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Simple Summary: Left displaced abomasum is a common disease among Holstein cattle that is causing significant economic losses. The exact causes of the disease are unknown, but it is assumed that LDA is multifactorial in nature. Predisposition to the displacement has been shown to be inherited. We conducted a genome-wide study to identify statistical associations between certain mutations and left displaced abomasum in Holstein cows from several farms in the Leningrad region. We found suggestive statistical associations with this disease and several mutations located in a set of genes involved in a variety of physiological processes. Some of these processes may be directly related to the development of the disease being studied. In addition, we conducted runs of homozygosity analysis and found that cows with displaced abomasum are more likely than healthy cows to carry a specific state of genomic regions containing genes associated with body shape, including width. This may indicate the role of this trait in the development of the disease. Left displaced abomasum (LDA) is a multifactorial disease of cattle that occurs mainly during the transition postpartum period and is characterized by a decrease in milk production and an increased risk of culling. Several studies have been conducted confirming the hereditary nature of predisposition to this disease. The aim of our study is to identify genetic associations characterizing the genomic variability of susceptibility to LDA in Holstein cattle of the Leningrad region of the Russian Federation. The objects of this study were 360 highly productive dairy cows divided into two groups: animals with LDA, and healthy ones (control). Runs of homozygosity analysis revealed one ROH on BTA13 that was found to be significantly more prevalent in the group of animals with LDA than in the healthy group. Fourteen candidate SNPs were found to be nominally associated with left displacement of the abomasum (p-value < 1 × 10−4). When performing functional annotation of genes containing associated polymorphisms or located close to them, candidate genes presumably associated with the development of LDA were identified: ABCB11, SRP72, RGS18, SOX4, GSG1L, FBXL19, and PNPLA4. [ABSTRACT FROM AUTHOR]

Zoo conditions are unique for reindeer, since domestic reindeer are not kept in captive facilities like cattle. In the zoo, reindeer are usually surrounded by many different animals that they would never encounter naturally. Thus, they might be infected with new helminths. Numerous petting zoos raise concerns about the safety of tactile interactions for human visitors. Our study is the first large-scale one. Qualitative and quantitative fecal analyses were carried out for 233 reindeer distributed over 50 Russian zoos according to the National Standard of the Russian Federation (GOST R 54627-2011) Ruminant animals—Methods of Laboratory Helminthological Diagnostics. Where possible, DNA analyses of helminths were performed targeting internal transcribed spacer region. As a result, F. hepatica, Paramphistomum sp., Moniezia sp. (including M. expansa), gastrointestinal strongylids (including Nematodirus spp.), Dictyocaulus sp., E. rangiferi, Trichuris sp., and Capillaria sp. were found in 106 (45%) zoo reindeer. All these helminths were previously reported in reindeer and pose no direct danger for humans. The intensity of invasions was mostly low. Fecal examination might be considered as an indirect method for mange diagnostics, as Chorioptes and Demodex mites were found in reindeer fecal samples. The latter may represent a novel species of mite specific for reindeer. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20–40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA. [ABSTRACT FROM AUTHOR]

Mesozoic gabbro from the Stanovoy convergent margin and adakitic dacite lava from the Pliocene–Quaternary Bakening volcano in Kamchatka contain iron–titanium oxide–apatite–sulfide–sulfate (ITOASS) microinclusions along with abundant isolated iron–titanium minerals, sulfides and halides of base and precious metals. Iron–titanium minerals include magnetite, ilmenite and rutile; sulfides include chalcopyrite, pyrite and pyrrhotite; sulfates are represented by barite; and halides are predominantly composed of copper and silver chlorides. Apatite in both gabbro and adakitic dacite frequently contains elevated chlorine concentrations (up to 1.7 wt.%). Mineral thermobarometry suggests that the ITOASS microinclusions and associated Fe-Ti minerals and sulfides crystallized from subduction-related metal-rich melts in mid-crustal magmatic conduits at depths of 10 to 20 km below the surface under almost neutral redox conditions (from the unit below to the unit above the QFM buffer). The ITOASS microinclusions in gabbro and adakite from the Russian Far East provide possible magmatic links to iron oxide–apatite (IOA) and iron oxide–copper–gold (IOCG) deposits and offer valuable insights into the early magmatic (pre-metasomatic) evolution of the IOA and ICOG mineralized systems in paleo-subduction- and collision-related geodynamic environments. [ABSTRACT FROM AUTHOR]

