Giuseppe
Emeritus
J Virol. 2009 Nov 18. [Epub ahead of print]
Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys.
Dinapoli JM, Nayak B, Yang L, Finneyfrock BW, Cook A, Andersen H, Torres-Velez F, Murphy BR, Samal SK, Collins PL, Bukreyev A. - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA; Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA; Bioqual, Inc., Rockville, Maryland 20850, USA; Infectious Diseases Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
H5N1 highly pathogenic avian influenza virus (HPAIV) causes periodic outbreaks in humans, resulting in severe infections with a high (60%) incidence of mortality. The circulating strains have low human-to-human transmissibility; however, widespread concerns exist that enhanced transmission due to mutations could lead to a global pandemic. We previously engineered Newcastle disease virus (NDV) - an avian paramyxovirus - as a vector to express the HPAIV hemagglutinin (HA) protein, and showed that this vaccine (NDV/HA) induced a high level of HPAIV-specific mucosal and serum antibodies in primates when administered through the respiratory tract. Here, we developed additional NDV-vectored vaccines expressing either HPAIV HA in which the polybasic cleavage site was replaced with that from a low-pathogenic strain of influenza [HA(RV)], to address concerns of enhanced vector replication or genetic exchange, or the HPAIV neuraminidase (NA). The three vaccine viruses [NDV/HA, NDV/HA(RV), NDV/NA] were administered separately to groups of African green monkeys by the intranasal/intratracheal route. An additional group of animals received NDV/HA by aerosol. Each of the vaccine constructs was highly restricted for replication, with only low levels of virus shedding detected in respiratory secretions. All groups developed high levels of neutralizing antibodies against homologous and heterologous strains of HPAIV, and were protected against challenge with 2x10(7) plaque forming units (PFU) of homologous HPAIV. Thus, needle-free, highly-attenuated NDV-vectored vaccines expressing either HPAIV HA, HA(RV), or NA have been developed and demonstrated to be individually immunogenic and protective in a primate model of HPAIV infection. The finding that HA(RV) was protective indicates that it would be preferred for inclusion in a vaccine. The study also identified NA as an independent protective HPAIV antigen in primates. Furthermore, we demonstrated the feasibility of aerosol delivery of NDV-vectored vaccines.
PMID: 19923177 [PubMed - as supplied by publisher]
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Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys.
Dinapoli JM, Nayak B, Yang L, Finneyfrock BW, Cook A, Andersen H, Torres-Velez F, Murphy BR, Samal SK, Collins PL, Bukreyev A. - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA; Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland 20742, USA; Bioqual, Inc., Rockville, Maryland 20850, USA; Infectious Diseases Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
H5N1 highly pathogenic avian influenza virus (HPAIV) causes periodic outbreaks in humans, resulting in severe infections with a high (60%) incidence of mortality. The circulating strains have low human-to-human transmissibility; however, widespread concerns exist that enhanced transmission due to mutations could lead to a global pandemic. We previously engineered Newcastle disease virus (NDV) - an avian paramyxovirus - as a vector to express the HPAIV hemagglutinin (HA) protein, and showed that this vaccine (NDV/HA) induced a high level of HPAIV-specific mucosal and serum antibodies in primates when administered through the respiratory tract. Here, we developed additional NDV-vectored vaccines expressing either HPAIV HA in which the polybasic cleavage site was replaced with that from a low-pathogenic strain of influenza [HA(RV)], to address concerns of enhanced vector replication or genetic exchange, or the HPAIV neuraminidase (NA). The three vaccine viruses [NDV/HA, NDV/HA(RV), NDV/NA] were administered separately to groups of African green monkeys by the intranasal/intratracheal route. An additional group of animals received NDV/HA by aerosol. Each of the vaccine constructs was highly restricted for replication, with only low levels of virus shedding detected in respiratory secretions. All groups developed high levels of neutralizing antibodies against homologous and heterologous strains of HPAIV, and were protected against challenge with 2x10(7) plaque forming units (PFU) of homologous HPAIV. Thus, needle-free, highly-attenuated NDV-vectored vaccines expressing either HPAIV HA, HA(RV), or NA have been developed and demonstrated to be individually immunogenic and protective in a primate model of HPAIV infection. The finding that HA(RV) was protective indicates that it would be preferred for inclusion in a vaccine. The study also identified NA as an independent protective HPAIV antigen in primates. Furthermore, we demonstrated the feasibility of aerosol delivery of NDV-vectored vaccines.
PMID: 19923177 [PubMed - as supplied by publisher]
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