Pathogenesis of and Immunity to a New Influenza A (H5N1) Virus Isolated from Duck Meat

Lu, X. H.; Cho, D.; Hall, Henrietta; Rowe, Thomas; Mo, In-Pil; Sung, Haan Woo; Kim, W. J.; Kang, Chun; Cox, Nancy J.; Klimov, Alexander; Katz, Jacqueline M.

doi:10.1637/0005-2086-47.s3.1135

Cited by 60 publications

(101 citation statements)

References 29 publications

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“…In a previous report, an inactivated H5N3 alum-adjuvanted whole virus vaccine at high dosages (10μg) generated 100% protection of mice against a clade 1 H5N1 challenge [17]. Further, a single dose of a clade 1 H5N1 whole virus vaccine adjuvanted with incomplete Freund's adjuvant also fully protected mice against challenge with clade 1 virus at dosages of 7μg HA [32].…”

Section: Discussionmentioning

confidence: 88%

“…Subsequently, homologous T helper cell responses and potential heterologous crossstimulation responses were investigated using inbred Balb/c mice, widely used for influenza virus protection and virulence studies [17]. Animals were immunized twice (days 0 and 21) with either VN1203 or IN5/05 whole virus vaccines, a B/Jiangsu (B/JS) strain whole virus vaccine, rH5-HA antigen and saline.…”

Section: T Helper Cell Responses and Cross-stimulation In Micementioning

confidence: 99%

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Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced worldwide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.

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Section: Discussionmentioning

confidence: 88%

Section: T Helper Cell Responses and Cross-stimulation In Micementioning

confidence: 99%

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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show abstract

“…In contrast to the high pathogenicity and neurovirulence in mice observed with H5N1 viruses isolated from poultry and humans in Hong Kong in 1997 and from wild birds in Qinghai Lake in 2005 (Gao et al, 1999;Lu et al, 1999;Dybing et al, 2000;Liu et al, 2005;Zhou et al, 2006), both S and Y viruses were moderately pathogenic for mice, and no virus was detected in the brain from the challenged mice. Chen and colleagues demonstrated that duck H5N1 viruses isolated in 2001 and 2002 (intermediate or highly pathogenic) were more pathogenic in mice than those isolated in 1999 and 2000 (low pathogenicity) (Chen et al, 2004).…”

Section: Discussionmentioning

confidence: 89%

Characterization of duck H5N1 influenza viruses with differing pathogenicity in mallard (Anas platyrhynchos) ducks

Tang¹,

Wu²,

Peng³

et al. 2009

Avian Pathology

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A number of H5N1 influenza outbreaks have occurred in aquatic birds in Asia. As aquatic birds are the natural reservoir of influenza A viruses and do not usually show clinical disease upon infection, the repeated H5N1 outbreaks have highlighted the importance of continuous surveillance on H5N1 viruses in aquatic birds. In the present study we characterized the biological properties of four H5N1 avian influenza viruses, which had been isolated from ducks, in different animal models. In specific pathogen free (SPF) chickens, all four isolates were highly pathogenic. In SPF mice, the S and Y isolates were moderately pathogenic. However, in mallard ducks, two isolates had low pathogenicity, while the other two were highly pathogenic and caused lethal infection. A representative isolate with high pathogenicity in ducks caused systemic infection and replicated effectively in all 10 organs tested in challenged ducks, whereas a representative isolate with low pathogenicity in ducks was only detected in some organs in a few challenged ducks. Comparison of complete genomic sequences from the four isolates showed that the same amino acid residues that have been reported to be associated with virulence and host adaption/restriction of influenza viruses were present in the PB2, HA, NA, M and NS genes, while the amino acid residues at the HA cleavage site were diverse. From these results it appeared that the virulence of H5N1 avian influenza viruses was increased for ducks and that amino acid substitutions at the HA cleavage site might have contributed to the differing pathogenicity of these isolates in mallards. A procedure for the intravenous pathogenicity index test in a mallard model for assessing the virulence of H5/H7 subtype avian influenza viruses in waterfowl is described.

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“…Multiorgan spread and systemic virus replication are common features of pathogenic human and avian H5N1 (59,60) or avian/ equine H7N7 (60) infections of mice, but they are rare complications following inoculation with other human strains, even with the virulent 1918 H1N1 pandemic virus (61). In general terms, seasonal human influenza viruses remain confined to the respiratory tract in the mouse model, as the protease enzymes required to cleave viral HA0 are common in the lungs and trachea but not in other tissues.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Tate

Deng

Jones

et al. 2009

The Journal of Immunology

283

308

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The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.

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Pathogenesis of and Immunity to a New Influenza A (H5N1) Virus Isolated from Duck Meat

Cited by 60 publications

References 29 publications

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Characterization of duck H5N1 influenza viruses with differing pathogenicity in mallard (Anas platyrhynchos) ducks

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

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