Background: Influenza viruses continue to cause a significant social and economic burden globally. Vaccination is recognized as the most effective measure to control influenza. Live attenuated influenza vaccines (LAIVs) are an effective means of preventing influenza, especially among children. A reverse genetics (RG) system is required to rapidly update the antigenic composition of vaccines, as well as to design LAIVs with a broader spectrum of protection. Such a system has been developed for the Russian LAIVs only for type A strains, but not for influenza B viruses (IBV). Methods: All genes of the B/USSR/60/69 master donor virus (B60) were cloned into RG plasmids, and the engineered B60, as well as a panel of IBV LAIV reassortants were rescued from plasmid DNAs encoding all viral genes. The engineered viruses were evaluated in vitro and in a mouse model. Results: The B60 RG system was successfully developed, which made it possible to rescue LAIV reassortants with the desired antigenic composition, including hybrid strains with hemagglutinin and neuraminidase genes belonging to the viruses from different IBV lineages. The LAIV candidate carrying the HA of the B/Victoria-lineage virus and NA from the B/Yamagata-lineage virus demonstrated optimal characteristics in terms of safety, immunogenicity and cross-protection, prompting its further assessment as a broadly protective component of trivalent LAIV. Conclusions: The new RG system for B60 MDV allowed the rapid generation of type B LAIV reassortants with desired genome compositions. The generation of hybrid LAIV reassortants with HA and NA genes belonging to the opposite IBV lineages is a promising approach for the development of IBV vaccines with broad cross-protection. [ABSTRACT FROM AUTHOR]

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain that has naturally high pathogenic properties in mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. In addition, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity in mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. In contrast, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed. [ABSTRACT FROM AUTHOR]

Iron and iron–manganese deposits form three closely spaced clusters within the Lesser Khingan Range of the Russian Far East. Fe-Mn mineralization is hosted in Vendian–Cambrian carbonates and composed of magnetite, hematite, braunite, haussmanite, rhodochrosite and pyrolusite. The iron–manganese ores are closely associated with explosive intermediate–felsic breccias, magnetite-rich lavas, dolerites and mineralized lithocrystalloclastic tuffs. Magmatic rocks display both concordant and discordant relationships with Fe-Mn mineralization and contain abundant xenoliths of host carbonates. Both magmatic rocks (with the exception of Nb-enriched dolerites) and Fe-Mn ores are characterized by variable enrichments in large-ion lithophile and light rare earth elements and strong depletions in high-field strength elements compatible with the broad subduction setting for explosive volcanism and associated hydrothermal Fe-Mn ore mineralization. Nd-Sr isotope systematics suggest contamination by both ancient and juvenile continental crust and the involvement of recycled pelagic sediment in the formation of Fe-Mn deposits in the Lesser Khingan Range of the Russian Far East. [ABSTRACT FROM AUTHOR]

The Ildeus mafic–ultramafic complex represents plutonic roots of a Triassic magmatic arc tectonically emplaced into the thickened uppermost crust beneath the Mesozoic Stanovoy collided margin. The mafic–ultramafic complex cumulates host Ni-Co-Cu-Pt-Ag-Au sulfide-native metal-alloy mineralization produced through magmatic differentiation of subduction-related primary mafic melt. This melt was sourced in the metal-rich sub-arc mantle wedge hybridized by reduced high-temperature H-S-Cl fluids and slab/sediment-derived siliceous melts carrying significant amounts of Pt, W, Au, Ag, Cu and Zn. Plutonic rocks experienced a pervasive later-stage metasomatic upgrade of the primary sulfide–native metal–alloy assemblage in the presence of oxidized hydrothermal fluid enriched in sulfate and chlorine. The new metasomatic assemblage formed in a shallow epithermal environment in the collided crust includes native gold, Ag-Au, Cu-Ag and Cu-Ag-Au alloys, heazlewoodite, digenite, chalcocite, cassiterite, galena, sphalerite, acanthite, composite Cu-Zn-Pb-Fe sulfides, Sb-As-Se sulfosalts and Pb-Ag tellurides. A two-stage model for magmatic–hydrothermal transport of some siderophile (W, Pt, Au) and chalcophile (Cu, Zn, Ag) metals in subduction–collision environments is proposed. [ABSTRACT FROM AUTHOR]

