Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys

Joshua M. Dinapoli, Baibaswata Nayak, Lijuan Yang, Brad W. Finneyfrock, Anthony Cook, Hanne Andersen, Fernando Torres-Velez, Brian R. Murphy, Siba K. Samal, Peter L. Collins, Alexander Bukreyev

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Abstract

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 we 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-pathogenicity strain of influenza virus [HA(RV)], in order to address concerns of enhanced vector replication or genetic exchange, or HPAIV neuraminidase (NA). The three vaccine viruses [NDV/HA, NDV/HA(RV), and 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 administration. 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 2 × 107 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.

Original languageEnglish (US)
Pages (from-to)1489-1503
Number of pages15
JournalJournal of Virology
Volume84
Issue number3
DOIs
StatePublished - Feb 2010
Externally publishedYes

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Newcastle disease virus
Influenza in Birds
sialidase
Hemagglutinins
Neuraminidase
hemagglutinins
Orthomyxoviridae
Influenza A virus
Haplorhini
monkeys
Vaccines
vaccines
Viruses
viruses
Proteins
proteins
Primates
aerosols
Aerosols
Avulavirus

ASJC Scopus subject areas

  • Immunology
  • Virology

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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, Joshua M.; Nayak, Baibaswata; Yang, Lijuan; Finneyfrock, Brad W.; Cook, Anthony; Andersen, Hanne; Torres-Velez, Fernando; Murphy, Brian R.; Samal, Siba K.; Collins, Peter L.; Bukreyev, Alexander.

In: Journal of Virology, Vol. 84, No. 3, 02.2010, p. 1489-1503.

Research output: Contribution to journalArticle

Dinapoli, Joshua M. ; Nayak, Baibaswata ; Yang, Lijuan ; Finneyfrock, Brad W. ; Cook, Anthony ; Andersen, Hanne ; Torres-Velez, Fernando ; Murphy, Brian R. ; Samal, Siba K. ; Collins, Peter L. ; Bukreyev, Alexander. / Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys. In: Journal of Virology. 2010 ; Vol. 84, No. 3. pp. 1489-1503.
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abstract = "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 we 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-pathogenicity strain of influenza virus [HA(RV)], in order to address concerns of enhanced vector replication or genetic exchange, or HPAIV neuraminidase (NA). The three vaccine viruses [NDV/HA, NDV/HA(RV), and 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 administration. 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 2 × 107 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.",
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AU - Nayak, Baibaswata

AU - Yang, Lijuan

AU - Finneyfrock, Brad W.

AU - Cook, Anthony

AU - Andersen, Hanne

AU - Torres-Velez, Fernando

AU - Murphy, Brian R.

AU - Samal, Siba K.

AU - Collins, Peter L.

AU - Bukreyev, Alexander

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