Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mouse and non-human primates

Abstract

SummaryThe SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

An AAV-ie based Vaccine effectively protects against SARS-CoV-2 and Circulating Variants

“…However, whether this vaccine avoids mutational immune escapes remains unclear. 19 Our results suggest that S1 is a better immunogen for SARS-CoV-2 vaccine development than the full-length S protein. AAV-ie-S1 vaccine showed several advantages, such as thermostability, high efficiency, safety, and single-dose vaccination.…”

Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination

“…The preclinical safety and immunogenicity of two novel AAV vector-based COVID-19 vaccines were recently reported. 156 In this particular study, AAVrh32.33, a novel vector developed from rhesus macaques isolates with highly reduced antibody prevalence in humans, 157 was utilized to express a full-length SARS-CoV-2 S protein locked in a prefusion conformation and a truncated version of SARS-CoV-2 S protein designed to be secreted. Both vaccine candidates manifested robust long-lived humoral and cellular immunogenic responses following a single intramuscular injection in rodents and nonhuman primates.…”

Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches

“…This strategy could obtain a fast protection against the virus, even in subjects with weakened immune system, since the antibodies would be directly produced by cells in the respiratory tract, not the lymphocytes [4]. In another approach, AAVs could be designed to express critical domains of the SARS-CoV-2 Spike protein [5], following the strategy of the first generation of adenovirus-based vaccines. In this case, the high thermal stability of AAV particles facilitates the logistics of global vaccination campaigns, by alleviating the need of a highly demanding cold chain in areas with weak civil infrastructures.…”

“…This would have potential implications for patients with genetic disorders who could benefit from gene therapies, often coming in the form of AAV-based vectors. The good news is that the repertoire of AAVs is remarkably wide, and careful selection can identify candidates with optimal properties as vaccines and low risk of cross-reactivity with commonly used gene therapy vectors [5].…”