During autumn/winter in 2016 – 2017 and 2020 – 2021, highly pathogenic avian influenza viruses (HPAIV) caused severe outbreaks in Germany and Europe. Multiple clade 2.3.4.4b H5 HPAI subtypes were responsible for increased mortality in wild birds and high mortality and massive losses in the poultry sector. To clarify putative entry sources and delineate interconnections between outbreaks in poultry holdings and wild birds, we applied whole-genome sequencing and phylodynamic analyses combined with the results of epidemiological outbreak investigations. Varying outbreak dynamics of the distinct reassortants allowed for the identification of individual, putatively wild bird-mediated entries into backyard holdings, several clusters comprising poultry holdings, local virus circulation for several weeks, direct farm-to-farm transmission and potential reassortment within a turkey holding with subsequent spill-over of the novel reassorted virus into the wild bird population. Whole-genome sequencing allowed for allowed for a unique high-resolution molecular epidemiology analysis of HPAIV H5Nx outbreaks, recommended to be used as a standard tool. The presented detailed account of the genetic, temporal and geographical characteristics of the recent German HPAI H5Nx situation emphasizes the role of poultry holdings as an important source of novel genetic variants and reassortants.
In November 2016, an influenza A(H5N8) outbreak caused deaths of wild birds and domestic poultry in Germany.Clade 2.3.4.4 virus was closely related to viruses detected at the Russia-Mongolia border in 2016 but had new polymerase acidic and nucleoprotein segments.These new strains may be more efficiently transmitted to and shed by birds.D uring 2014-2015, after massive outbreaks of highly pathogenic avian influenza (HPAI) on the Korean Peninsula, subtype H5N8 viruses (group A clade 2.3.4.4) caused outbreaks among wild birds and domestic poultry in central Asia, Russia, and central Europe (1,2).Strains of this clade, and novel reassortants thereof, were transferred to North America (3).Transcontinental spread of these strains and an earlier HPAI virus (HPAIV) of the goose/Guangdong lineage of subtype H5N1 has been linked to dissemination by migratory wild birds (4).We describe a novel reassortant of HPAIV A(H5N8) within group B clade 2.3.4.4,which causes lethal infections in hundreds of wild birds and domestic poultry in Germany and elsewhere in Europe. The StudyIn late May 2016, a group B clade 2.3.4.4 H5N8 virus was detected in dead and hunted wild birds at Lake Uvs-Nuur, at the Russia-Mongolia border (5).On November 7, 2016, many dead tufted ducks (Aythya fuligula) were found at Lake Plön in Schleswig-Holstein, northern Germany, and at Lake Constance in Baden-Württemberg, southern Germany (Figure 1); most were positive for H5N8.The epidemic among wild birds continued and spread toward the center of the country (Figure 1).As of December 2016, several backyard holdings, 4 zoos, and a few large commercial Outbreaks among Wild Birds and DomesticPoultry Caused by Reassorted Influenza A(H5N8) Clade 2.3.4.4 Viruses, Germany, 2016
Abstract Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve control of the COVID-19 pandemic. We compare monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein in a transgenic mouse and a Wistar rat model. The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8 + T cells, antigen-specific CD4 + and CD8 + responses, and protects transgenic female mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.
