Abstract
BackgroundLive attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360:1541, 2006). However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.Methodology and Principal FindingsPrimary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B) vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response.ConclusionThe findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness.
Highlights
Influenza pandemics can occur when new influenza subtypes capable of both infecting and spreading among humans emerge with a new hemagglutinin (HA) subtype to which there is little or no population immunity
The findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness
Several prototypic pandemic live attenuated influenza vaccine (LAIV) 6:2 reassortant viruses containing the H5N1 HA and NA gene segments have been produced on the backbone of six internal gene segments from the cold-adapted A/Ann Arbor/6/60 vaccine strain [9], the master donor virus (MDV-A) used to produce influenza A vaccine strains for the seasonal FluMistH influenza vaccines (MedImmune)
Summary
Influenza pandemics can occur when new influenza subtypes capable of both infecting and spreading among humans emerge with a new hemagglutinin (HA) subtype (antigenic shift) to which there is little or no population immunity. Several prototypic pandemic LAIV (pLAIV) 6:2 reassortant viruses containing the H5N1 HA and NA gene segments have been produced on the backbone of six internal gene segments from the cold-adapted (ca) A/Ann Arbor/6/60 vaccine strain [9], the master donor virus (MDV-A) used to produce influenza A vaccine strains for the seasonal FluMistH influenza vaccines (MedImmune). These candidate H5N1 vaccine strains, A/HK/491/97 (HK97 ca), A/HK/213/03 (HK03 ca), and A/VN/1203/04 (VN04 ca), were found to provide complete protection against lethal challenge with homologous and heterologous wild-type (wt) H5N1 viruses in mice and offered complete protection against pulmonary replication of wt H5N1 virus in ferrets [7]. The preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated
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