Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use

Genome-resolved metagenomics provides insights into the microbial-mediated sulfur and nitrogen cycling in temperate seagrass meadows

The presence of seagrasses facilitates numerous microbial-mediated biogeochemical cycles, with sulfur- and nitrogen-cycling microorganisms playing crucial roles as regulators. Despite efforts to comprehend the diversity of microbes in seagrass ecosystems, the metabolic functions of these benthic microorganisms in seagrass sediments remain largely unknown. Using metagenomics, we provide insights into the sulfur- and nitrogen-cycling pathways and key metabolic capacities of microorganisms in both Z. japonica-colonized and unvegetated sediments over a seasonal period. Taxonomic analysis of N and S cycling genes revealed that δ- and γ- proteobacteria dominated the benthic sulfate-reducing bacteria, while α- and γ-proteobacteria played a significant role in the sulfur-oxidation processes. The proteobacterial lineages were also major contributors to the benthic nitrogen cycling. However, at a finer taxonomic resolution, microbial participants in different processes were observed to be highly diverse and mainly driven by environmental factors such as temperature and salinity. The gene pools of sulfur and nitrogen cycles in the seagrass sediments were dominated by genes involved in sulfide oxidation (fccA) and hydroxylamine oxidation (hao), respectively. Seagrass colonization elevated the relative abundance of genes responsible for sulfite production (phsC), hydroxylamine oxidation (hao), and nitrogen fixation (nifK), but suppressed sulfur oxidation (soxXYZ) and denitrification (nosZ and nirS). The prevalence of proteobacterial lineages functioned with versatile capabilities in both sulfur and nitrogen cycles in seagrass ecosystems, highlighting tight couplings between these processes, which was further supported by the recovery of 83 metagenome-assembled genomes (MAGs). These findings broaden our understanding of the biogeochemical processes that are mediated by microorganisms in seagrass ecosystems

Generation and Comprehensive Analysis of Host Cell Interactome of the PA Protein of the Highly Pathogenic H5N1 Avian Influenza Virus in Mammalian Cells

Accumulating data have identified the important roles of PA protein in replication and pathogenicity of influenza A virus (IAV). Identification of host factors that interact with the PA protein may accelerate our understanding of IAV pathogenesis. In this study, using immunoprecipitation assay combined with liquid chromatography-tandem mass spectrometry, we identified 278 human cellular proteins that might interact with PA of H5N1 IAV. Gene Ontology annotation revealed that the identified proteins are highly associated with viral translation and replication. Further KEGG pathway analysis of the interactome profile highlighted cellular pathways associated with translation, infectious disease, and signal transduction. In addition, Diseases and Functions analysis suggested that these cellular proteins are highly related with Organismal Injury and Abnormalities and Cell Death and Survival. Moreover, two cellular proteins (nucleolin and eukaryotic translation elongation factor 1-alpha 1) identified both in this study and others were further validated to interact with PA using co-immunoprecipitation and co-localization assays. Therefore, this study presented the interactome data of H5N1 IAV PA protein in human cells which may provide novel cellular target proteins for elucidating the potential molecular functions of PA in regulating the lifecycle of IAV in human cells

Newcastle Disease Virus as a Vaccine Vector for 20 Years: A Focus on Maternally Derived Antibody Interference

It has been 20 years since Newcastle disease virus (NDV) was first used as a vector. The past two decades have witnessed remarkable progress in vaccine generation based on the NDV vector and optimization of the vector. Protective antigens of a variety of pathogens have been expressed in the NDV vector to generate novel vaccines for animals and humans, highlighting a great potential of NDV as a vaccine vector. More importantly, the research work also unveils a major problem restraining the NDV vector vaccines in poultry, i.e., the interference from maternally derived antibody (MDA). Although many efforts have been taken to overcome MDA interference, a lack of understanding of the mechanism of vaccination inhibition by MDA in poultry still hinders vaccine improvement. In this review, we outline the history of NDV as a vaccine vector by highlighting some milestones. The recent advances in the development of NDV-vectored vaccines or therapeutics for animals and humans are discussed. Particularly, we focus on the mechanisms and hypotheses of vaccination inhibition by MDA and the efforts to circumvent MDA interference with the NDV vector vaccines. Perspectives to fill the gap of understanding concerning the mechanism of MDA interference in poultry and to improve the NDV vector vaccines are also proposed

Discovering the Characteristics of Community Structures and Functional Properties of Epiphytic Bacteria on Spartina alterniflora in the Coastal Salt Marsh Area

The invasive submerged Spartina alterniflora is dominant in the coastal Yellow River Delta wetland. Although sediment microorganisms have been found to mediate the nutrient cycle in wetlands, the role of epiphytic bacteria on submerged S. alterniflora has rarely drawn attention. In the present study, we analyzed the characteristics of epiphytic microbial community diversity and functional properties related to S. alterniflora in summer and winter by Illumina MiSeq sequencing and functional prediction. Marked high abundances of Proteobacteria, Actinobacteriota, Planctomycetota, Cyanobacteria and Desulfobacterota were found in S. alterniflora epiphytic microbiome. Beta diversity based on NMDS and LDA analysis revealed that the distribution of these epiphytic microbial communities clustered according to the leaf locations and variation in seasons. Environmental factors, including temperature, salinity, DO and total organic matter, exert important roles in impacting the microbial community. Significantly higher abundances of chemoheterotrophy, aerobic_chemoheterotrophy, hydrocarbon degradation, fermentation, nitrate reduction and nitrate respiration were correlated with the submerged S. alterniflora epiphytic microbiome. Collectively, the results indicated that S. alterniflora epiphytic bacterial community diversity and functional guilds varied greatly with variations in leaf locations and seasons. These results will also provide guidance for the isolation of functional bacteria in controlling plant spread

