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De Pasquale, C.

Publications and source records attributed to De Pasquale, C..

3 recordsLinked to original sources

Vaccination against H5 HP influenza virus leads to persistent immune response in wild king penguins

Since 2021, the panzootic of high pathogenicity avian influenza (HPAI) represents an increasing threat to wild vertebrate populations. In this context, recent vaccines developed for poultry could provide tools for the conservation of wild endangered birds populations. The king penguin (Aptenodytes patagonicus), a long-lived seabird breeding in dense colonies with an extended chick-rearing period, was identified as a possible surrogate species for a vaccination trial in a sub-Antarctic natural setting. We investigate here the immune response of king penguin chicks to a self-amplifying mRNA vaccine against a H5 HPAI clade 2.3.4.4b protein. Thirty chicks were vaccinated (primo- and boost-injections), 20 were kept as controls. Along 250 days of monitoring, vaccinated chicks showed a high and persistent immune response, granting a strong seroneutralisation capacity against the virus, up to fledging. No adverse effects were observed. The screening for antibodies against unspecific avian influenza viruses suggested that no natural infection occurred over the entire trial. The emergence of HPAI in the Southern Indian Ocean in October 2024 highlights the timeliness of such experimental tests. Our results show the vaccine could provide a powerful tool for mitigation and emphasises the need for studies considering ethical and practical issues of vaccination for wildlife conservation.

ecology↗

Mass mortality events in the sub-Antarctic Indian Ocean caused by long-distance circumpolar spread of highly pathogenic avian influenza H5N1 clade 2.3.4.4b

Since 2020, the outbreak of highly pathogenic avian influenza (HPAI) virus clade 2.3.4.4b has turned into the largest documented panzootic to date, reaching the sub-Antarctic region and Antarctica via the tip of South America in 2023. Here, we describe its recent arrival into the Indian Ocean sub-Antarctic archipelagos of Crozet and Kerguelen, where we first detected the virus in October 2024 in dead southern elephant seals, king penguins, gentoo penguins, brown skuas and kelp gulls. While the panzootic is ongoing, it has already caused unprecedented and alarming mortalities of southern elephant seals. We collected brain swabs from various seal and bird carcasses, subsequently isolated the virus and obtained 25 novel HPAI H5N1 clade 2.3.4.4b sequences. Our phylogenetic and phylogeographic analyses show that there have been independent introductions of the virus to Crozet and Kerguelen, from the distant South Georgia Islands in the Southern Atlantic, and not from the more nearby coasts of South Africa. Our results point to a year-long gap in genomic surveillance in the south polar region, obscuring how HPAI H5N1 clade 2.3.4.4b is spreading in the sub-Antarctic and illustrating the difficulties in tracking pathogen dispersal in the region. Locally, our phylogenetic analyses show that the virus is transmitted between different species. Moreover, our serological analyses show that some southern elephant seal pups had mounted an anti-H5 antibody response. With the spread to Crozet and Kerguelen, HPAI H5N1 2.3.4.4b is moving ever closer to Australia and New Zealand, which currently remain free from infections with this strain, and represents a major threat to the sub-Antarctic wildlife. Our results provide key elements to enable stakeholders to anticipate the arrival and spread of the virus in remote areas of critical wildlife conservation concerns.

microbiology↗

Chronic IFNα treatment induces leukopoiesis, increased plasma succinate and immune cell metabolic rewiring

Although clinically effective, the actions of IFN, either produced endogenously or by therapeutic delivery, remain poorly understood. Emblematic of this research gap is the disparate array of notable side effects that occur in susceptible individuals, such as neuropsychiatric consequences, autoimmune phenomena, and infectious complications. We hypothesised that these complications are driven at least in part by dysregulated cellular metabolism. Male Wistar rats were treated with either 170,000 IU/kg human recombinant IFN-2a or BSA/saline (0.9% NaCl) three times per week for three weeks. Bone marrow (BM) immune cells were isolated from the excised femurs for glycolytic rate and mitochondrial function assessment using Agilent Seahorse Technology. Frequencies of immune cell populations were assessed by flow cytometry to determine whether leukopoietic changes had occurred in both blood and BM. Plasma levels of lactate and succinate were also determined. BMDMs were metabolically assessed as above, as well as their metabolic response to an antigenic stimulus (iH37Rv). We observed that BM immune cells from IFN-treated rats exhibit a hypermetabolic state (increased basal OCR/GlycoPER) with decreased mitochondrial metabolic respiration and increased non-mitochondrial OCR. Flow cytometry results indicated an increase in immature granulocytes (RP1-SSChi CD45lo) and classical monocytes (CD43lo RP1hi) in the blood, together with increased succinate levels in the plasma. BMDMs from IFN-treated rats retained the hypermetabolic phenotype after differentiation and failed to induce a step-up in glycolysis and mitochondrial respiration after bacterial stimulation. This work provides the first evidence of the effects of IFN treatment in inducing hypermetabolic immune features that are associated with markers of inflammation, leukopoiesis, and defective responses to bacterial stimulation.

immunology↗