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Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics. [ABSTRACT FROM AUTHOR]

Bluetongue (BT), a viral disease of ruminants, is endemic throughout South Africa, where outbreaks of different serotypes occur. The predominant serotypes can differ annually due to herd immunity provided by annual vaccinations using a live attenuated vaccine (LAV). This has led to both wild-type and vaccine strains co-circulating in the field, potentially leading to novel viral strains due to reassortment and recombination. Little is known about the molecular evolution of the virus in the field in South Africa. The purpose of this study was to investigate the genetic diversity of field strains of BTV in South Africa and to provide an initial assessment of the evolutionary processes shaping BTV genetic diversity in the field. Complete genomes of 35 field viruses belonging to 11 serotypes, collected from different regions of the country between 2011 and 2017, were sequenced. The sequences were phylogenetically analysed in relation to all the BTV sequences available from GenBank, including the LAVs and reference strains, resulting in the analyses and reassortment detection of 305 BTVs. Phylogenomic analysis indicated a geographical selection of the genome segments, irrespective of the serotype. Based on the initial assessment of the current genomic clades that circulate in South Africa, the selection for specific clades is prevalent in directing genome segment reassortment, which seems to exclude the vaccine strains and in multiple cases involves Segment-2 resulting in antigenic shift. [ABSTRACT FROM AUTHOR]

Novel highly pathogenic avian influenza (HPAI) H5Nx viruses are predominantly circulating worldwide, with an increasing potential threat of an outbreak in humans. It remains largely unknown how the stably maintained HPAI H5N1 suddenly altered its neuraminidase (NA) to other NA subtypes, which resulted in the emergence and evolution of H5Nx viruses. Here, we found that a combination of four specific amino acid (AA) substitutions (S123P-T156A-D183N- S223 R) in the hemagglutinin (HA) protein consistently observed in the H5Nx markedly altered the NA preference of H5N1 viruses. These molecular changes in H5N1 impaired its fitness, particularly viral growth and the functional activities of the HA and NA proteins. Among the AA substitutions identified, the T156A substitution, which contributed to the NA shift, also dramatically altered the antigenicity of H5N1 viruses, suggesting an occurrence of antigenic drift triggered by selective pressure. Our study shows the importance of how HA and NA complement each other and that antigenic drift in HA can potentially cause a shift in the NA protein in influenza A virus evolution.

Influenza A (IAV) is a major human respiratory pathogen that contributes to a significant threat to health security, worldwide. Despite vaccinations and previous immunisations through infections, humans can still be infected with influenza several times throughout their lives. This phenomenon is attributed to the antigenic changes of hemagglutinin (HA) and neuraminidase (NA) proteins in IAV via genetic mutation and reassortment, conferring antigenic drift and antigenic shift, respectively. Numerous findings indicate that slow antigenic drift and reassortment-derived antigenic shift exhibited by IAV are key processes that allow IAVs to overcome the previously acquired host immunity, which eventually leads to the annual re-emergence of seasonal influenza and even pandemic influenza, in rare occasions. As a result, current therapeutic options hit a brick wall quickly. As IAV remains a constant threat for new outbreaks worldwide, the underlying processes of genetic changes and alternative antiviral approaches for IAV should be further explored to improve disease management. In the light of the above, this review discusses the characteristics and mechanisms of mutations and reassortments that contribute to IAV's evolution. We also discuss several alternative RNA-targeting antiviral approaches, namely the CRISPR/Cas13 systems, RNA interference (RNAi), and antisense oligonucleotides (ASO) as potential antiviral approaches against IAV. [ABSTRACT FROM AUTHOR]

