Protective immune responses elicited after consecutive inoculations of the same antigen, using different vaccine delivery approaches

ROMANUTTI CARINA; D'ANTUONO ALEJANDRA; PALACIOS CARLOS; QUATTROCCHI VALERIA; ZAMORANO PATRICIA; LA TORRE JOSE; MATTION NORA

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Conferencia; Open sessions of the standing technical and research committees of the EuFMD commission; 2012

The European Commission for the control of Foot-and-Mouth disease (EuFMD)

Introduction: New generation vaccines against foot-and-mouth disease virus (FMDV) have been largely explored, though they have not equaled the efficacy of the conventional killed virus vaccine in use. In the present study, we analyzed the immune responses elicited by consecutive immunizations of the same antigen, using different vaccine delivery approaches, in a heterologous prime?boost format. Materials and Methods: Herpesvirus and adenovirus vectors encoding FMDV structural proteins and the 3C protease from O1 Campos strain, and inactivated oil adjuvanted O1 Campos virus were used in a heterologous prime-boost schedule. Humoral and cellular immunity and protection after challenge in BALB/c mice was used. Results: The magnitude and duality of the protective immune response was dependent on the delivery immunization regimen used. Priming with any of the viral vectors induced a shift of the cytokine balance towards a Th1 type immune response, with a IgG1/IgG2a ratio of 0.5-0.8, regardless of the delivery system used for boosting, while priming with inactivated virus induced a Th2 type response, with a ratio IgG1/IgG2a=1.5.  Heterologous prime-boost induced significantly higher specific antibody titers than homologous booster immunization (p< 0.05).  Interestingly, similar antibody titers were elicited in mice vaccinated with heterologous combinations including viral vectors, than in mice that received two doses of adjuvanted killed virus. Re-stimulation of mice with inactivated virus after 146 days resulted in a fast increase of antibody titers and memory B cells in all groups. In challenge experiments, after priming of the animals with the adenovirus viral vector, boosting with herpesvirus amplicons or killed virus induced 75% protection, the same percentage obtained with two doses of oil adjuvanted inactivated virus. Discussion: Immunization with viral vector-based vaccines combined with protein-based vaccines in diverse delivery formats may represent a promising approach for improving active protection against FMDV.