Igneous rocks from the Russian Far East contain Cu-Ag-Au microspherules with distinct exterior and interior structures, compositions and assemblages of Cu-rich micro-inclusions. Natural microspherules are compared in this study with technogenic Cu-Ag-Au microspherules, which are experimentally produced and extracted from gold scrap jewelry. The following set of diagnostic criteria are considered to distinguish natural from technogenic microspherules on a genetic basis as follows: (1) compacted-related features versus cellular appearance of the exterior; (2) lack of exsolution- or crystallization-related features in natural and domain-type internal structure in technogenic microspherules; (3) absence of spherical copper-oxide inclusions along with meniscus-type textural boundaries in technogenic mcirospherules; (4) pure copper-oxide composition of inclusions versus the common presence of Fe, Ni, Zn, Cu and Na in natural microspherules. The diagnostic characteristics of natural Cu-Ag-Au microspherules suggest extremely fast cooling rates during their formation, which is possible during violent explosive volcanic eruptions or injection of partially molten, pulverized metal alloys into shallow intra-crustal cavities and fault-related tectonic gashes. [ABSTRACT FROM AUTHOR]

The Paleozoic volcano-sedimentary rocks within the structural basement of the horst-and-graben system of the Catalan Coastal Ranges (CCR) are composed of black shale, volcaniclastic sediments, lava flows, sills and lithocrystalloclastic tuffs. Paleozoic sediments are depleted in high-field strength elements (HFSE) such as Nb, Ta, Zr, Hf and Ti, suggesting their accumulation within the Andean-type active continental margin environment. Volcanic rocks within the Paleozoic CCR sequence belong to shoshonitic and high-K volcanic series and are enriched in Cs, Rb and Ba and depleted in HFSE, which is consistent with their derivation from metasomatized (possibly through deep recycling of pelagic sediments) subduction-related mantle source. The presence of sills (sill-sediment complex) suggests that Paleozoic basement of the CCR was formed within the rifted active continental margin or an arc-back-arc basin system akin to the modern Western Pacific subduction configuration. This complex volcanic terroir hosts world-class wines of the Priorat DOQ region. The presence of framboidal pyrite and magnetite, siderite, sphalerite xenotime, (La–Ce–Nd)-monazite, zircon and baddeleyite, as well as cuprite, tenorite and cupriferous and native silver in volcanic-derived black shale (and consequently in the world-famous "llicorella" soil overlying it) may have had dramatic effects on wine quality and sensory characteristics. These mineral features, together with strong enrichment of Priorat shale in Au, Ag and, to a lesser extent, Pt could have pronounced effects on (1) rates and specific types of chemical reactions; (2) plant metabolism; (3) response to nutrient components and (4) determination of grape flavor. Volcanic wine terroirs, such as the Priorat DOQ region, are special geologic environments for wine growth, capable of producing unique wine aromatic and gustatory characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Artificial insemination is actively used in animal husbandry. It is important to know the quality of the sperm for artificial insemination. One of the indicators of sperm quality can be an assessment of energy metabolism, since energy is needed for sperm to move and fertilize the egg. We studied the respiration rate in spermatozoa of different animal species: bulls, stallions, boars, reindeer and roosters. To determine the production of energy (ATP), the substance 2.4-dinetrophenol (2.4-DNP) was used, which stopped the production of ATP. Semen was assessed before and after freezing. The evaluation showed the same response to the addition of 2.4-DNP to the semen of different species, as well as a sufficient relationship between the reaction of semen respiration to the addition of 2.4-DNP and the fertilizing ability of sperm. At the same time, no relationship was found between the respiratory rate and fertility. The 2.4-DNP test can be a suitable additional measure of sperm quality. To assess sperm quality, it is important to evaluate energy metabolism. The test substance 2.4-dinitrophenol (2.4-DNP) is an agent for destroying oxidative phosphorylation. 