Neutralising antibodies prevent PRRS viremia rebound: evidence from a data-supported model of immune response

Natacha Go 1, 2, 3 Suzanne Touzeau 1, 4 Catherine Belloc 2 Andrea Doeschl-Wilson 3
1 BIOCORE - Biological control of artificial ecosystems
INRA - Institut National de la Recherche Agronomique, CRISAM - Inria Sophia Antipolis - Méditerranée , LOV - Laboratoire d'océanographie de Villefranche
Abstract : Understanding the mechanisms determining the variability in infection dynamics between hosts or strains for a given pathogen is a key issue to better understand and control infection spread. In particular, effective and constant reduction in pathogen load is desirable over infection profiles exhibiting rebounds for the health of the infected individuals and the entire herd. In this context, PRRS virus is of a particular interest. Indeed, (i) infection profiles either with or without rebound have been reported for various viral strains and host breeds; (ii) mechanisms responsible for the emergence of rebounds are unclear; (iii) PRRS virus infections are associated with highly variable global immune responses and mechanisms responsible for the infection dynamics are still poorly understood. We aimed at identifying immune mechanisms that could explain PRRSv infection rebounds using a mathematical modelling approach of the within-host dynamics. Compared to published immunological models, our model provides both an integrative and detailed view of the immune response, representing the mechanisms at the between-cell scale. We fitted the model to a set of viremia data following an experimental challenge of 240 pigs with the same dose of a virulent PRRS virus strain resulting in both rebounder (109) and non-rebounder (131) profiles. Within a profile, experimental data exhibited a wide between-host variability in infection dynamics. Between both profiles, the variability in infection dynamics preceding the rebound (i.e. during the first 20 days of the 42-day post inoculation observation period) was similar. We compared, between rebounders and non-rebounders, the set of estimated parameter values, the resulting immune dynamics and the activation levels of the underlying immune mechanisms. The activation levels were quantified by the cumulated number of viral particles or infected cells that were created or destroyed over the infection time (i.e. the flows) by mechanisms of interest: viral replication, phagocytosis of viral particles, cell infection, viral neutralisation, cytolysis (by natural killers and cytotoxic lymphocytes) and apoptosis (by TNFα antiviral cytokine) of infected cells. Compared to non-rebounders, rebounders were characterised by a higher level of immune response activation, due to higher rates of cell infection. They also exhibited higher flows of infected cell cytolysis and apoptosis, but similar viral neutralisation flows despite higher infection and viral replication flows. This points out an inadequate production of neutralising antibodies. These results would suggest that vaccines or genetic selection promoting a strong neutralising response, ideally associated with strong antiviral and cytolytic responses, should prevent against infection with rebound.
Type de document :
Communication dans un congrès
ModAH 2017 - Modelling in Animal Health conference , Jun 2017, Nantes, France. 〈https://workshop.inra.fr/modah2017/〉
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https://hal.inria.fr/hal-01577647
Contributeur : Jean-Luc Gouzé <>
Soumis le : dimanche 27 août 2017 - 11:15:13
Dernière modification le : mercredi 19 septembre 2018 - 01:18:48

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  • HAL Id : hal-01577647, version 1

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Natacha Go, Suzanne Touzeau, Catherine Belloc, Andrea Doeschl-Wilson. Neutralising antibodies prevent PRRS viremia rebound: evidence from a data-supported model of immune response. ModAH 2017 - Modelling in Animal Health conference , Jun 2017, Nantes, France. 〈https://workshop.inra.fr/modah2017/〉. 〈hal-01577647〉

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