Bluetongue (BT), a viral disease of ruminants, is endemic throughout South Africa, where outbreaks of different serotypes occur. The predominant serotypes can differ annually due to herd immunity provided by annual vaccinations using a live attenuated vaccine (LAV). This has led to both wild-type and vaccine strains co-circulating in the field, potentially leading to novel viral strains due to reassortment and recombination. Little is known about the molecular evolution of the virus in the field in South Africa. The purpose of this study was to investigate the genetic diversity of field strains of BTV in South Africa and to provide an initial assessment of the evolutionary processes shaping BTV genetic diversity in the field. Complete genomes of 35 field viruses belonging to 11 serotypes, collected from different regions of the country between 2011 and 2017, were sequenced. The sequences were phylogenetically analysed in relation to all the BTV sequences available from GenBank, including the LAVs and reference strains, resulting in the analyses and reassortment detection of 305 BTVs. Phylogenomic analysis indicated a geographical selection of the genome segments, irrespective of the serotype. Based on the initial assessment of the current genomic clades that circulate in South Africa, the selection for specific clades is prevalent in directing genome segment reassortment, which seems to exclude the vaccine strains and in multiple cases involves Segment-2 resulting in antigenic shift.

Keywords: H5N1; spillover; epidemic; avian influenza A; genetic drift; antigenic drift; antigenic shift EN H5N1 spillover epidemic avian influenza A genetic drift antigenic drift antigenic shift 323 325 3 05/16/23 20230601 NES 230601 Main text Three years after the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic [[1]], there are several concerns about a new potential threat - the Avian Influenza A H5N1. H5N1, spillover, epidemic, avian influenza A, genetic drift, antigenic drift, antigenic shift Assessment of risk associated with recent influenza A(H5N1) clade 2.3.4.4b viruses. [Extracted from the article]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus. [ABSTRACT FROM AUTHOR]

Influenza is an important public health concern. We propose a new real-time influenza-like illness (ILI) surveillance system that utilizes a nationwide prospective drug utilization monitoring in Korea. We defined ILI-related claims as outpatient claims that contain both antipyretic and antitussive agents and calculated the weekly rate of ILI-related claims, which was compared to weekly ILI rates from clinical sentinel surveillance data during 2014–2018. We performed a cross-correlation analysis using Pearson's correlation, time-series analysis to explore actual correlations after removing any dubious correlations due to underlying non-stationarity in both data sets. We used the moving epidemic method (MEM) to estimate an absolute threshold to designate potential influenza epidemics for the weeks with incidence rates above the threshold. We observed a strong correlation between the two surveillance systems each season. The absolute thresholds for the 4-years were 84.64 and 86.19 cases per 1000claims for claims data and 12.27 and 16.82 per 1000 patients for sentinel data. The epidemic patterns were more similar in the 2016–2017 and 2017–2018 seasons than the 2014–2015 and 2015–2016 seasons. ILI claims data can be loaded to a drug utilization review system in Korea to make an influenza surveillance system. [ABSTRACT FROM AUTHOR]

The study aims to review the recent concepts of Antigenic shift and drift in viral strains of Influenza and Corona. The strains of Influenza and Corona are constantly under mutation. These viral envelopes compose of surface antigens like haemagglutinin - HA, Neuraminidase NA-antigens respectively. Hence, any minor changes in the genes responsible for the HA and NA proteins is termed as an antigenic drift. However, if it involves a major rapid change then it is referred to as an antigenic shift. In response to such changes, the body's immune system adapts accordingly and produces antibodies against the mutated antigen.A thorough literature search was attempted to consolidate recent concepts of antigenic shift and drift of Corona and Influenza using search engines like Pubmed, Google Scholar. The articles were screened and then were analysed for obtaining significant conclusions. The recent genetic analysis performed by Lancet et al reveals similarity in receptors (receptor binding protein) in SARS and those present in bats. Further, it is also predicted that recent genetic recombination of the earlier corona strains might have contributed to SARS - CoV -2. The propagation of antigenic shift and drift is reported to be similar to that of HINI Influenza strains in recent studies. [ABSTRACT FROM AUTHOR]

A virus is a non-living organism and it depends upon the host cell for its functions. A viral protein is the product of the virus and consists of a capsid and the envelope and performs a complex mechanism. A viral receptor can be defined as a host cell surface component that is recognized by the virus as a gateway entry into the cell. The interactions with viral receptors are mediated by viral attachment proteins called virions or glycoproteins. All the virus needs to bind with a specific receptor molecule on the surface of target cells to initiate infection. Virus-receptor binding is highly specific. One of the most remarkable receptors is present in the influenza virus. They belong to the family Orthomyxoviridae and cause respiratory symptoms. They are spherical and enveloped having ssRNA. The physical interaction with its receptors Hemagglutinin and Neuraminidase elicit infections. It also has a highly specific binding and can even produce cross inflections due to mutations. A virus has both natural and unnatural hosts. The effect of receptor damage on hosts causes multiple diseases. The cell target shift plays one of the major roles in cross-transmission and recognition of a specific subtype. The different viral receptors present in the cell surface of influenza are discussed in this study. It is useful for clinical assessment and future studies. [ABSTRACT FROM AUTHOR]

