Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 mg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 mg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60 % in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination agains

Man-algorithm Cooperation Intelligent Design of Clothing Products in Multi Links

The changes in technology have led to a synchronous change in the clothing design method, as well as media and artistic aesthetics in the same period. The intelligence algorithm is constantly increasing its participation in development and production in the clothing industry. In this study, a variety of intelligent algorithms, including the parameterised numer state algorithm, Generative Adversarial Networks, and style transfer were introduced into the multi-links of clothing product design and development, such as clothing shape, print pattern, texture craft, product vision, and so on. Then, an innovative clothing design method based on the cooperation of the intelligent algorithm and various human functional roles was constructed. The method improves the efficiency of the multiple links of clothing design, such as generating 10000 printing patterns every 72.12 seconds, and completing the migration of 92.7 frames of the garment process style every second. To a certain extent, this study realizes the scale economy of clothing design and reduces its marginal cost through the unlimited computing power brought about by Moore’s law of digital technology, which provides a reference for the exploration of clothing design in the era of industry 4.0

Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge.

The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates

Integrated gut virome and bacteriome dynamics in COVID-19 patients

SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes

Production of the H7N9/PR8 influenza vaccine candidate using reverse genetics, and the size distribution and shapes of the virus particles.

<p>(A) Preparation of the H7N9 vaccine seed strain using eight-plasmid reverse genetics. (B) Electron micrograph of recombinant H7N9/PR8 virus particles. (C) Most (73%) of 200 H7N9/PR8 virus particles were 80–120 nm in diameter.</p

Antibody responses to the H7N9/PR8 split vaccine in mice.

<p>Groups of 20 BALB/c mice were immunized intramuscularly at weeks 0 and 2 with 7.5, 15, 30, or 45 µg (HA levels) of the H7N9/PR8 split vaccine. (A) HI antibody responses to the (wt) AnHui virus after vaccination as described above. Serum samples were collected on day 0; 2 weeks after priming; and 2, 4, and 8 weeks after boosting. (B) Serum IgG titers against the (wt) AnHui virus measured 2 weeks after both the first and second doses of vaccine. (C) The ratios of serum IgG1 to IgG2a titers against the (wt) AnHui virus, calculated 2 weeks after the second dose of vaccine. The data are presented as means ± SDs of the data from three experiments, each performed in duplicate. HI, hemagglutination inhibition; PBS, phosphate-buffered saline. 2WPD1: 2 weeks post-vaccination with dose 1. 2WPD2: 2 weeks post-vaccination with dose 2; 4WPD2: 4 weeks post-vaccination with dose 2; 8WPD2: 8 weeks post-vaccination with dose 2.</p

Live attenuated monovalent influenza A (H7N9) vaccines induce antibody responses in mice.

<p>Groups of mice were i.n. immunized at weeks 0 and 2 with various doses of 10⁴ CCID₅₀, 10⁵ CCID₅₀, and 10⁶ CCID₅₀ of the Ah01/AA ca vaccine or mock-infected with PBS. Levels of HI (A) and NT (B) antibodies against wt Influenza H7N9 virus in sera 2 weeks after prime and boost. Error bars indicate SDs (n = 8).</p