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Towards an exploration of PRRSv vaccine efficiency in silico
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Poster. International audience. ntroduction:below: Vaccination is the main control strategy against the Porcine Respiratory and Reproductive Syndromevirus (PRRSv), a major concern of the swine industry. However, none commercial vaccine is efficient toeradicate the infection mainly because they only confer a partial protection of the host. Moreover,PRRSv exhibits a high virulence variability among strains and current vaccines provide only a partialcross-protection. Consequently, improving vaccine efficiency at the host level is still a major challengefor PRRS control. The immune mechanisms involved in vaccination and determining the hostprotection are not yet fully identified and seem variable among PRRSv strains. Considering thisvariability context and the complexity of immune mechanisms, we chose a modelling approach totackle this issue. We focused on modified-live vaccines, as they are assumed to be the more efficientagainst PRRSv.Materials and Methods:From the literature review of PRRSv immune dynamics, we developed an original model of the PRRSvwithin-host dynamics representing the immune mechanisms at the between-cell scale. This modeldescribes the evolution over time of (i) the within-host viral load and (ii) the major immune components(involved in the PRRSv-target cell interactions, the innate response, the adaptive response orientationand the cytokine regulations). We used this model to simulate a PRRSv infection of a vaccinated pig(i.e. starting with memory response, 2 levels of memory activation has been tested) considering bothPRRSv virulence (3 levels: low, reference and high) and exposure (3 intensities x 2 durations)variabilities.Results:Our results exhibited a clear vaccination efficiency to reduce the infection duration, whatever the strainvirulence and the exposure, but no efficiency on either the infection severity (characterised by the areaunder the curve of the viral titer) or the viral peak.The higher the memory activation level and the virulence level, the higher the vaccine efficiency. Theinnate mechanisms (phagocytosis, cell infection, viral replication) were not involved in the vaccinationefficiency. The adaptive response orientation associated with the infection duration decreases exhibiteda high variability depending on virulence and exposure level. High vaccine efficiency was globallyassociated with high levels of regulatory response. Finally, the higher the cytolysis and neutralisationactivities the higher the infection duration decreases due to vaccination.Conclusion:We proposed an original and adapted method to explore the efficiency of vaccination strategies. Ourresults provide insights to improve the vaccination efficiency, in particular regrading the adaptiveresponse orientation towards the regulatory. As we here considered a full cross-protection betweenviral strains, this model has to be adapted to take into account the genetic heterogeneity observed inthe field.
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