Tropical theileriosis caused by Theileria annulata infection is a significant livestock disease affecting cattle health and productivity resulting in substantial monetary losses in several countries. Despite the use of an effective vaccine for disease control still, a high incidence of infection is reported from India. One of the many reasons behind the ineffective disease control can be the existence of genetically diverse T. annulata parasite population in India. Therefore, studies focusing on understanding the genotypes are warranted. In this study, we have performed a genetic analysis of the Indian T. annulata field cell lines and the vaccine line using microsatellite markers, Genotyping based sequencing (GBS) and tams1 gene polymorphism. The degree of allelic diversity and multiplicity of the infection was determined to be high in the Indian population. No geographical sub-structuring and linkage disequilibrium were observed in the population. High population diversity was found which were similar with countries like Oman, Tunisia, and Turkey in contrast to Portugal and China. The presence of multiple genotypes as determined by microsatellite marker genotyping, GBS analysis and tams1 gene polymorphism point toward a panmictic parasite population in India. These findings are the first report from India which would help in understanding the evolution and diversity of the T. annulata population in the country and can help in designing more effective strategies for controlling the disease. [ABSTRACT FROM AUTHOR]

The human respiratory syncytial virus (hRSV) is the leading cause of pneumonia in infants and produces a significant burden in the elderly. It can also infect and produce disease in otherwise healthy adults and recurrently infect those previously exposed to the virus. Importantly, recurrent infections are not necessarily a consequence of antigenic variability, as described for other respiratory viruses, but most likely due to the capacity of this virus to interfere with the host's immune response and the establishment of a protective and long-lasting immunity. Although some genes encoded by hRSV are known to have a direct participation in immune evasion, it seems that repeated infection is mainly given by its capacity to modulate immune components in such a way to promote non-optimal antiviral responses in the host. Importantly, hRSV is known to interfere with dendritic cell (DC) function, which are key cells involved in establishing and regulating protective virus-specific immunity. Notably, hRSV infects DCs, alters their maturation, migration to lymph nodes and their capacity to activate virus-specific T cells, which likely impacts the host antiviral response against this virus. Here, we review and discuss the most important and recent findings related to DC modulation by hRSV, which might be at the basis of recurrent infections in previously infected individuals and hRSV-induced disease. A focus on the interaction between DCs and hRSV will likely contribute to the development of effective prophylactic and antiviral strategies against this virus. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) has a segmented genome, which (i) allows for exchange of gene segments in coinfected cells, termed reassortment, and (ii) necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Here, we evaluated the extent to which packaging signals prevent reassortment events that would raise concern for pandemic emergence. Specifically, we tested the compatibility of hemagglutinin (HA) packaging signals from H5N8 and H7N9 avian IAVs with a human seasonal H3N2 IAV. By evaluating reassortment outcomes, we demonstrate that HA segments carrying H5 or H7 packaging signals are significantly disfavored for incorporation into a human H3N2 virus in both cell culture and a guinea pig model. However, incorporation of the heterologous HAs was not excluded fully, and variants with heterologous HA packaging signals were detected at low levels in vivo, including in naïve contact animals. This work indicates that the likelihood of reassortment between human seasonal IAV and avian IAV is reduced by divergence in the RNA packaging signals of the HA segment. These findings offer important insight into the molecular mechanisms governing IAV emergence and inform efforts to estimate the risks posed by H7N9 and H5N8 subtype avian IAVs. [ABSTRACT FROM AUTHOR]

Aim. To investigate the mechanisms of variability of the influenza virus.Discussion. Influenza is one of the most significant problems facing the health care system. Human influenza causes a number of social and economic problems: mortality in high-risk groups, increasing in the load on personnel agencies health and reduced manpower. Features of the influenza virus genome enable the pathogen to cause seasonal epidemics each year, despite the preventive measures (vaccination) and using of specific antiviral drugs.Conclusion. Variability of the influenza virus genome is provided by antigenic drift, antigenic shift and recombination. This mechanisms of the variability of influenza virus that allow to remain a highly contagious infectious agent able to infect a large number of host species and cause significant problems as a result of epidemics and pandemics.

