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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 μg 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. [ABSTRACT FROM AUTHOR]

The rapid spread of avian influenza (H5N1) and its transmission to humans has raised the possibility of an imminent pandemic and concerns over the ability of standard influenza vaccine production methods to 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, produced at a variety of manufacturing scales, were demonstrated to be highly immunogenic in animal models without the need for adjuvant. The vaccines induce cross-neutralising antibodies and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from other clades. 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. [ABSTRACT FROM AUTHOR]

Abstract: Recently the urgency of developing a pandemic influenza vaccine has lead to the re-evaluation of the use of whole virus vaccine. We have compared the humoral immune response and the protective efficacy of whole and split influenza virus vaccines in mice. Whole virus vaccine was more immunogenic particularly after the first dose of vaccine, generally eliciting higher numbers of systemic antibody secreting cells and an earlier and higher neutralising antibody response. Immunisation with one dose of whole virus vaccine more effectively reduced viral shedding upon non-lethal homologous viral challenge, but two doses of split virus vaccine was most effective at limiting viral replication and this was correlated with high influenza specific serum IgG concentrations. The two vaccine formulations induced different T helper profiles particularly after one dose of vaccine; split virus vaccine induced a type 2 bias response, whereas whole virus vaccine elicited a dominant type 1 response. [Copyright &y& Elsevier]