Abstract
Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the effect of suboptimal vaccination on the outcome of post-influenza bacterial superinfection. Methods: We established a mouse vaccination model that allows control of disease severity after influenza virus infection despite inefficient induction of virus-neutralizing antibody titers by vaccination. We investigated the effect of vaccination on virus-induced host immune responses and on the outcome of superinfection with Staphylococcus aureus. Results: Vaccination with trivalent inactivated virus vaccine (TIV) reduced morbidity after influenza A virus infection but did not prevent virus replication completely. Despite the poor induction of influenza-specific antibodies, TIV protected from mortality after bacterial superinfection. Vaccination limited loss of alveolar macrophages and reduced levels of infiltrating pulmonary monocytes after influenza virus infection. Interestingly, TIV vaccination resulted in enhanced levels of eosinophils after influenza virus infection and recruitment of neutrophils in both lungs and mediastinal lymph nodes after bacterial superinfection. Conclusion: These observations highlight the importance of disease modulation by influenza vaccination, even when suboptimal, and suggest that influenza vaccination is still beneficial to protect during bacterial superinfection in the absence of complete virus neutralization.
Highlights
Over the course of a lifetime, humans build up immunity to influenza viruses through natural infection and vaccination
We study the initial host immune response to infection with a sublethal dose of H1N1 influenza virus that is homologous to the H1N1 component of the trivalent inactivated virus vaccine (TIV)
enhanced luminescent immunosorbent assay (ELISA) titers in most samples tested (Figure 2A). When these serum samples were tested for their capacity to inhibit virus-mediated hemagglutination of red blood cells, a proxy assay for virus neutralization, only 33% of the samples from TIV-vaccinated mice tested had an hemagglutination inhibition (HI) titer at or above the detection limit (HI titer = 10) (Figure 2B)
Summary
Over the course of a lifetime, humans build up immunity to influenza viruses through natural infection and vaccination. The gold correlate of protection so far is an in vitro surrogate assay for virus neutralization based on the ability of serum antibodies to prevent virus from agglutinating red blood cells, which is called hemagglutination inhibition (HI). The presence of such antibodies is associated with a reduction in the likelihood of morbidity upon exposure to influenza virus [1]. It is very likely that, in the absence of virus-neutralizing antibodies, influenza virus-induced disease is modulated instead of prevented in the human host by non-neutralizing pre-existing immunity. We investigated the effect of vaccination on virus-induced host immune responses and on the outcome of superinfection with Staphylococcus aureus
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