Efficacy of multivalent recombinant herpesvirus of turkey vaccines against high pathogenicity avian influenza, infectious bursal disease, and Newcastle disease viruses

Vaccines are an essential tool for the control of viral infections in domestic animals. We generated recombinant vector herpesvirus of turkeys (vHVT) vaccines expressing computationally optimized broadly reactive antigen (COBRA) H5 of avian influenza virus (AIV) alone (vHVT-AI) or in combination with virus protein 2 (VP2) of infectious bursal disease virus (IBDV) (vHVT-IBD-AI) or fusion (F) protein of Newcastle disease virus (NDV) (vHVT-ND-AI). In vaccinated chickens, all three vHVT vaccines provided 90–100% clinical protection against three divergent clades of high pathogenicity avian influenza viruses (HPAIVs), and significantly decreased number of birds and oral viral shedding titers at 2 days post-challenge compared to shams. Four weeks after vaccination, most vaccinated birds had H5 hemagglutination inhibition antibody titers, which significantly increased post-challenge. The vHVT-IBD-AI and vHVT-ND-AI vaccines provided 100% clinical protection against IBDVs and NDV, respectively. Our findings demonstrate that multivalent HVT vector vaccines were efficacious for simultaneous control of HPAIV and other viral infections.info:eu-repo/semantics/publishedVersio

Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log10 mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boostinfo:eu-repo/semantics/publishedVersio

Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.info:eu-repo/semantics/publishedVersio

Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus

Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has produced negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccines (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then challenged three weeks later with H7N3 HPAI virus (A/chicken/Jalisco/CPA-37905/2015). The rFPV-H7/3002 vaccine conferred 100% protection against mortality and morbidity, and significantly reduced virus shed titers from the respiratory and gastrointestinal tracts. In contrast, 100% of sham and rFPV-H7/2155 vaccinated birds shed virus at higher titers and died within 4 days. Pre- (15/20) and post- (20/20) challenge serum of birds vaccinated with rFPV-H7/3002 had antibodies detectable by hemagglutination inhibition (HI) assay using challenge virus antigen. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but all birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). One possible explanation for differences in vaccines efficacy is the antigenic drift between circulating viruses and vaccines. Molecular analysis demonstrated that the Mexican H7N3 strains have continued to rapidly evolve since 2012. In addition, we identified in silico three potential new N-glycosylation sites on the globular head of the H7 HA of A/chicken/Jalisco/CPA-37905/2015 challenge virus, which were absent in 2012 H7N3 outbreak virus. Our results suggested that mutations in the HA antigenic sites including increased glycosylation sites, accumulated in the new circulating Mexican H7 HPAIV strains, altered the recognition of neutralizing antibodies from the older vaccine strain rFPV-H7/2155. Therefore, the protective efficacy of novel rFPV-H7/3002 against recent outbreak Mexican H7N3 HPAIV confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus.info:eu-repo/semantics/publishedVersio

Clinical presentation, convalescence, and relapse of rocky mountain spotted fever in dogs experimentally infected via tick bite.

Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by R. rickettsii in North and South America. Domestic dogs are susceptible to infection and canine RMSF can be fatal without appropriate treatment. Although clinical signs of R. rickettsii infection in dogs have been described, published reports usually include descriptions of either advanced clinical cases or experimental infections caused by needle-inoculation of cultured pathogen rather than by tick bite. The natural progression of a tick-borne R. rickettsii infection has not been studied in sufficient detail. Here, we provide a detailed description of clinical, hematological, molecular, and serological dynamics of RMSF in domestic dogs from the day of experimental exposure to infected ticks through recovery. Presented data indicate that neither the height/duration of fever nor detection of rickettsial DNA in dogs' blood by PCR are good indicators for clinical prognosis. Only the apex and subsequent subsidence of neutrophilia seem to mark the beginning of recovery and allow predicting a favorable outcome in Rickettsia-infected dogs, even despite the continuing persistence of mucosal petechiae and skin rash. On the other hand the appropriate (doxycycline) antibiotic therapy of sufficient duration is crucial in prevention of RMSF relapses in dogs

Diverse infectivity, transmissibility, and pathobiology of clade 2.3.4.4 H5Nx highly pathogenic avian influenza viruses in chickens

ABSTRACTClade 2.3.4.4 Eurasian lineage H5Nx highly pathogenic avian influenza virus (HPAIV) has become the globally dominant clade and caused global outbreaks since 2014. The clade 2.3.4.4 viruses have evolved into eight hemagglutinin subgroups (2.3.4.4a-h). In this study, we evaluated the infectivity, pathobiology, and transmissibility of seven clade 2.3.4.4 viruses (two 2.3.4.4a, two 2.3.4.4b, one 2.3.4.4c and two 2.3.4.4e) in chickens. The two clade 2.3.4.4e viruses caused 100% mortality and transmissibility in chickens. However, clade 2.3.4.4a and c viruses showed 80–90% mortality and 67% transmissibility. Clade 2.3.4.4b viruses showed 100% mortality, but no transmission to co-housed chickens was observed based on lack of seroconversion. All the infected chickens died showing systemic infection, irrespective of subgroup. The results highlight that all the clade 2.3.4.4 HPAIVs used in this study caused high mortality in infected chickens, but the transmissibility of the viruses in chickens was variable in contrast to that of previous Eurasian-lineage H5N1 HPAIVs. Changes in the pathogenicity and transmissibility of clade 2.3.4.4 HPAIVs warrant careful monitoring of the viruses to establish effective control strategies

Bilateral testicular inflammation developed two weeks after the completion of a 16-day doxycycline treatment.

<p>Bilateral testicular inflammation developed two weeks after the completion of a 16-day doxycycline treatment.</p

IgG antibody titers in dogs infected with <i>Rickettsia rickettsii</i>.

<p>Shaded area marks the period of antibiotic treatment in dogs 424 and 664.</p

Histopathological and immunohistochemical evaluation in a dog with severe Rocky Mountain spotted fever.

<p><b>A</b> - Canine lung with lymphohistiocytic and neutrophilic vasculitis and interstitial leukocytosis (hematoxylin and eosin staining; original magnification ×400). <b>B</b> - Canine colon, submucosa with vasculitis with thrombosis (hematoxylin and eosin staining; original magnification ×400). <b>C</b> - Canine brainstem with nonsuppurative perivascular infiltrate and glial nodule (hematoxylin and eosin staining; original magnification ×400). <b>D</b> - Canine brainstem; Immunostaining of spotted fever group rickettsial antigens in multiple vessels, immunoalkaline phosphatase staining, naphthol fast red substrate with hematoxylin counterstain (original magnification ×400).</p

Temperature charts and detection of pathogen DNA in venous blood in dogs infected with <i>Rickettsia rickettsii</i>.

<p>(Shaded area marks the period of antibiotic treatment in dogs 424 and 664).</p