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Showing posts with the label animal models

Prior #infection with IBDV prolonged the shedding of a #mallard #H3N8 #influenza A virus (IAV) challenge from oropharyngeal cavity of some #chickens {...}

Abstract Infectious bursal disease virus (IBDV) is endemic worldwide and causes immunosuppression in chickens . We hypothesized that a previous history of IBDV in chickens would render them more susceptible to infection by influenza A viruses (IAVs) from aquatic waterfowl reservoirs . To model this, we inoculated 14 day old specific pathogen free (SPF) chickens with a low pathogenicity avian influenza (LPAI) virus strain from a mallard ( A/Mallard/Alberta/156/01 (H3N8) ) and compared replication and shedding between immunocompetent chickens and chickens that had immune dysregulation due to a prior IBDV infection with strain F52/70 (genogroup A1B1) at 2 days of age. The mallard IAV strain replicated in the upper respiratory tract of the chickens , and virus was shed from the oropharyngeal cavity , but there was no shedding from the cloaca , and no transmission to sentinel chickens . Replication of the mallard IAV in the chicken host was associated with amino acid substitutions in the po...

A Potent #Pandemic Avian #Influenza Virus #Vaccine Based on a 4th Generation Fully Deleted #Adenoviral #Vector

Abstract The GreVac system was developed as a fast and flexible plug-and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors . The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuramidase influenza genes . Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients' lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra mu...

A low pathogenic avian #influenza A/Mallard/South Korea/KNU2019-34/2019 (#H1N1) virus has the potential to increase the #mammalian #pathogenicity

Abstract Influenza, a highly contagious respiratory infectious disease caused by an influenza virus , is a threat to public health worldwide . Avian influenza viruses (AIVs) have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome. Here, we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models . In addition, we assessed the pathogenicity of AIVs in ferret models . Moreover, we compared the ability of viruses to replicate in mammalian cells , as well as the receptor-binding preferences of AIV isolates. Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation. Of the 24 AIV isolates tested, A/Mallard/South Korea/KNU2019-34/2019 (KNU19-34; H1N1) caused severe bodyweight loss and high mortality in mice . The virus rep...

#Mpox #mRNA-1769 #vaccine inhibits #orthopoxvirus #replication at intranasal, intrarectal, and cutaneous sites of inoculation

Abstract We previously reported that mice immunized twice with a lipid nanoparticle vaccine comprising four monkeypox viral mRNAs raised neutralizing antibodies and antigen-specific T cells and were protected against a lethal intranasal challenge with vaccinia virus (VACV). Here we demonstrated that the mRNA vaccine also protects mice against intranasal and intraperitoneal infections with monkeypox virus and bioluminescence imaging showed that vaccination greatly reduces or prevents VACV replication and spread from intranasal, rectal, and dermal inoculation sites. A single vaccination provided considerable protection that was enhanced by boosting for at least 4 months. Protection was related to the amount of mRNA inoculated, which correlated with neutralizing antibody levels . Furthermore, immunocompetent and immunodeficient mice lacking mature B and T cells that received serum from mRNA-immunized macaques before or after VACV challenge were protected. These findings provide insights i...