Reduced Virus Shedding Research Articles

Selenium nanoparticles enhance the efficacy of homologous vaccine against the highly pathogenic avian influenza H5N1 virus in chickens

A proper vaccination against avian influenza viruses in chicken can significantly reduce the risk of human infection. Egypt has the highest number of recorded humans highly pathogenic avian influenza (HPAI)-H5N1 infections worldwide despite the widespread use of homologous vaccines in poultry. Enhancing H5N1 vaccine efficacy is ultimately required to better control HPAI-H5N1. The aim of this study is to boost chicken immunity by combined with inactivated HPAI-H5N1 with selenium nanoparticles (SeNPs). The chickens groups 1–3 were fed diets supplemented with SeNPs concentrations (0.25, 0.5, and 1 mg/kg) for 3 weeks and then vaccinated (inactivated HPAI-H5N1). while groups 4,5 and 6 were fed with SeNPs free diets and administered with 0.5 ml of the vaccine combined with 0.02, 0.06, and 0.1 mg/dose of SeNPs and then all groups were challenged with homologous virus 3 weeks post-vaccination (WPV). Group 7, 8 were used as control positive and negative respectively. At 4, 5, and 6 WPV, antibody titer was considerably higher in the group fed a meal supplemented with 1 mg SeNPs/kg. In contrast, both methods of SeNPs supplementation significantly increased the Interleukin 2 (IL2), Interleukin 6 (IL6), and Interferon γ (IFNγ) expressions in the blood cells in a dose-dependent manner, with a higher expression observed in the group that was vaccinated with 0.1 mg/dose. After the challenge, all groups that received SeNPs via diet or vaccines dose showed significant reduction in viral shedding and milder inflammation in lung, trachea, spleen, and liver in addition to higher expression of IL2, IL6, and IFNγ, with the highest expression observed in the group that was vaccinated with 0.1 mg/dose compared the plain vaccinated group. The groups of 1 mg SeNPs/kg and combined vaccinated with 0.1 mg/dose showed the best vaccine efficacy. However, the group vaccinated with 0.1 mg/dose showed the earliest reduction in viral shedding. Overall, SeNPs supplementation in the diet and the administration of the vaccine formula with SeNPs could enhance vaccine efficacy and provide better protection against HPAI-H5N1 in chickens by enhancing cellular immunity and reducing inflammation. We recommend using SeNPs as a vaccine combination or feeding with diet to increase the immunity and vaccine efficacy against H5N1.

Potential Impact of Nirsevimab on RSV Transmission and Medically Attended Lower Respiratory Tract Illness Caused by RSV: A Disease Transmission Model.

IntroductionRespiratory syncytial virus (RSV) is associated with significant morbidity worldwide, especially among infants. We evaluated the potential impact of prophylactic nirsevimab, a monoclonal antibody, in infants experiencing their first RSV season, and the number of medically-attended lower respiratory tract infection episodes caused by RSV (RSV-MALRTI) in the USA.MethodsWe developed an age-structured, dynamic, deterministic compartmental model reflecting RSV natural history, incorporating USA demographic data and an age-specific contact matrix. We assumed either no effect of nirsevimab on transmission (scenario 1) or a 50% reduction of viral shedding (scenario 2). Model outcomes were RSV-MALRTIs, ICD-9 coded in the Marketscan® database by month. We focused on age groups corresponding to the first 2 years of life, during seven RSV seasons (2008–2015).ResultsScenario 1 illustrated the direct individual benefit when a universal immunization strategy is applied to all infants. In scenario 2, herd protection was observed across age groups, with 15.5% of all avoided cases due to reduced transmission; the greatest impact was in the youngest age group and a benefit was observed in those aged 65+ years.ConclusionThese preliminary data suggest that single-dose nirsevimab will benefit infants experiencing their first RSV season, with a potential increase in effectiveness dependent on nirsevimab’s mechanism of action.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00566-9.

Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine.

Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.

