Dietary vitamin A restriction increases marbling in feedlot cattle; however, its effect on antibody responses to vaccines is unknown. A low vitamin A diet compromised the serum IgG1 responses against inactivated BCoV vaccine, which suggested suppressed T-helper 2-associated antibody (IgG1) responses. Thus, low vitamin A diets may compromise the effectiveness of viral vaccines and render calves more susceptible to infectious disease.

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Parenteral administration of killed/inactivated swine influenza A virus (SwIAV) vaccine in weaned piglets provides variable levels of immunity due to the presence of preexisting virus specific maternal derived antibodies (MDA). To overcome the effect of MDA on SwIAV vaccine in piglets, we developed an intranasal deliverable killed SwIAV antigen (KAg) encapsulated chitosan nanoparticles called chitosan-based NPs encapsulating KAg (CS NPs-KAg) vaccine. Further, to target the candidate vaccine to dendritic cells and macrophages which express mannose receptor, we conjugated mannose to chitosan (mCS) and formulated KAg encapsulated mCS nanoparticles called mannosylated chitosan-based NPs encapsulating KAg (mCS NPs-KAg) vaccine. In MDA-positive piglets, prime-boost intranasal inoculation of mCS NPs-KAg vaccine elicited enhanced homologous (H1N2-OH10), heterologous (H1N1-OH7), and heterosubtypic (H3N2-OH4) influenza virus-specific secretory IgA (sIgA) antibody response in nasal passage compared to CS NPs-KAg vaccinates. In vaccinated upon challenged with a heterologous SwIAV H1N1, both mCS NPs-KAg and CS NPs-KAg vaccinates augmented H1N2-OH10, H1N1-OH7, and H3N2-OH4 virus-specific sIgA antibody responses in nasal swab, lung lysate, and bronchoalveolar lavage (BAL) fluid; and IgG antibody levels in lung lysate and BAL fluid samples. Whereas, the multivalent commercial inactivated SwIAV vaccine delivered intramuscularly increased serum IgG antibody response. In mCS NPs-KAg and CS NPs-KAg vaccinates increased H1N2-OH10 but not H1N1-OH7 and H3N2-OH4-specific serum hemagglutination inhibition titers were observed. Additionally, mCS NPs-KAg vaccine increased specific recall lymphocyte proliferation and cytokines IL-4, IL-10, and IFNγ gene expression compared to CS NPs-KAg and commercial SwIAV vaccinates in tracheobronchial lymph nodes. Consistent with the immune response both mCS NPs-KAg and CS NPs-KAg vaccinates cleared the challenge H1N1-OH7 virus load in upper and lower respiratory tract more efficiently when compared to commercial vaccine. The virus clearance was associated with reduced gross lung lesions. Overall, mCS NP-KAg vaccine intranasal immunization in MDA-positive pigs induced a robust cross-reactive immunity and offered protection against influenza virus.

We report on analysis of englacial radio-frequency (RF) pulser data received over horizontal baselines of 1–5 km, based on broadcasts from two sets of transmitters deployed to depths of up to 1500 meters at the South Pole. First, we analyze data collected using two RF bicone transmitters 1400 meters below the ice surface, and frozen into boreholes drilled for the IceCube experiment in 2011. Additionally, in Dec., 2018, a fat-dipole antenna, fed by one of three high-voltage (𝒪(1 kV)), fast (𝒪(1-5 ns risetime)) signal generators was lowered into the 1700-m deep icehole drilled for the South Pole Ice Core Experiment (SPICE), approximately 3 km from the geographic South Pole. Signals from transmitters were recorded on the five englacial multi-receiver ARA stations, with receiver depths between 60–200 m. From analysis of deep transmitter data, we estimate: i) the range of refractive index profiles of Antarctic ice with depth allowed by our measurements, ii) due to birefringence, a time difference between arrival times for vertically polarized vs. horizontally polarized signals (per km) for horizontally propagating signal, and iii) for the first time, the attenuation length for electromagnetic signals in the radio-frequency regime broadcast horizontally (rather than reflected vertically from bedrock). We additionally present data suggesting anomalous ice propagation effects, and contrary to expectations for a transport medium with a smoothly varying refractive index profile. Our results imply negligible uncertainty in overall neutrino detection volume due to refractive index uncertainties. Our birefringence time-difference measurements are fit to the functional form δt(H−V) [ns/km]=acosθ+b, with H/V the signal arrival times for the horizontally/vertically polarized EM signal components, and θ the opening angle in the horizontal plane between the signal propagation direction and the local ice flow direction, extracting a=8.3±1.3 ns/km, and b=-8.6±0.9 ns/km (errors combined statistical and systematic), allowing a ∼15% range estimate for future measurements of in-ice neutrino interactions. Finally, we find attenuation length values clustering around 1.5 km, with measurements from the bicone transmitters yielding Latten=1.43±0.25±0.37 km. Taken together, these measurements support cold polar ice as a near-optimal platform for ultra-high energy neutrino detectors.

Live attenuated vaccines (LAVs) replicate in the respiratory/oral mucosa, mimic natural infection, and can induce mucosal and systemic immune responses to the full repertoire of SARS-CoV-2 structural/nonstructural proteins. Generally, LAVs produce broader and more durable protection than current COVID-19 vaccines. We generated a temperature-sensitive (TS) SARS-CoV-2 mutant TS11 via cold-adaptation of the WA1 strain in Vero E6 cells. TS11 replicated at >4 Log10-higher titers at 32 °C than at 39 °C. TS11 has multiple mutations, including those in nsp3, a 12-amino acid-deletion spanning the furin cleavage site of the S protein and a 371-nucleotide-deletion spanning the ORF7b-ORF8 genes. We tested the pathogenicity and protective efficacy of TS11 against challenge with a heterologous virulent SARS-CoV-2 D614G strain 14B in Syrian hamsters. Hamsters were randomly assigned to mock immunization-challenge (Mock-C) and TS11 immunization-challenge (TS11-C) groups. Like the mock group, TS11-vaccinated hamsters did not show any clinical signs and continuously gained body weight. TS11 replicated well in the nasal cavity but poorly in the lungs and caused only mild lesions in the lungs. After challenge, hamsters in the Mock-C group lost weight. In contrast, the animals in the TS11-C group continued gaining weight. The virus titers in the nasal turbinates and lungs of the TS11-C group were significantly lower than those in the Mock-C group, confirming the protective effects of TS11 immunization of hamsters. Histopathological examination demonstrated that animals in the Mock-C group had severe pulmonary lesions and large amounts of viral antigens in the lungs post-challenge; however, the TS11-C group had minimal pathological changes and few viral antigen-positive cells. In summary, the TS11 mutant was attenuated and induced protection against disease after a heterologous SARS-CoV-2 challenge in Syrian hamsters.