Control of pandemic (H1N1) 2009 influenza virus infection of ferret lungs by non-adjuvant-containing pandemic and seasonal vaccines

The pandemic H1N1 2009 influenza virus caused relatively mild disease in most infected people but some suffered extensively from primary lung infection, many more than would have occurred with seasonal influenza infection. Early commercially available pandemic H1N1 vaccines did not contain adjuvant, as did many of the subsequent vaccines, and could not stop infection with the pandemic virus in vaccinated ferrets. Nevertheless, we showed that virus loads in the lungs were greatly diminished in ferrets vaccinated once with an unadjuvanted pandemic vaccine and challenged with 106 EID50 wildtype A/California/07/2009 (H1N1). In addition, a single inoculation with seasonal vaccine showed beneficial reduction in pandemic pulmonary virus loads in the absence of any detectable cross-reactive serological responses. Ferrets primed with either seasonal or pandemic vaccine and then boosted with pandemic vaccine also showed less extensive lung infection when challenged with a tenfold higher dose of pandemic virus. These results implicate non-classical protective mechanisms that prevent severe pulmonary disease but not viral shedding and imply that particular non-adjuvanted vaccines may have retained the ability to induce these responses.

► To protect against pandemic H1N1 influenza virus infection vaccines with adjuvants are needed.
► Yet protection against extensive lung infection was demonstrated by prior vaccination with unadjuvanted pandemic virus vaccine in the ferret model.
► Unadjuvanted seasonal vaccine could also provide cross-protection of the lung against extensive infection.
► Such non-classical responses may provide benefit from the lung disease that has led to severe outcomes in a cohort of people with pandemic H1N1 infection.