Development of a recombinant H9N2 influenza vaccine candidate against the Y280 lineage field virus and its protective efficacy

Since June 2020, a new H9N2 virus of the Y280 lineage has been epidemic in Korea. Initially, a Korean commercial vaccine against the Y280 and Y439 lineages of H9N2 was evaluated for use in SPF chickens. A single vaccination did not protect chickens against virus of the Y280 lineage, with no significant reduction in virus shedding and a 37.5% inhibition in virus recovery rate in cecal tonsil. rgHS314 was selected as a vaccine candidate, showing immunogenicity in SPF chickens, and was highly productive in eggs. Moreover, rgHS314 protected with high levels of protective immunity and significantly reduced virus shedding, with 100% and 83.3% inhibition of virus recovery in the cecal tonsil against homologous and heterologous challenge viruses, respectively. Taken together, these data suggest that a single vaccination with this recombinant vaccine candidate could elicit cross-reactive immune responses capable of protecting chickens against H9N2 viruses of the Y439 and Y280 lineages.

Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication.

Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses

Mammalian cells utilize a wide spectrum of pathways to antagonize the viral replication. These pathways are typically regulated by antiviral proteins and can be constitutively expressed but also exacerbated by interferon induction. A myriad of interferon-stimulated genes (ISGs) have been identified in mounting broad-spectrum antiviral responses. Members of the interferon-induced transmembrane (IFITM) family of proteins are unique among these ISGs due to their ability to prevent virus entry through the lipid bilayer into the cell. In the current study, we generated transgenic chickens that constitutively and stably expressed chicken IFITM1 (chIFITM1) using the avian sarcoma-leukosis virus (RCAS)-based gene transfer system. The challenged transgenic chicks with clinical dose 104 egg infective dose 50 (EID50) of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 (clade 2.2.1.2) showed 100% protection and significant infection tolerance. Although challenged transgenic chicks displayed 60% protection against challenge with the sub-lethal dose (EID50 105), the transgenic chicks showed delayed clinical symptoms, reduced virus shedding, and reduced histopathologic alterations compared to non-transgenic challenged control chickens. These finding indicate that the sterile defense against H5N1 HPAIV offered by the stable expression of chIFITM1 is inadequate; however, the clinical outcome can be substantially ameliorated. In conclusion, chIFITM proteins can inhibit influenza virus replication that can infect various host species and could be a crucial barrier against zoonotic infections.

Discrepancies in the efficacy of H5 inactivated avian influenza vaccines in specific-pathogen-free chickens against challenge with the Egyptian H5N8 clade 2.3.4.4 Group B virus isolated in 2018.

Background and Aim:Highly pathogenic avian influenza H5N8 virus of clade 2.3.4.4 was newly emerged to Egypt and firstly detected in carcasses of wild birds in November 2016. This study assessed the protection efficacy and virus shedding reduction of three different inactivated avian influenza (AI) H5 (H5N1, H5N2, and H5N3) commercial vaccines against challenge with two newly emerging highly pathogenic AI virus H5N8 Egyptian isolates in specific-pathogen-free (SPF) chicks.Materials and Methods:10-day-old SPF chicks (n=260) were divided into 20 groups (n=13). Groups 1-5 were vaccinated through the subcutaneous route (S/C) with 0.5 mL of H5N1 vaccine, Groups 6-10 were vaccinated (S/C) with 0.5 mL of H5N2 vaccine, and Groups 11-15 were vaccinated (S/C) with 0.5 mL of H5N3 vaccine. Positive control groups (16-19) were challenged at 25 and 31 days old (2 and 3 weeks post-vaccination [PV]) using H5N8 clade 2.3.4.4 A/duck/Egypt/F13666A/2017(H5N8) and H5N8 clade 2.3.4.4 A/chicken/Egypt/18FL6/2018(H5N8). Group 20 was left non-vaccinated as a control. All vaccinated groups were divided and challenged with both viruses at 25 and 31 days of age. The viral challenge dose was 0.1 mL of 106 EID50/0.1 mL titer/chick, and it was administered oronasally. All chicks were kept in isolators for 14 days after each challenge. Sera samples were collected weekly and at 2 weeks post-challenge (PC) to detect a humoral immune response. PC mortalities were recorded daily for 10 days to calculate the protection percentages. Tracheal swabs were collected from the challenged chicks in different groups at 3, 5, 7, and 10 days PC. Kidneys and spleens were collected at 3, 5, 7, and 10 days PC and kept in formalin for histopathological examination to assess lesions and severity scores. Tracheal swabs were inoculated in 10-day-old SPF embryonated chicken eggs for virus titration and to calculate shedding levels.Results:All studied vaccines displayed 70-100% protection within 10 days PC. Hemagglutination inhibition results from sera samples revealed antibody titers ranging from 0.6 to 5.4 log2 starting at 1-week PV with the highest titers at 4 weeks PV. Challenged SPF chickens exhibited a notable reduction in virus shedding, with an average of 1.5-2 log10, compared to control birds. Various histopathological lesions with different scores were detected.Conclusion:Our findings suggest that the inadequate virus shedding reduction and protection efficacy of studied vaccines were variable and that the type of vaccine to be used under field conditions should be reconsidered. Study of the variability between the Egyptian old emerged AI (AIV) 2017 H5N8 strains and the new emerging AIV 2018 H5N8 is required to achieve optimal protection and limit the current economic losses.