The small molecule compounds like pesticide, veterinary drug, bio-toxin, and heavy metal are widely found in animals, plants, soil, etc. Excessive compounds residues will have a bad influence on human health and the environment. Thus, it is extremely urgent that can detect the small molecules simultaneously. At present, many researches of simultaneous detection for small molecules using the method of an immunoassays have been reported thanks to its advantages of fast speed, simple operation, and high specificity. The small molecules have only one antigenic determinant, so the competitive immunoassay is the main method for small molecule compounds detection. In this paper, our main job is to describe the development of immunoassay for multi-residue detection of small molecule compounds and introduce three ways to complete the analysis of multi-residue immunoassay of small molecule compounds. We also summarize deficiencies and make an expectation of the immunoassays. [ABSTRACT FROM AUTHOR]

Abstract Staphylococcus saprophyticus is a gram-positive microorganism responsible for urinary tract infections (UTIs). Although some virulence factors are characterized, such as urease, autolysins, adhesins and hemagglutinins, large-scale proteomic studies have not been performed within this species. We performed the characterization of the exoproteome from three S. saprophyticus strains: the reference strain ATCC 15,305, a non-capsular strain 7108 and the 9325 strain containing a thick capsule which were cultured in BHI medium and culture supernatants were analysed by using mass spectrometry approach. We observed a core of 72 secreted proteins. In addition, it was possible to detect diversity in the protein profiles of the exoproteomes. Interestingly, strain 7108 presented no secretion of three antigenic proteins, including the classical SsaA antigen. In addition, the level of antigenic proteins secreted by strain 9325 was higher than in ATCC 15,305. This result was confirmed by Western blot analysis using anti-SsaA polyclonal antibodies, and no production/ secretion of SsaA was detected in strain 7108. Transcriptional data shows that 7108 strain produces transcripts encoding SsaA, suggesting post-transcriptional regulation occurs in this strain. Moreover, when compared with the other strains that were analyzed, it was possible to detect higher levels of proteases secreted by strain 7108 and higher levels of antigenic proteins and transglycosylases secreted by 9325 strain. The results reveal diversity in protein secretion among strains. This research is an important first step towards understanding the variability in S. saprophyticus exoproteome profile and could be significant in explaining differences among strains. [ABSTRACT FROM AUTHOR]

‘National foot-and-mouth disease (FMD) control programme’ is being implemented in India and therefore predicting vaccine match is a key surveillance task. Recently, a considerable proportion of field viruses (75.6%) showed antigenic drift from the existing serotype A vaccine strain A IND 40/2000 necessitating search for an alternate strain. Here, antigenic relationship (‘r 1 ’ value) of 87 field viruses with each of the 8 candidate strains was estimated by virus neutralization test. A IND 27/2011 strain emerged to be the one with the widest spectrum of antigenic coverage showing ‘r 1 ’ value of more than 0.3 with 81.6% of field strains. It achieved a reasonably high titre of log 10 7.5 TCID 50 /ml in BHK-21 suspension cell which was accompanied by positive charge gaining substitutions (E 82 –K and E 131 –K in VP2) thought to have adaptive significance. However, potency trial remains to be conducted before A IND 27/2011 finds a place in the vaccine formulation. [ABSTRACT FROM AUTHOR]

Numerous modern technological and scientific advances have changed the vaccine industry. However, nearly 70 years of influenza vaccine usage have passed without substantial changes in the underlying principles of the vaccine. The challenge of vaccinating against influenza lies in the constantly changing nature of the virus itself. Influenza viruses undergo antigenic evolution through antigenic drift and shift in their surface glycoproteins. This has forced frequent updates of vaccine antigens to ensure that the somewhat narrowly focused vaccine-induced immune responses defend against circulating strains. Few vaccine production systems have been developed that can entertain such constant changes. Although influenza virus infection induces long-lived immunologic memory to the same or similar strains, most people do not encounter the same strain repeatedly in their lifespan, suggesting that enhancement of natural immunity is required to improve influenza vaccines. It is clear that transformative change of influenza vaccines requires a rethink of how we immunize. In this study, we review the problems associated with the changing nature of the virus, and highlight some of the approaches being employed to improve influenza vaccines. [ABSTRACT FROM AUTHOR]

The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host’s first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.

