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Title: Characterization of the drug product HeberNasvac, a therapeutic vaccine against chronic hepatitis B

Matilde Lopez Abad

Center for Genetic Engineering and Biotechnology, Cuba

Biography

Matilde López Abad studied Chemical Engineering at University City José Antonio Echeverría (CUJAE), Cuba and graduated in 1997. She started working at the Center for Genetic Engineering and Biotechnology (CIGB) in the direction of Technological Development, in the group of Formulations Development with peptides and proteins as active ingredients. She received her MSc. degree in 2005 at the same institution. She is part of the author’s group of 2 patents and 7 research articles.

Abstract

HeberNasvac is a novel therapeutic vaccine for intranasal and subcutaneous administration in the treatment of chronic Hepatitis B. The immunological properties of this product have been demonstrated in mice models during the first stage of the product development and after that in different clinical stages, Phase I-III, demonstrating high safety and efficacy. This product contains the hepatitis B virus surface and nucleocapsid antigens (HBsAg and HBcAg) as active ingredient of the vaccine. Both antigens are virus-like particles (VLPs), and this characteristic constitutes a well established strategy in preventive vaccination. These non-infective particles have a composition, size, and structure favoring their interaction and processing by the immune system. In the drug product both antigens are formulated at a concentration of 0.1 mg/mL. The characterization of the aggregation level of the product was evaluated using several batches with different expiration dates. The analysis by Dynamic Light Scattering (DLS) showed the polydispersity of the samples. The particle size distribution was in the range between 20 and 180 nanometers (nm). The average size values between 43 and 61 nm. The Transmission electron microscopy (TEM) was used to analyze the morphology of the antigens particles and measure its size. In the HeberNasvac the antigens are able to agglomerate although the individual antigens conserve their specific morphology. The presence of subvisible particles was evaluated by the method of light obscuration. All the measures fulfilled the USP and EP pharmacopeia acceptance criteria for vaccine preparations (6000 particles or less in the range of less than 25 µm and 600 particles or less between 25 and 50 µm range). The immunogenicity of the product was evaluated under different experimental conditions and the induction of antibody response in the designed formulation was demonstrated. Real stability and accelerated studies showed the stability of the HeberNasvac for 36 months at 5 ± 3ºC and for 6 months at 25 ± 2ºC.
Audience take away:
• Knowledge about a new product against Hepatitis B containing virus-like particles obtained by biotechnology.
• Applied analytical techniques are exposed to the evaluation of the state of aggregation of the antigens in the pharmaceutical product.
• Designs for product characterization studies are evaluated.