Immunogenicity and efficacy of a bivalent vaccine against infectious bronchitis virus

Infectious bronchitis (IB) is a highly contagious viral disease and is responsible for considerable economic losses in the poultry industry, worldwide. To mitigate the IB-associated losses, multiple vaccines are being applied in the sector with variable successes and thus necessitating the development of a potent vaccine to protect against the IB in the poultry. In the present study, we investigated a bivalent live attenuated vaccine consisting of IB virus (IBV) strain H120 (GI-1 lineage) and D274 (GI-12 lineage) to evaluate its protection against heterologous variant of IBV (GI-23 lineage) in chicken. Protection efficacy was evaluated based on the serology, clinical signs, survival rates, tracheal and kidney histopathology and the viral shedding. Results demonstrated that administering live H120 and D274 (named here Classivar®) vaccine in one day-old and 14 days-old provided 100 % protection. We observed a significant increase in the mean antibody titers, reduced virus shedding, and ameliorated histopathology lesions compared to routinely used vaccination regimes. These results revealed that usage of different IBV vaccines combination can successfully ameliorate the clinical outcome and pathology in vaccinated chicks especially after booster vaccination regime using Classivar®. In conclusions, our data indicate that Classivar® vaccine is safe in chicks and may serve as an effective vaccine against the threat posed by commonly circulating IBV strains in the poultry industry.

Therapeutic and Prophylactic Potential of FMD Virus-specific Polyvalent Immunoglobulins during an FMD Outbreak in Cattle

Foot and mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals worldwide. In the present study the therapeutic and prophylactic potential of polyclonal, polyvalent FMD virus-specific bovine antibodies has been investigated as a possible approach for rapid control, lessening of the severity of clinical signs and prophylactic protection of susceptible animals during FMD outbreaks. The prepared FMD virus-specific polyvalent immunoglobulins were concentrated, purified, filter sterilized (0.22nm) and its titer against the FMD virus serotypes, A, O and SAT2, was adjusted to 2.15, 2.25 and 2.10 log10 TCID50/ml, respectively. In an experimental FMDV induced infection, the immunoglobulin therapy was given 4 days post experimental infection. The effect of different doses of immunoglobulins (4, 6 and 8ml) the severity of the clinical signs, healing of lesions and virus shedding was determined. A dose of 8 ml (2.0 log10 TCID50/ml) of the prepared FMD virus-specific antibodies proved highly effective in reducing the severity of the clinical signs and inducing recovery within 48 - 96hrs post therapy, as compared with the control non-treated infected calves. A dose related recovery rate was recorded. Field trial was conducted and evaluated during the FMD outbreak in Egypt during 2016/2017. Significant reduction of the morbidity of the disease and 100% reduction of mortality were recorded. The prepared FMD virus-specific bovine polyvalent antibodies proved to be a drug of choice during FMD outbreaks protecting susceptible animals and inducing rapid recovery of diseased one associated with reducing clinical signs severity and reducing virus shedding.

