A linear DNA encoding the SARS-CoV-2 receptor binding domain elicits potent immune response and neutralizing antibodies in domestic cats

Antonella Conforti; Elisa Sanchez; Erika Salvatori; Lucia Lione; Mirco Compagnone; Eleonora Pinto; Fabio Palombo; Emanuela D'Acunto; Alessia Muzi; Giuseppe Roscilli; Yuhua Sun; Brian Viscount; James Hayward; Clay Shorrock; Diego G Diel; Joseph A Impellizeri; Luigi Aurisicchio

doi:10.1016/j.omtm.2022.12.015

A linear DNA encoding the SARS-CoV-2 receptor binding domain elicits potent immune response and neutralizing antibodies in domestic cats

Mol Ther Methods Clin Dev. 2023 Mar 9:28:238-248. doi: 10.1016/j.omtm.2022.12.015. Epub 2023 Jan 2.

Authors

Antonella Conforti^{1

2}, Elisa Sanchez³, Erika Salvatori¹, Lucia Lione¹, Mirco Compagnone⁴, Eleonora Pinto¹, Fabio Palombo^{1

4}, Emanuela D'Acunto¹, Alessia Muzi¹, Giuseppe Roscilli¹, Yuhua Sun^{5

6}, Brian Viscount^{5

6}, James Hayward^{5

6}, Clay Shorrock^{5

6}, Diego G Diel⁷, Joseph A Impellizeri³, Luigi Aurisicchio^{1

2

4}

Affiliations

¹ Takis Biotech, Via Castel Romano 100, 00128 Rome, Italy.
² Evvivax Biotech, Via Castel Romano 100, 00128 Rome, Italy.
³ Veterinary Oncology Services (VOS), PLLC, New York, NY, USA.
⁴ Neomatrix Biotech, Via Castel Romano 100, 00128 Rome, Italy.
⁵ Applied DNA Sciences, Inc., 50 Health Sciences Drive, Stony Brook, NY 11790, USA.
⁶ LineaRx, Inc., 50 Health Sciences Drive, Stony Brook, NY 11790, USA.
⁷ Department of Population Medicine and Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a clinical trial conducted in domestic cats to assess safety and immunogenicity of a linear DNA (linDNA) vaccine encoding the receptor-binding domain (RBD) from SARS-CoV-2 (Lin-COVID-eVax). Lin-COVID-eVax proved to be safe, with no significant adverse events, and was able to elicit both RBD-specific antibodies and T cells. Also, the linDNA vaccine induced neutralizing antibody titers against ancestral SARS-CoV-2 virus and its variants. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans.

Keywords: DNA vaccine; PCR; SARS-CoV-2; amplicons; cats.