Profiling of humoral response to influenza A(H1N1)pdm09 infection and vaccination measured by a protein microarray in persons with and without history of seasonal vaccination

Abstract

Background: The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood.

Methods: We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination.

Results: We showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens.

Conclusions: Seasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.

Figure 1. HI versus PA for influenza A(H1N1)pdm09 in the natural infection-group and in the vaccination group. A.

GMTs of influenza A(H1N1)pdm09 for HI versus PA in the natural infection-group, with and without prior seasonal vaccination at time point 0 represents baseline, time point 1 represents 10 days after day of onset of influenza symptoms and time point 2 represents 30 days after day of onset of influenza symptoms. B. GMTs of influenza A(H1N1)pdm09 for HI versus PA in the vaccination group, with and without prior seasonal influenza vaccination at time point 0 represents baseline, time point 1 represents 3 weeks after the first vaccination and before the second vaccination and time point 2 represents 5 weeks after the second vaccination. Y axis denotes average GMT (adjusted for gender and age).

Figure 2. Geometric mean titers (GMT) at time point 1 and 2 of the natural infection-group and in the vaccination group with and without former seasonal influenza vaccination. A.

GMTs for the various influenza HA1 antigens in patients infected with pandemic influenza H1 2009, with and without a history of seasonal vaccination at time point 1 (10 days after day of onset of influenza symptoms) and time point 2 (30 days after day of onset of influenza symptoms). B. GMTs for the various influenza HA1 antigens in subjects vaccinated with inactivated MF-59 adjuvated pandemic Influenza A virus (H1N1) 2009, with and without a history of seasonal influenza vaccination at time point 0, 1 (3 weeks after the first vaccination and before the second vaccination) and time point 2 (5 weeks after the second vaccination). Y axis denotes average GMT (adjusted for gender and age).