Phase I clinical trials of safety and immunogenicity of live cultural influenza vaccine vector-flu

Abstract

Background Live influenza vaccines trigger all major components of the anti-flu immune response machinery and have been included in the global WHO program on the pandemic preparedness. Key advantages of using live vaccines include a feasibility of intranasal administration, opportunity to rapidly scale up production of the viral substance, simplicity of vaccination, and robust protection against antigenic drift variants of the virus. Use of certified cell cultures for the cultivation of seasonal strains of influenza along with biodegradable materials for constructing delivery vehicles is considered one of the mainstream approaches to the development of new generations of flu vaccines. We developed a live cultural influenza vaccine called Vector-Flu, which is based on the cold-adapted virus strain A/17/California/2009/38 (H1N1) and MDCK cell line obtained from the certified cell culture depository. Preclinical studies have demonstrated safety and high immunogenicity of Vector-Flu in a ferret model. Phase I of clinical trials was conducted on healthy volunteers in the Medical Unit #163 in Koltsovo, Russia. The trial pursued the following goals:1) Evaluation of safety and tolerability.2) Evaluation of the humoral and adaptive immune response using HI, ELISA and microneutralization assay.3) Evaluation of the cellular immune response, as measured by the cytokine release level in response to the ex vivo stimulation of blood lymphocytes by the influenza virus. Materials and methods Cell culture MDCK from Cell Culture Collection of SRC VB VECTOR. Cells were passed in serum-free SFM4MegaVir medium (USA). The characteristics of the MDCK cell line were studied in accordance with WHO [1].