In recent years a new generation of vaccines has emerged as promising alternative to conventional vaccines. In the field of influenza vaccines production those developed through RNA platforms have demonstrated potent immunogenicity in preclinical models and offer numerous benefits in terms of both safety and efficacy. One of the primary goals of these vaccines is to create products able to offer a broader and longer-lasting protection against influenza viruses, which undergo antigenic changes every year. In fact, the vaccines currently in use despite substantial improvements show varying level of protection against seasonal influenza strains and do not allow a rapid response in case of pandemic emergencies. In the preclinical development phase of an influenza vaccine, among animal species susceptible to the influenza virus, ferrets (Mustela putorius f.furo) are one of the best small models for the study of virus pathogenesis. In this work, the ferrets were a useful model to study a new generation of vaccines based on mRNA encoding HA antigen from influenza strains. Three preclinical studies were conducted to evaluate various aspects of these vaccines. One of the aims of this research was to demonstrate that these vaccines can induce a heterologous immune response in ferrets vaccinated with a quadrivalent mRNA vaccine containing different concentrations of immunizing molecule. Antibody response was evaluated for the antigenic variant of subtype H3N2 (A /Hong Kong /4801/2014), contained in the 2016/2017 seasonal vaccine, and for those of the past seasons. Another objective was to evaluate different mRNA vaccine formulations to understand the better one. The results were compared to the antibody response given by a traditional subunit influenza vaccine containing an adjuvant. In one of three studies, 48 ferrets immunized with different vaccines were divided into groups and some were pre-exposed to an H3N2 virus while others were not. The antibody response against the main antigenic protein of the four strains contained in the mRNA vaccines used for immunization was evaluated. Serum samples were analyzed by serological assays for antibody detection. An Hemagglutination Inhibition (HI) assay, a method recognized by the regulatory agency EMA (European Medicine Agency) for the release of flu vaccines was performed following the protocol of the WHO (World Health Organization). To confirm the data obtained the Micro Neutralization (MN) assay was performed on the same samples, using live virus and based on the identification of the cytopathic effect in vitro (MN CPE-based). Preclinical data showed good immunogenicity, especially to HA of H3N2, and good heterologous immune response.
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|Titolo:||VACCINI INFLUENZALI DI NUOVA GENERAZIONE: STUDI PRECLINICI IN MODELLI ANIMALI|
|Citazione:||Maggetti, M. (2019). VACCINI INFLUENZALI DI NUOVA GENERAZIONE: STUDI PRECLINICI IN MODELLI ANIMALI.|
|Appare nelle tipologie:||8.1 Tesi Dottorato|