A broad spectrum HVT-H5 avian influenza vector vaccine which induces a rapid onset of immunity

Current methods to combat highly pathogenic avian influenza (HPAI) outbreaks in poultry rely on stamping out and preventive culling, which can lead to high economic losses and invoke ethical resistance. Emergency vaccination could be an alternative as vaccination is one of the most efficient and cost-effective measures to protect poultry from HPAI infection, preventing spreading to other poultry and greatly reducing the potential transmission to humans. Current conventional inactivated AI vaccines may be useful for combating AI outbreaks, but do not fulfil all targets of an ideal AI vaccine, including mass applicability and rapid onset of immunity. We aimed to further investigate the potential of Herpesvirus of Turkeys (HVT) as a vector containing a recombinant H5 hemagglutinin of HPAI H5N1. This HVT-H5 vector was analysed in vitro, tested for onset of immunity against AI challenge, breadth of protection, reduction of virus shedding, and induction of both antibody and cellular responses in SPF layers or broiler chicks containing maternal derived antibodies (MDA+). In SPF layers HVT-H5 provided full protection to lethal challenges with 4 antigenically diverse HPAI H5N1 strains from 2 weeks post vaccination (w.p.v.), while in MDA+ birds full protection was provided from 3 w.p.v. to homologous challenge. Also shedding of challenge virus was reduced in both SPF and MDA+ birds. HVT-H5 induced a protective HI titre (≥4) to 11 HPAI H5N1 strains at 3 w.p.v. in 3-week-old SPF layers and to HPAI H5N8 A/ch/Neth/14015531/2014. Besides inducing a protective antibody response HVT-H5 also induced an influenza-specific T cell response. This data demonstrates that HVT-H5 vaccine appears to fulfil many of the criteria for an ideal AI vaccine including early onset of immunity, a broad protection, reduced virus shedding, protection in presence of AI-MDA and could be a useful tool in the combat of AI outbreaks worldwide.

Avian Influenza-Killed Vaccine on Tissue Distribution and Shedding of Avian Influenza Virus H9N2 in Ducklings.

Ducks play an important role in the transmission of avian influenza to poultry farms. Because of the importance of vaccination in reducing virus shedding, this study evaluated avian influenza-killed vaccine H9N2 on tissue distribution and shedding of avian influenza virus H9N2 in ducklings. One hundred-day-old ducklings were purchased and, after bleeding from 20 birds, were kept in four separate rooms under standard conditions. Groups 1 and 2 were vaccinated at 9 days, and groups 2 and 3 were challenged with 0.1 ml of allantoic fluid containing 105 EID50 (A/chicken/Iran/Aid/2013(H9)) virus intranasally at 30 days. Group 4 chicks were kept as the control group. Chicks were observed two times daily. On days 1, 3, 5, and 8 after inoculation, 3 chicks were randomly selected from each group and cloaca and trachea swabs samples were collected from each bird. Then the ducklings were euthanized and trachea, lung, spleen, intestine, liver, and brain tissue samples were collected for molecular detection. The virus was detected in the tissues and tracheal and cloacal swabs by polymerase chain reaction (PCR), and anti-AIV titres were measured by HI test. The results showed no clinical signs in the challenged groups. In the vaccinated challenged group, virus was detected only in cloacal swabs, but in the unvaccinated challenged group, virus was detected more in tracheal swabs than in cloacal swabs. In challenged-unvaccinated chicks, virus was detected in the trachea and lungs, and in challenged-vaccinated birds, virus was detected in the intestines. In conclusion, vaccinating ducks against the AI H9N2 virus reduced shedding and tissue distribution of AI viruses in challenged ducks.

Novel Inactivated Subtype B Avian Metapneumovirus Vaccine Induced Humoral and Cellular Immune Responses.

Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain LN16. Combined with a novel adjuvant containing immune-stimulating complexes (ISCOMs), the novel vaccine could induce high virus-specific and VN antibodies. In addition, it activated B and T lymphocytes and promoted the expression of IL-4 and IFN-γ. Importantly, boosting vaccination with the inactivated aMPV/B vaccine could provide 100% protection against aMPV/B infection with reduced virus shedding and turbinate inflammation. The protection efficacy could last for at least 6 months. This study yielded a novel inactivated aMPV/B vaccine that could serve as the first vaccine candidate in China, thus contributing to the control of aMPV/B and promoting the development of the poultry industry.

Identification of Efficacious Vaccines Against Contemporary North American H7 Avian Influenza Viruses

Five vaccines, including four inactivated, whole-virus water-in-oil adjuvanted vaccines and a commercial non-replicating alphavirus vectored RNA particle (RP) vaccine were evaluated in chickens for their ability to provide protection against challenge with a recent H7 highly pathogenic avian influenza virus (AIV) from the US (A/turkey/IN/1403-1/2016 H7N8). One of the inactivated vaccines and the RP vaccine were prepared with A/turkey/IN/16-01571-6/2016 H7N8 low pathogenic AIV (TK/IN/16), which is identical to the challenge virus, except for the proteolytic cleavage site of the HA protein. The remaining 3 inactivated vaccines were prepared with other North American H7 LPAIV viruses. Hemagglutination inhibition assay was used to evaluate the antigenic relationships among the vaccines and selected recent H7 AIV isolates. All five vaccines provided protection against mortality. The inactivated vaccines reduced virus shedding significantly at 2 and 4 days post challenge compared to sham vaccinated chickens. In contrast, the RP vaccine did not significantly reduce virus shedding. The inactivated vaccine prepared with TK/IN/16 elicited the highest antibody responses, which suggests this is a strong candidate for use as an antigen for North American H7 AIVs. Antigenic distance calculations showed that the four inactivated vaccine strains and other recent North American H7 isolates are antigenically similar, which suggests that the vaccines evaluated here would be similar enough to provide protection to other North American H7 AIVs. If future H7 outbreaks in poultry warrant vaccination, the field strain can be rapidly evaluated with these antigens and if adequately related, one of these characterized strains may be utilized.

Protection conferred by commercial NDV live attenuated and double recombinant HVT vaccines against virulent California 2018 Newcastle disease virus (NDV) in chickens

Vaccines against virulent Newcastle disease virus (NDV) are widely available and can be protective, but improved vaccination protocols are needed to prevent clinical disease and reduce virus circulation. The present study evaluated the efficacy of two commercial vaccines alone or in combination: a live attenuated NDV vaccine (LV) and a recombinant herpesvirus of turkeys vector expressing the fusion protein of NDV and the virus protein 2 of infectious bursal disease virus (rHVT-ND-IBD). Chickens were vaccinated with one of four vaccination protocols: live vaccine (LV) at 1 and 11 days of age (DOA), rHVT ND-IBD and LV at 1 DOA, rHVT ND-IBD at 1 DOA boosted with an LV at 11 DOA, and rHVT ND-IBD at 1 DOA. The vaccinated birds were challenged at different time points (3 or 4 weeks of age) with the California 2018 virus. The mortality, clinical signs, mean death time (MDT), humoral response before and after vaccination, and virus shedding after challenge were evaluated. All vaccination protocols were able to prevent mortality, reduce virus shedding, and induce antibody levels before the challenge at 3 and 4 weeks-old. Overall, the antibody levels before the challenge at 4 weeks were significantly higher in all groups vaccinated with the rHVT ND-IBD when compared to levels in 3 week old birds. The combination of recombinant rHVT ND-IBD with a live vaccine at one-day-old seems to be a better combination, due to the absence of clinical signs, higher antibody levels pre and post-challenge, and reduced virus shedding at any time point after the challenge at 3 or 4 weeks of age with the California 2018 virus.