In this paper, a delayed virus infection model with cell-to-cell transmission and CTL immune response is investigated. In the model, time delay is incorporated into the CTL response. By constructing Lyapunov functionals, global dynamical properties of the two boundary equilibria are established. Our results show that time delay in the CTL response process may lead to sustained oscillation. To further investigate the nature of the oscillation, we apply the method of multiple time scales to calculate the normal form on the center manifold of the model. At the end of the paper, numerical simulations are carried out, which support our theoretical results. [ABSTRACT FROM AUTHOR]

The influenza virus H1N1 has been prevalent all over the world for nearly a century. Many studies on its evolutionary history, substitution rate and antigenicity-associated sites have been done with small datasets. To have a complete view, we analysed 3171 full-length HA sequences from human H1N1 viruses sampled from 1918 to 2016, and discovered a new clade has formed with sequences isolated in Iran. Based on genetic distance calculations, we revealed an uneven evolutionary rate among sequences isolated in different years. We also found that the HA1 fragment of the new clade is like that of viruses that existed in the 1930s, while the HA2 fragment is closely associated with strains isolated after the 2009 pandemic. This new, “mixed” HA sequence indicates a cryptic antigenic shift event occurred, and it should draw more attention to the new clade identified from sequences from Iran. [ABSTRACT FROM AUTHOR]

Recurrent influenza epidemics and occasional pandemics are one of the most important global public health concerns and are major causes of human morbidity and mortality. Influenza viruses can evolve through antigen drift and shift to overcome the barriers of human immunity, leading to host adaption and transmission. Mechanisms underlying this viral evolution are gradually being elucidated. Vaccination is an effective method for the prevention of influenza virus infection. However, the emergence of novel viruses, including the 2009 pandemic influenza A (H1N1), the avian influenza A virus (H7N9), and the highly pathogenic avian influenza A virus (HPAI H5N1), that have infected human populations frequently in recent years reveals the tremendous challenges to the current influenza vaccine strategy. A better vaccine that provides protection against a wide spectrum of various influenza viruses and long-lasting immunity is urgently required. Here, we review the evolutionary changes of several important influenza proteins and the influence of these changes on viral antigenicity, host adaption, and viral pathogenicity. Furthermore, we discuss the development of a potent universal influenza vaccine based on this knowledge. [ABSTRACT FROM AUTHOR]

Antigenic drift and shift of influenza strains underscore the need for broadly protective influenza vaccines. One strategy is to design immunogens that elicit B cell responses against conserved epitopes on the hemagglutinin (HA) stem. To better understand the elicitation of HA stem--targeted B cells to group 1 and group 2 influenza subtypes, we compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem--specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1--specific. Immunoglobulin repertoire analysis of HA-specific B cells indicated that the H7N9 and H5N1 vaccines induced genetically similar cross-group HA stem--binding B cells, albeit at a much higher frequency upon H7N9 vaccination. These data suggest that a group 2--based stem immunogen could prove more effective than a group 1 immunogen at eliciting broad cross-group protection in humans. [ABSTRACT FROM AUTHOR]

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes. IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution. [ABSTRACT FROM AUTHOR]

The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing. An increase (p<0.0001) in serum KLH-specific IgG level was measured between days 21 and days 28, 35 and 42 in vaccinated foals from non-vaccinated mares. In vaccinated foals from vaccinated mares, serum KLH-specific IgG levels tended to increase at day 42 (p = 0.07). In contrast, serum influenza-specific IgG levels rapidly decreased (p≤0.05) in vaccinated foals from vaccinated mares within the study period. Nevertheless, IGHM and IGHG sequences were detected in KLH- and influenza- sorted B cells of vaccinated foals, independently of maternal vaccination status. Immunoglobulin nucleotide germline identity, IGHV gene usage and CDR length of antigen-specific IGHG sequences in B cells of vaccinated foals revealed a diverse immunoglobulin repertoire with isotype switching that was comparable between groups and to vaccinated mares. The low expression of CD27 memory marker in antigen-specific B cells, and of cytokines in peripheral blood mononuclear cells upon in vitro immunogen stimulation indicated limited lymphocyte population expansion in response to vaccine during the study period. [ABSTRACT FROM AUTHOR]