Strong innate immune response and cell death in chicken splenocytes infected with genotype VIId Newcastle disease virus

Abstract Background Genotype VIId Newcastle disease virus (NDV) isolates induce more severe damage to lymphoid tissues, especially to the spleen, when compared to virulent viruses of other genotypes. However, the biological basis of the unusual pathological changes remains largely unknown. Methods Virus replication, cytokine gene expression profile and cell death response in chicken splenocytes infected with two genotype VIId NDV strains (JS5/05 and JS3/05), genotype IX NDV strain F48E8 and genotype IV NDV strain Herts/33 were evaluated. Statistical significance of differences between experimental groups was determined using the Independent-Samples T test. Results JS5/05 and JS3/05 caused hyperinduction of type I interferons (IFNs) (IFN-α and -β) during detection period compared to F48E8 and Herts/33. JS5/05 increased expression level of IFN-γ gene at 6 h post-inoculation (pi) and JS3/05 initiated sustained activation of IFN-γ within 24 h pi, whereas transcriptional levels of IFN-γ remained unchanged at any of the time points during infection of F48E8 and Herts/33. In addition, compared to F48E8 and Herts/33, JS3/05 and JS5/05 significantly increased the amount of free nucleosomal DNA in splenocytes at 6 and 24 h pi respectively. Annexin-V and Proidium iodid (PI) double staining of infected cells showed that cell death induced by JS3/05 and JS5/05 was characterized by marked necrosis compared to F48E8 and Herts/33 at 24 h pi. These results indicate that genotype VIId NDV strains JS3/05 and JS5/05 elicited stronger innate immune and cell death responses in chicken splenocytes than F48E8 and Herts/33. JS5/05 replicated at a significantly higher efficiency in splenocytes than F48E8 and Herts/33. Early excessive cell death induced by JS3/05 infection partially impaired virus replication. Conclusions Viral dysregulaiton of host response may be relevant to the severe pathological manifestation in the spleen following genotype VIId NDV infection.</p

Seasonal Dynamics of Bathyarchaeota-Dominated Benthic Archaeal Communities Associated with Seagrass (Zostera japonica) Meadows

Little is known about the seasonal dynamic of archaeal communities and their potential ecological functions in temperate seagrass ecosystems. In this study, seasonal changes in diversity, community structure, and potential metabolic functions of benthic archaea in surface sediments of two seagrass meadows along the northern Bohai Sea in China were investigated using Miseq sequencing of the 16S rRNA gene and Tax4Fun2 functional prediction. Overall, Crenarchaeota (mainly Bathy-15, Bathy-8, and Bathy-6) dominated, followed by Thermoplasmatota, Asgardarchaeota, and Halobacterota, in terms of alpha diversities and relative abundance. Significant seasonal changes in the entire archaeal community structure were observed. The major phyla Methanobacteria, Nitrosopumilales, and genus Methanolobus had higher proportions in spring, while MBG-D and Bathyarchaeota were more abundant in summer and autumn, respectively. Alpha diversities (Shannon and Simpson) were the highest in summer and the lowest in autumn (ANOVA test, p < 0.05). Salinity, total organic carbon, and total organic nitrogen were the most significant factors influencing the entire archaeal community. Higher cellulose and hemicellulose degradation potentials occurred in summer, while methane metabolism potentials were higher in winter. This study indicated that season had strong effects in modulating benthic archaeal diversity and functional potentials in the temperate seagrass ecosystems

Seagrass vegetation affect the vertical organization of microbial communities in sediment

Seagrasses represent high primary productivity and provide important ecosystem services to the marine environment. Seagrass-associated microbial communities are playing essential ecological functional roles in biogeochemical cycles. However, little is known about the effect of seagrass vegetation on microbial communities in sediment. In the present study, the sediment cores of seagrass bed (dominated by Zostera japonica and Zostera marine) and degradation area in Swan Lake (China) were sampled; then, biogeochemical parameters were analyzed, and microbial community composition was investigated by using high-throughput sequencing of the 16S rRNA gene. The results showed that the presence of seagrass could lead to a decrease in the richness and diversity of the microbial community. In the vertical direction, a pronounced shift from Proteobacteria-dominated upper layers to Chloroflexi and Crenarchaeota-dominated deep layers in all sediment cores were observed. Besides, Bathyarchaeia is more abundant at degradation area, while Vibrionaceae, Sulfurovum and Lokiarchaeial overrepresent at the seagrass bed area. Vibrionaceae was abundant in the rhizosphere of Z. marina and Z. japonica, and the proportions reached 84.45% and 63.89%, respectively. This enrichment of Vibrio spp. may be caused by the macrobenthic species near the seagrass rhizosphere, and these Vibrio spp. reduced the diversity and stability of microbial community, which may lead to the degradation of seagrass. This study would provide clues for the distribution patterns and niche preferences of seagrass microbiome. The conservation strategy of seagrass would be further elucidated from the perspective of the microbiome