2.4-DNP shuts off the production of adenosine triphosphate (ATP) from oxidation and then, the respiration rate increases. If the respiratory chain is damaged, there is little or no response to adding 2.4-DNP. The aim of this study was to analyze the respiratory activity and oxidative phosphorylation in semen before and after freezing and compare the obtained data with the fertilizing ability of sperm. There was a reduction in sperm respiration rates in all species after thawing. The respiration of spermatozoa of boars, bulls, stallions, reindeers and chicken showed responses to 2.4-dinitrophenol. The only difference is in the strength of the response to the test substance. After freezing and thawing, respiratory stimulation by 2.4-DNP decreased. The results of our study show that respiration rate is not correlated with pregnancy rates and egg fertility. However, there was a high correlation between the stimulation of respiration by 2.4-dinitrophenol and pregnancy rates. The test for an increase in respiration rate after adding 2.4-dinitrophenol could be a suitable test of the fertilizing ability of sperm. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP366 influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Simple Summary: It is important to know the semen quality of sires as quickly as possible. The development of DNA testing methods led to their active introduction into the practice of breeding farm animals. Many studies show that variants of single nucleotide polymorphism loci can be effectively used in as genetic markers in breeding. The aim of our study was to look for the association of polymorphism genes with fresh sperm quality in Russian Holstein bulls. In this pilot study we found that some genotypes of the follicle-stimulating hormone receptor gene are associated with doublet volume, concentration, and the total number of spermatozoa and some genotypes of hormone inhibin gene with higher sperm concentration and volume of ejaculate. Polymorphisms in hormone receptor genes may be good markers of spermatogenesis. This will allow for the finding of bulls with poor sperm quality at an early age. The aim of the study was to search for new mutations in the previously studied gene loci of follicle-stimulating hormone receptor (FSHR), inhibin α (INHA), inhibin β A (INHAB), prolactin (PRL), transition protein 2 (TNP2), and sperm flagella 2 (SPEF2) by sequencing, as well as the search for associations of previously identified mutations at these loci with fresh semen quality in Russian Holstein bulls. Phenotypic data from 189 bulls was collected. Data was analyzed for most bulls for three years of semen collection. The maximum value of each semen quality indicator (doublet ejaculate volume, sperm concentration, progressive motility and total number of spermatozoa) were selected. SNPs were identified in the FSHR, INHA, INHAB, TNP2, SPEF2 genes. The PRL gene did not have polymorphism. Significant (p < 0.05) associations of polymorphisms in the FSHR gene with double ejaculate volume, concentration and total number of spermatozoa were identified. Polymorphism in the INHA gene was significantly associated (p < 0.05) with sperm concentration. Polymorphism in the INHAB gene was significantly associated (p < 0.05) with doublet ejaculate volume and total number of spermatozoa. Polymorphisms in the TNP2 and SPEF2 genes did not have significant associations with semen quality. The SNPs studied in our pilot work may be considered as candidate genetic markers in the selection of bulls. [ABSTRACT FROM AUTHOR]

Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required. [ABSTRACT FROM AUTHOR]

