamster ◽

Deoxyribonucleic Acid ◽

Syrian Golden Hamster ◽

Mild Acid Hydrolysis ◽

Liver Tumours ◽

Purine Bases ◽

Syrian Golden Hamsters ◽

Mild Acid ◽

Lung And Kidney

1. DNA was extracted from livers, kidneys and lungs of Syrian golden hamsters at various times (up to 96h) after injection of a hepatocarcinogenic dose of [14C]dimethylnitrosamine. Purine bases were released from the DNA by mild acid hydrolysis and separated by Sephadex G-10 chromatography. 2. At 7h after dimethylnitrosamine administration liver DNA was alkylated to the greatest extent, followed by that of lung and kidney, the values for which were 8 and 3% respectively of those for liver. 3. The O6-methylguanine/7-methylguanine ratios were initially the same in all three organs and in the liver DNA of rats under similar conditions of dose. 4. O6-Methylguanine was the most persistent alkylated purine in all three hamster tissues. There was evidence for excision of 7-methyl-guanine, the highest activity for this being present in the liver. 5. Detectable amounts of the minor products 3-methyladenine, 1-methyladenine, 3-methylguanine and 7-methyladenine were present in most hamster tissues, and their individual rates of loss from liver DNA were determined. 6. Ring-labelling of the normal purines in DNA was highest in the liver, followed closely by the lung (80% of that in liver) whereas the kidney had very low incorporation (3% of that in liver). 7. The results are discussed with respect to the hepatotoxicity of dimethylnitrosamine, the miscoding potential of the various alkylation products and the induction of liver tumours in hamsters.

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Differential Modification of Development of Preneoplastic Lesions in the Syrian Golden Hamster Initiated With a Single Dose of 2,2′-Dioxo-N-nitrosodipropylamine: Influence of Subsequent Butylated Hydroxyanisole, α-Tocopherol, or Carbazole23

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/78.2.289 ◽

1987 ◽

Keyword(s):

Single Dose ◽

Golden Hamster ◽

Syrian Golden Hamster ◽

Butylated Hydroxyanisole ◽

Preneoplastic Lesions

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Investigations on the carcinogenic burden by air pollution in man the effect of a single dose of benzo(a)pyrene in Syrian golden hamsters

Cancer Letters ◽

10.1016/s0304-3835(77)95980-8 ◽

1977 ◽

Vol 3 ◽

pp. 231-235 ◽

Cited By ~ 2

Author(s):

Madhukar Ketkar ◽

Gerd Reznik ◽

Jurgen Misfeld ◽

Ulrich Mohr

Keyword(s):

Air Pollution ◽

Single Dose ◽

Golden Hamsters ◽

Syrian Golden Hamsters

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A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters

10.1101/2021.06.16.448525 ◽

2021 ◽

Author(s):

Kathryn McGuckin Wuertz ◽

Erica Barkei ◽

Wei-hung Chen ◽

Elizabeth J. Martinez ◽

Ines Elakhal Naouar ◽

...

Keyword(s):

Neutralizing Antibody ◽

High Dose ◽

Lung Pathology ◽

Vaccine Protection ◽

Golden Hamsters ◽

Heterologous Challenge ◽

Syrian Golden Hamsters ◽

Antibody Titers ◽

Binding Antibody ◽

Adequate Coverage

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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