To asses the effect of turmeric (Curcuma longa) supplementation on antioxidants and immunity of broiler chickens, seventy five run day old coloured synthetic broiler chicks were randomly divided into 3 groups (25 chicks per each) of mixed sex. Group I served as control (without any supplementation), whereas birds in groups II and III were supplemented with 0.5% and 1.0% Curcuma longa powder respectively and the trail was lasted for 7 weeks. Blood samples were collected at the end of the experiment to study the antioxidant enzyme status and immunity of birds. The results indicated that addition of Curcuma longa powder caused significant (P<0.05) increase in antioxidant enzyme status of birds. The cellular immune response of broiler birds to phytoheamagltinin-P and antibody titre to sheep red blood cells was significantly (P < 0.05) higher in treated group than unsupplemented control birds. The present results confirmed the beneficial effects of dietary Curcuma longa powder to improve antioxidant enzymes and immune status of broiler chickens. [ABSTRACT FROM AUTHOR]

The genome of virulent strains may possess the ability to mutate by means of antigenic shift and/or antigenic drift as well as being resistant to antibiotics with time. The outbreak and spread of these virulent diseases including avian influenza (H1N1), severe acute respiratory syndrome (SARS-Corona virus), cholera (Vibrio cholera),tuberculosis (Mycobacterium tuberculosis), Ebola hemorrhagic fever (Ebola Virus) and AIDS (HIV-1) necessitate urgent attention to develop diagnostic protocols and assays for rapid detection and screening. Rapid and accurate detection of first cases with certainty will contribute significantly in preventing disease transmission and escalation to pandemic levels. As a result, there is a need to develop technologies that can meet the heavy demand of an all-embedded, inexpensive, specific and fast biosensing for the detection and screening of pathogens in active or latent forms to offer quick diagnosis and early treatments in order to avoid disease aggravation and unnecessary late treatment costs. Nucleic acid aptamers are short, single-stranded RNA or DNA sequences that can selectively bind to specific cellular and biomolecular targets. Aptamers, as new-age bioaffinity probes, have the necessary biophysical characteristics for improved pathogen detection. This article seeks to review global pandemic situations in relation to advances in pathogen detection systems. It particularly discusses aptameric biosensing and establishes application opportunities for effective pandemic monitoring. Insights into the application of continuous polymeric supports as the synthetic base for aptamer coupling to provide the needed convective mass transport for rapid screening is also presented. [ABSTRACT FROM PUBLISHER]

Flavobacterium columnare causes columnaris disease in freshwater fish. In the present study, the antigenic regions of five outer membrane proteins (OMPs), including zinc metalloprotease, prolyl oligopeptidase, thermolysin, collagenase and chondroitin AC lyase, were bioinformatically analyzed, fused together, and then expressed as a recombinant fusion protein in Escherichia coli. The expressed protein of 95.6 kDa, as estimated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was consistent with the molecular weight deduced from the amino acid sequence. The purified recombinant protein was used to vaccinate the grass carp, Ctenopharyngodon idella. Following vaccination of the fish their IgM antibody levels were examined, as was the expression of IgM, IgD and IgZ immunoglobulin genes and other genes such as MHC Iα and MHC IIβ, which are also involved in adaptive immunity. Interleukin genes ( IL), including IL-1β, IL-8 and IL-10, and type I and type II interferon ( IFN) genes were also examined. At 3 and 4 weeks post-vaccination (wpv), significant increases in IgM antibody levels were observed in the fish vaccinated with the recombinant fusion protein, and an increase in the expression levels of IgM, IgD and IgZ genes was also detected following the vaccinations, thus indicating that an adaptive immune response was induced by the vaccinations. Early increases in the expression levels of IL and IFN genes were also observed in the vaccinated fish. At four wpv, the fish were challenged with F. columnare, and the vaccinated fish showed a good level of protection against this pathogen, with 39% relative percent survival (RPS) compared with the control group. It can be concluded, therefore, that the five OMPs, in the form of a recombinant fusion protein vaccine, induced an immune response in fish and protection against F. columnare. [ABSTRACT FROM AUTHOR]

