P31-08 Evaluation of Repeated-Dose Toxicity and Safety of a Plant-Derived SARS-CoV-2 S1 Vaccine in New Zealand White Rabbits

The continuous emergence of various SARS-CoV-2 variants, including Omicron sublineages, underscores the need for COVID-19 vaccines that offer broad and lasting immunogenicity. Bivalent and multivalent vaccines have shown promise in improving protection, but the waning immunity over time necessitates the administration of strategic boosters to maintain efficacy. Transgenic plants, such as Nicotiana benthamiana , engineered to express vaccine antigens like SARS-CoV-2 S1, provide a rapid, scalable, and cost-effective platform for antigen production, offering a safer alternative to traditional cell-based expression systems. This study aimed to assess the repeated-dose toxicity of a plant-derived SARS-CoV-2 S1 vaccine in New Zealand White (NZW) rabbits to evaluate its safety. The vaccine, which was formulated as an emulsion combining the SARS-CoV-2 S1 antigen and a synthetic TLR4 agonist, was administered intramuscularly four times over a period of 9 weeks, followed by a 4-week recovery phase. Experimental groups included the vehicle, vaccine, adjuvant, and a combination of vaccine and adjuvant. Following GLP guidelines, a comprehensive set of parameters was evaluated, including mortality, clinical signs, body weight, food consumption, skin irritation, body temperature, ophthalmologic assessments, urinalysis, organ examination, organ weights, hematological analysis, serum biochemistry, histopathology, and immunogenicity. The results revealed no significant adverse effects in any of the experimental groups. However, some changes in hematology and clinical chemistry were observed, including increased neutrophil and monocyte counts in the vaccine group. These changes were generally reversible after the recovery period and were not considered to be toxicologically significant. In conclusion, the plant-derived SARS-CoV-2 S1 vaccine demonstrated no significant adverse effects in New Zealand White rabbits, with any observed hematological and clinical chemistry changes being reversible and not toxicologically relevant. These findings suggest that the vaccine is a promising candidate for further development as a safe and effective solution for COVID-19.