2009•Influenza and Other Respiratory VirusesOpen access

A pilot study of the immune response to whole inactivated avian influenza H7N1 virus vaccine in mice

Arnt‐Ove Hovden, Karl Albert Brokstad, Diane Major, John Martin Wood, Lars Reinhardt Haaheim, Rebecca Jane Cox

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Abstract

BACKGROUND: Highly pathogenic avian influenza (HPAI) outbreaks in domestic poultry bring humans into close contact with new influenza subtypes and represent a threat to human health. In 1999, an HPAI outbreak of H7N1 virus occurred in domestic poultry in Italy, and a wild-type virus isolate from this outbreak was chosen as a pandemic vaccine candidate. OBJECTIVES: We conducted a pilot study to investigate the kinetics of the humoral immune response induced after immunisation with an egg grown whole inactivated H7N1 virus vaccine in BALB/c mice. METHODS: Mice were vaccinated with one or two doses of H7N1 vaccine (15 microg total protein) to investigate the influenza specific antibody secreting cell (IS-ASC) and serum antibody responses. RESULTS: After the first dose of vaccine, only IgM IS-ASC were detected in the spleen and bone marrow, whereas IgG, IgA and IgM IS-ASC were found after the second dose. Low antibody titres were detected after the first immunisation, whilst the second dose of vaccine significantly boosted the HI (range 128-512), neutralising and IgG antibody titres. The IgG subclass response was dominated by IgG2a indicating a dominant Th1 response after the first vaccination, whereas a more mixed Th1/Th2 profile was observed after the second dose. CONCLUSIONS: This pilot study shows the value of using a number of immunological methods to evaluate the quality of the immune response to potential pandemic candidate vaccines.

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BACKGROUND: Highly pathogenic avian influenza (HPAI) outbreaks in domestic poultry bring humans into close contact with new influenza subtypes and represent a threat to human health. In 1999, an HPAI outbreak of H7N1 virus occurred in domestic poultry in Italy, and a wild-type virus isolate from this outbreak was chosen as a pandemic vaccine candidate. OBJECTIVES: We conducted a pilot study to investigate the kinetics of the humoral immune response induced after immunisation with an egg grown whole inactivated H7N1 virus vaccine in BALB/c mice. METHODS: Mice were vaccinated with one or two doses of H7N1 vaccine (15 microg total protein) to investigate the influenza specific antibody secreting cell (IS-ASC) and serum antibody responses. RESULTS: After the first dose of vaccine, only IgM IS-ASC were detected in the spleen and bone marrow, whereas IgG, IgA and IgM IS-ASC were found after the second dose. Low antibody titres were detected after the first immunisation, whilst the second dose of vaccine significantly boosted the HI (range 128-512), neutralising and IgG antibody titres. The IgG subclass response was dominated by IgG2a indicating a dominant Th1 response after the first vaccination, whereas a more mixed Th1/Th2 profile was observed after the second dose. CONCLUSIONS: This pilot study shows the value of using a number of immunological methods to evaluate the quality of the immune response to potential pandemic candidate vaccines.

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Available abstract

BACKGROUND: Highly pathogenic avian influenza (HPAI) outbreaks in domestic poultry bring humans into close contact with new influenza subtypes and represent a threat to human health. In 1999, an HPAI outbreak of H7N1 virus occurred in domestic poultry in Italy, and a wild-type virus isolate from this outbreak was chosen as a pandemic vaccine candidate. OBJECTIVES: We conducted a pilot study to investigate the kinetics of the humoral immune response induced after immunisation with an egg grown whole inactivated H7N1 virus vaccine in BALB/c mice. METHODS: Mice were vaccinated with one or two doses of H7N1 vaccine (15 microg total protein) to investigate the influenza specific antibody secreting cell (IS-ASC) and serum antibody responses. RESULTS: After the first dose of vaccine, only IgM IS-ASC were detected in the spleen and bone marrow, whereas IgG, IgA and IgM IS-ASC were found after the second dose. Low antibody titres were detected after the first immunisation, whilst the second dose of vaccine significantly boosted the HI (range 128-512), neutralising and IgG antibody titres. The IgG subclass response was dominated by IgG2a indicating a dominant Th1 response after the first vaccination, whereas a more mixed Th1/Th2 profile was observed after the second dose. CONCLUSIONS: This pilot study shows the value of using a number of immunological methods to evaluate the quality of the immune response to potential pandemic candidate vaccines.

Key concepts: Virology, Immune system, Vaccination, Virus, Influenza A virus subtype H5N1, Inactivated vaccine, Biology, Antibody

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