After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of TBI (> 1 year after injury). Using a closed-head injury model of TBI in mice, we showed by MRI scans that TBI caused substantial degeneration at the lesion site within a few weeks and these did not expand significantly thereafter. However, chronic alterations in neurons were observed, with reduced dendritic spine density lasting >1 year after injury. In parallel, we found a long-lasting inflammatory response throughout the entire brain. Deletion of one allele of CX3CR1, a chemokine receptor, limited infiltration of peripheral immune cells and largely prevented the chronic degeneration of the injured brain and provided a better functional recovery in female, but not male, mice. Therefore, targeting persistent neuroinflammation presents a new therapeutic option to reduce chronic neurodegeneration. [ABSTRACT FROM AUTHOR]

As the number of drug-resistant influenza viruses continues to increase, antivirals with novel mechanisms of action are urgently needed. Among the two classes of FDA-approved antiviral drugs, neuraminidase (NA) inhibitors, oseltamivir, zanamivir, and peramivir, are currently the only choice for the prevention and treatment of influenza virus infection. Due to the antigenic drift and antigenic shift, it will only be a matter of time before influenza viruses become completely resistant to these NA inhibitors. In pursuing the next generation of antiviral drugs with complementary mechanisms of action to those of the NA inhibitors, we have identified a natural product, cyclosporine A (CsA) ( 1 ), as a desired drug candidate. In this study, we discovered that CsA ( 1 ) and its analogs have broad-spectrum antiviral activity against multiple influenza A and B strains, including strains that are resistant to either NA or M2 inhibitors or both. Moreover, CsA ( 1 ) displays a high in vitro genetic barrier of drug resistance than oseltamivir carboxylate Mechanistic studies revealed that CsA ( 1 ) acts at the intermediate step of viral replication post viral fusion. Its antiviral mechanism is independent of inhibiting the isomerase activity of cyclophilin A (CypA), and CsA ( 1 ) has no effect on the viral polymerase activity The potent antiviral efficacy of CsA ( 1 ), coupled with the high in vitro genetic barrier of drug resistance and novel mechanism of action, renders CsA ( 1 ) a promising anti-influenza drug candidate for further development. [ABSTRACT FROM AUTHOR]

Background Factors, such as age, comorbidities, vaccine type, herd immunity, previous influenza exposure, and antigenic shift may impact the immune response to the influenza vaccine, protection against circulating strains, and antibody waning. Evaluating vaccine effectiveness (VE) is important for informing timing of vaccine administration and evaluating overall vaccine benefit. Methods VE was assessed using febrile respiratory illness surveillance among Department of Defense non-active duty beneficiaries from influenza seasons 2010–2011 through 2013–2014. Respiratory specimens were taken from participants meeting the case definition and tested by polymerase chain reaction for influenza. VE was calculated using logistic regression and by taking 1 minus the odds ratio of being vaccinated in the laboratory confirmed positive influenza cases versus laboratory confirmed negative controls. Results This study included 1486 participants. We found an overall adjusted VE that provided significant and fairly consistent protection ranging from 54% to 67% during 0–180 days postvaccination. This VE dropped to −11% (95% confidence interval: −102% to 39%) during 181–365 days. Conclusions Our study found moderate VE up to 6 months postvaccination. Since the influenza season starts at different times each year, optimal timing is difficult to predict. Consequently, early influenza vaccination may still offer the best overall protection. [ABSTRACT FROM AUTHOR]