Simple Summary: The cryopreservation and long-term storage of semen is one of the methods for accelerated improvement of the genetic qualities of animals. However, horse breeders prefer to use fresh or chilled semen, as the fertilizing capacity of frozen equine semen is much lower. It is important to find extenders, or a combination of extenders, that will improve semen survival after freezing. It is also important that the extender can be easily and simply prepared for use. Steridyl is a concentrate to which you just need to add sterilized water. This extender was developed for ruminants. In this study we tested Steridyl for freezing stallion semen. The motility, morphology, energy metabolism, DNA damage, and fertility of sperm frozen in Steridyl were evaluated. As a result, Steridyl was shown to be a good extender for equine semen freezing. The fertilizing ability of stallion sperm after freezing is lower than in other species. The search for the optimal extender, combination of extenders, and the freezing protocol is relevant. The aim of this study was to compare lactose-chelate-citrate-yolk (LCCY) extender, usually used in Russia, and Steridyl® (Minitube) for freezing sperm of stallions. Steridyl is a concentrated extender medium for freezing ruminant semen. It already contains sterilized egg yolk. Semen was collected from nine stallions, aged from 7 to 12 years old. The total and progressive motility of sperm frozen in Steridyl was significantly higher than in semen frozen in LCCY. The number of spermatozoa with normal morphology in samples frozen in LCCY was 60.4 ± 1.72%, and with Steridyl, 72.4 ± 2.10% (p < 0.01). Semen frozen in Steridyl showed good stimulation of respiration by 2.4-DNP, which indicates that oxidative phosphorylation was retained after freezing–thawing. No differences among the extenders were seen with the DNA integrity of spermatozoa. Six out of ten (60%) mares were pregnant after artificial insemination (AI) by LCCY frozen semen, and 9/12 (75%) by Steridyl frozen semen. No differences among extenders were seen in pregnancy rate. In conclusion, Steridyl was proven to be a good diluent for freezing stallion semen, even though it was developed for ruminants. [ABSTRACT FROM AUTHOR]

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted. [ABSTRACT FROM AUTHOR]

The development of universal influenza vaccines has been a priority for more than 20 years. We conducted a preclinical study in ferrets of two sets of live attenuated influenza vaccines (LAIVs) expressing chimeric hemagglutinin (cHA). These vaccines contained the HA stalk domain from H1N1pdm09 virus but had antigenically unrelated globular head domains from avian influenza viruses H5N1, H8N4 and H9N2. The viral nucleoproteins (NPs) in the two sets of universal LAIV candidates were from different sources: one LAIV set contained NP from A/Leningrad/17 master donor virus (MDV), while in the other set this gene was from wild-type (WT) H1N1pdm09 virus, in order to better match the CD8 T-cell epitopes of currently circulating influenza A viruses. To avoid any difference in protective effect of the various anti-neuraminidase (NA) antibodies, all LAIVs were engineered to contain the NA gene of Len/17 MDV. Naïve ferrets were sequentially immunized with three doses of (i) classical LAIVs containing non-chimeric HA and NP from MDV (LAIVs (NP-MDV)); (ii) cHA-based LAIVs containing NP from MDV (cHA LAIVs (NP-MDV)); and (iii) cHA-based LAIVs containing NP from H1N1pdm09 virus (cHA LAIVs (NP-WT)). All vaccination regimens were safe, producing no significant increase in body temperature or weight loss, in comparison with the placebo group. The two groups of cHA-based vaccines induced a broadly reactive HA stalk-directed antibody, while classical LAIVs did not. A high-dose challenge with H1N1pdm09 virus induced significant pathology in the control, non-immunized ferrets, including high virus titers in respiratory tissues, clinical signs of disease and histopathological changes in nasal turbinates and lung tissues. All three vaccination regimens protected animals from clinical manifestations of disease: immunized ferrets did not lose weight or show clinical symptoms, and their fever was significantly lower than in the control group. Further analysis of virological and pathological data revealed the following hierarchy in the cross-protective efficacy of the vaccines: cHA LAIVs (NP-WT) > cHA LAIVs (NP-MDV) > LAIVs (NP-MDV). This ferret study showed that prototype universal cHA-based LAIVs are highly promising candidates for further clinical development. [ABSTRACT FROM AUTHOR]

Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virological and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused the majority of human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial. [ABSTRACT FROM AUTHOR]