Efficacy of a modified-live IBR-BVD-PI3-BRSV-Mannheimia haemolytica toxoid vaccine against challenge with virulent BHV-1 and PI3 viruses in calves 60 days of age

Efficacy of attenuated (att) bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza type-3 (PI3) viruses as antigen fractions in a modified-live virus (MLV) multivalent vaccine was evaluated following single, subcutaneous (SC) administration and intranasal (IN) challenge 28 days after vaccination, with either virulent BHV-1 or PI3 viruses in young calves. A total of 80 seronegative calves, 50 to 63 days of age at the time of vaccination, were used in 2 separate studies with 40 animals per study. Calves were allocated to 2 treatment groups with 20 animals per group which received either a single dose of a MLV IBR-BVD-PI3-BRSV vaccine, Mannheimia haemolytica toxoid, or corresponding placebo formulation without targeted test antigen fractions attBHV-1 (Study 1) or attPI3 (Study 2). Incidence and duration of clinical signs associated with respiratory disease, rectal temperatures, virus shedding, and serologic responses were compared between treatment groups in each study to assess vaccine efficacy. The 5-way vaccine induced significantly higher (p<0.0001) virus neutralizing antibody responses and reduction in fever (p<0.0001), mean rectal temperatures, and lower incidence or shorter duration of clinical disease related to BHV-1 and PI3 infection than placebo-treated calves. Infectious bovine rhinotracheitis (IBR) disease, hallmark of BHV-1 infection, was observed in 95% of control calves and in only 10% of vaccinates. Vaccinated animals in Study 1 and Study 2 demonstrated a 98.8 and 98.9% reduction in virus shedding, respectively, and significantly (p<0.0001) shorter duration of virus shedding compared to control calves, demonstrating protective vaccine efficacy.

Evaluation for Efficacy of Commercially Available Vaccines Against Challenge with Newcastle Disease Virus Genotype VII in Broilers

The study evaluated the protective efficacy of commercially available live and inactivated Newcastle Disease Virus (NDV) vaccines. Moreover, study also highlighted the implementation of genotypically-matched NDV vaccines to the currently circulated velogenic genotype VII strain in commercial broilers vaccination regimes in Egypt. Serum antibodies level was assessed by Haemagglutination Inhibition method .Efficacy of Newcastle Disease killed and live vaccine was also determined using challenge test. Group A immunized with live attenuated and inactivated NDV vaccines genotype VII homologous to challenge virus provided non-significant protection against mortality .It proved 20 % as compared to 15 % mortalities in group B immunized with live attenuated and inactivated NDV vaccines genotype II heterologous to challenge virus. Meanwhile, group Aredult proved a significant reduction in viral shedding by cloacal swabs in compared with group B ,7 days post-challenge. Final Results of the present work concluded that live and inactivated NDV genotype VII vaccines antigenically matched to currently epidemic NDV genotype VII providing better control on virus shedding if compared with different genotype II vaccines. However, both vaccines provided good protection against likely virulent challenge in commercial broilers.

Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern?

Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern?

In Ovo Delivered Toll-Like Receptor 7 Ligand, Resiquimod Enhances Host Responses against Infectious Bronchitis Corona Virus (IBV) Infection.

Toll-like receptor (TLR) 7 ligand, resiquimod, has been studied as an adjuvant and antiviral agent against several pathogens in chicken. Yet, the effectiveness of resiquimod against infectious bronchitis virus (IBV) infection has not been evaluated. In this study, we investigated the effectiveness of resiquimod delivered pre-hatch (in ovo) against IBV infection post-hatch identifying key mechanisms involved in resiquimod driven immune activation. First, we found an upregulation of interleukin (IL)-1β and interferon (IFN)-γ mRNA levels and considerable expansions of macrophage and cluster of differentiation (CD) 8α+ T cell populations in lungs of chicken as early as day one post-hatch, following pre-hatch delivery of resiquimod. Second, we observed that resiquimod was able to act as an adjuvant when resiquimod was delivered pre-hatch along with an inactivated IBV vaccine. Finally, when the resiquimod pretreated one-day-old chickens were infected with IBV, reduction in viral shedding via oral and fecal routes was observed at 3 days post- infection. Overall, this study shows that the pre-hatch delivered resiquimod increases cell-mediated immune responses in lungs with an advantage of reduction in IBV shedding.