In recent years a number of studies have brought attention to the role of positive selection during the evolution of antigenic escape by influenza strains. Particularly, the identification of positively selected sites within antigenic domains of viral surface proteins has been used to suggest that the evolution of viral-host receptor binding specificity is driven by selection. Here we show that, following the 1918 outbreak, the antigenic sites of the hemagglutinin (HA) viral surface protein and the stalk region of neuraminidase became substitution hotspots. The hotspots show similar patterns of nucleotide substitution bias at synonymous and nonsynonymous sites. Such bias imposes directionality in amino acid replacements that can influence signals of selection at antigenic sites. Our results suggest that the high accumulation of substitutions within the antigenic sites of HA can explain not only cases of antigenic escape by antigenic drift but also lead to occasional episodes of viral extinction. [ABSTRACT FROM AUTHOR]

Entomopathogenic nematodes are symbiotically associated with bacteria and widely used in biological control of insect pests. The interference of symbiotic bacteria with insect host immune responses is fairly well documented. However, knowledge of mechanisms regulating parasite-host interactions still remains fragmentary. In this study, we used nematode ( Steinernema carpocapsae and Heterorhabditis bacteriophora) cuticles and Galleria mellonella larvae as parasite-host model, focused on the changes of innate immune parameters of the host in the early phase of nematode cuticle infection and investigated the role of eicosanoid biosynthesis pathway in the process. The results showed that injection of either S. carpocapsae or H. bacteriophora cuticles into the larval hemocoel both resulted in significant decreases in the key innate immune parameters (e.g., hemocyte density, microaggregation, phagocytosis and encapsulation abilities of hemocyte, and phenoloxidase and antibacterial activities of the cell-free hemolymph). Our study indicated that the parasite cuticles could actively suppress the innate immune response of the G. mellonella host. We also found that treating G. mellonella larvae with dexamethasone and indomethacin induced similar depression in the key innate immune parameters to the nematode cuticles. However, these effects were reversed when dexamethasone, indomethacin, or nematode cuticles were injected together with arachidonic acid. Additionally, we found that palmitic acid did not reverse the influence of the dexamethasone, indomethacin, or nematode cuticles on the innate immune responses. Therefore, we inferred from our results that both S. carpocapsae and H. bacteriophora cuticles inhibited eicosanoid biosynthesis to induce host immunodepression. [ABSTRACT FROM AUTHOR]

Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. [ABSTRACT FROM AUTHOR]

There are no studies investigating the role of nutritional status and immunity associated with Jorge Lobo's disease. The objective of this study was to evaluate the effects of protein-calorie malnutrition on the immune response of BALB/c mice inoculated with Lacazia loboi. In this study,the animals were divided into four groups: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. The animals of groups G1 and G2 were submitted to malnutrition for 20 days and once installed the animals were inoculated intradermally into the footpad. After 4 months, they were euthanised for the isolation of peritoneal lavage cells and removal of the footpad. The production of IL-2, IL-4, IL-10, IL-12, IFN-γ, TNF-α, H2O2 and nitric oxide (NO) was evaluated in the peritoneal lavage cells. The footpad was evaluated regarding the size of macroscopic lesions, number of fungi and viability index. The results showed that the infection did not exert great influence on the body weight of the mice and previous malnutrition was an unfavourable factor for viability index, number of fungi, macroscopic lesion size in the footpad and production of H2O2, NO, IL-12, IL-10 and IFN-γ, suggesting that malnutrition significantly altered fungal activity and peritoneal cells. The results suggest considerable interaction between nutrition and immunity in Jorge Lobo's disease. [ABSTRACT FROM AUTHOR]

Pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. Recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. Interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. In particular, if we are to understand the role strain replacement plays in vaccinated settings, it will be essential to understand how strains or variants of pertussis interact. Here we explore under what conditions we would expect strain replacement to be of concern in pertussis. We develop a dynamic transmission model that allows for coinfection between Bordetella pertussis (the main causative agent of pertussis) and a strain or variant unaffected by the vaccine. We incorporate both neutrality (in the sense of ecological/population genetic neutrality) and immunity into the model, leaving the specificity of the immune response flexible. We find that strain replacement may be considerable when immunity is non-specific. This is in contrast to previous findings where neutrality was not considered. We conclude that the extent to which models reflect ecological neutrality can have a large impact on conclusions regarding strain replacement. This will likely have onward consequences for estimates of vaccine efficacy and cost-effectiveness. [ABSTRACT FROM AUTHOR]