Abstract
Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies that provide with sterilizing immunity. However, influenza vaccination often confers protection from disease but not from infection. The impact of infection-permissive vaccination on the immune response elicited by subsequent influenza virus infection is not well-understood. Here, we investigated to what extent infection-permissive immunity, in contrast to virus-neutralizing immunity, provided by a trivalent inactivated virus vaccine (TIV) modulates disease and virus-induced host immune responses after sublethal vaccine-matching H1N1 infection in a mouse model. More than one TIV vaccination was needed to induce a serum HI titer and provide sterilizing immunity upon homologous virus infection. However, single TIV administration provided infection-permissive immunity, characterized by lower viral lung titers and faster recovery. Despite the presence of replicating virus, single TIV vaccination prevented induction of pro-inflammatory cyto- and chemokines, alveolar macrophage depletion as well as the establishment of lung-resident B and T cells after infection. To investigate virus infection-induced cross-protective heterosubtypic immune responses in vaccinated and unvaccinated animals, mice were re-infected with a lethal dose of H3N2 virus 4 weeks after H1N1 infection. Single TIV vaccination did not prevent H1N1 virus infection-induced heterosubtypic cross-protection, but shifted the mechanism of cross-protection from the cellular to the humoral branch of the immune system. These results suggest that suboptimal vaccination with conventional influenza vaccines may still positively modulate disease outcome after influenza virus infection, while promoting humoral heterosubtypic immunity after virus infection.
Highlights
Over the course of a lifetime, humans are repeatedly exposed to influenza virus by natural infection or vaccination
We investigated the effect of pre-existing immunity on virus-host immune responses during H1N1 influenza A virus infection, and how this correlates with protection during re-infection with an influenza virus of a different subtype
Pre-existing immunity was provided by trivalent inactivated influenza virus vaccine (TIV) vaccination that was titrated to provide protection in the absence of complete virus neutralization, as was evident from the replicating virus observed in the lungs of TIV NC99 mice
Summary
Over the course of a lifetime, humans are repeatedly exposed to influenza virus by natural infection or vaccination. Due to its error prone replication complex, influenza virus acquires mutations (antigenic drift) that allow it to evade pre-existing host immune responses. The virus is responsible for causing annually recurrent respiratory disease worldwide [1]. Influenza virus can exchange gene segments (antigenic shift), generating each 10–50 years novel pandemic influenza viruses that the human population is naïve to. Vaccines are the best method of protection, but are strain specific. Annual re-formulation and re-administration of the vaccine is necessary. The repeated infection and vaccination people undergo throughout life leads to the buildup of influenza-specific immunity in individuals
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