Défense de thèse de doctorat en sciences vétérinaires

Evaluation of immune responses induced by vectored recombinant HVT vaccines using Gumboro disease as a model

Jury

Nicolas ETERRADOSSI (ANSES, Ploufragan), Gwenaëlle DAUPHIN (FAO et CERVA Santé animale, Italy), Laurent GILLET (ULg), Thierry VAN DEN BERG (Coda-Cerva, Bruxelles), Bénédicte LAMBRECHT, promoteur (Coda-Cerva, Bruxelles), Xavier DE BOLLE, président (UNamur), Jean-Jacques LETESSON (UNamur), Benoît MUYLKENS, promoteur (UNamur)

Résumé

Herpesvirus of turkey (HVT) is a nonpathogenic alphaherpesvirus commonly used in chicken as a vaccine against Marek’s disease (MD) because of its antigenic relationship with MD virus, but also as an efficient recombinant (rHVT) vaccine into which foreign genes coding for protective antigens are inserted and subsequently expressed. These bivalent vaccines are widely recognized as safe and efficacious against several avian pathologies. The present study primarily focused on infectious bursal disease (IBD), also called Gumboro disease, which is an immunosuppressive avian pathology that represents a major threat in many developing countries. The economic impact of IBD, and the drawbacks carried by classical vaccines, have required the development of new generation vaccines like rHVT. The latter express the immunogenic VP2 protein of IBDV (rHVT-IBD), and have been licensed for in ovo and day-old immunization of commercial chickens.

In this thesis, we first analyzed the expression of VP2 by rHVT-IBD vaccines, and have shown that the viral gene is detectable in situ following day-old vaccination. These findings highlight a rapid widespread distribution of rHVT-IBD throughout host tissues, and an increased rHVT-IBD genome load in the feather follicles of vaccinated chickens. Thus far, however, there is little knowledge available regarding the interactions of rHVT-IBD, with the host immune system, and the immune mechanisms involved in the stimulation of protective immunity.  Although humoral immunity is considered to play an essential role in protection against IBD, low levels of anti-VP2 antibodies are detected following rHVT-IBD vaccination, suggesting the probable role played by cell-mediated immunity (CMI). Despite the increasing availability of tools to measure cellular responses in chicken, the contribution of vaccines-associated CMI is still poorly documented. In this context, we investigated the immune responses triggered by rHVT-IBD vaccines in the host, and demonstrated that IBDV-specific CMI could be measured from 3 weeks post-vaccination. Furthermore, early cytotoxic responses to rHVT-IBD immunization were demonstrated to be triggered. To determine the contribution of these responses in the initiation of immunity against IBDV without using tedious classical CTL assays, we developed an experimental in vivo model to stimulate IBDV-specific immune responses. The rapid viral clearance associated with the increased expression of genes related to adaptive immunity suggest that IBDV-specific cellular responses are stimulated within the first two weeks following immunization with rHVT-IBD. Although our approach exhibited methodological limitations indicating that there is still room for improvement, this in vivo model yielded encouraging results assessing the feasibility of evaluating virus-specific cellular responses. Such approach could be useful in characterizing T-cell responses in rHVT-vaccinated chickens submitted to an infectious challenge.

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