Herpes simplex virus 1 regulates β-catenin expression in TG neurons during the latency-reactivation cycle.

When herpes simplex virus 1 (HSV-1) infection is initiated in the ocular, nasal, or oral cavity, sensory neurons within trigeminal ganglia (TG) become infected. Following a burst of viral transcription in TG neurons, lytic cycle viral genes are suppressed and latency is established. The latency-associated transcript (LAT) is the only viral gene abundantly expressed during latency, and LAT expression is important for the latency-reactivation cycle. Reactivation from latency is required for virus transmission and recurrent disease, including encephalitis. The Wnt/β-catenin signaling pathway is differentially expressed in TG during the bovine herpesvirus 1 latency-reactivation cycle. Hence, we hypothesized HSV-1 regulates the Wnt/β-catenin pathway and promotes maintenance of latency because this pathway enhances neuronal survival and axonal repair. New studies revealed β-catenin was expressed in significantly more TG neurons during latency compared to TG from uninfected mice or mice latently infected with a LAT-/- mutant virus. When TG explants were incubated with media containing dexamethasone to stimulate reactivation, significantly fewer β-catenin+ TG neurons were detected. Conversely, TG explants from uninfected mice or mice latently infected with a LAT-/- mutant increased the number of β-catenin+ TG neurons in the presence of DEX relative to samples not treated with DEX. Impairing Wnt signaling with small molecule antagonists reduced virus shedding during explant-induced reactivation. These studies suggested β-catenin was differentially expressed during the latency-reactivation cycle, in part due to LAT expression.

Protective efficacy of the Newcastle disease virus genotype VII–matched vaccine in commercial layers

Newcastle disease virus (NDV) is a major threat to the poultry industry worldwide, with a diversity of genotypes associated with severe economic losses in all poultry sectors. Class II genotype VII NDV are predominant in the Middle East and Asia, despite intensive vaccination programs using conventional live and inactivated NDV vaccines. In Egypt, the disease is continuously spreading, causing severe economical losses in the poultry industry. In this study; the protective efficacy of a commercial, inactivated recombinant genotype VII NDV–matched vaccine (KBNP-C4152R2L strain) against challenge with the velogenic NDV strain (Chicken/USC/Egypt/2015) was evaluated in commercial layers. Two vaccination regimes were used; live NDV genotype II (LaSota) vaccine on days 10, 18, and 120, with either the inactivated NDV genotype II regime or inactivated NDV genotype VII–matched vaccine regime on days 14, 42, and 120. The 2 regimes were challenged at the peak of egg production on week 26. Protection by the 2 regimes was evaluated after experimental infection, based on mortality rate, clinical signs, gross lesions, virus shedding, seroconversion, and egg production schedule. The results show that these 2 vaccination regimes protected commercial layer chickens against mortality, but some birds showed mild clinical signs and reduced egg production temporarily. However, the combination of live NDV genotype II and recombinant inactivated genotype VII vaccines provided better protection against virus shedding (20% and 0% vs. 60% and 40%) as assessed in tracheal swabs and (20% and 0% vs. 20% and 20%) in cloacal swabs collected at 3 and 5 D post challenge (dpc), respectively. In addition, egg production levels in birds receiving the inactivated NDV genotype VII–matched vaccine regime and in those given inactivated genotype II vaccines were 76.6, 79, 82, and 87.4% and 77.7, 72.5, 69, and 82.5% at 7, 14, 21, and 28 dpc, respectively. The results of this study indicate that recombinant genotype-matched inactivated vaccine along with a live attenuated vaccine can reduce virus shedding and improve egg production in commercial layers challenged with a velogenic genotype VII virus under field conditions. This regime may ensure a proper control strategy in layers.