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

BackgroundThe influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood.MethodsWe 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.ResultsWe 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.ConclusionsSeasonal 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.

Heterosubtypic cross-reactivity of HA1 antibodies to influenza A, with emphasis on nonhuman subtypes (H5N1, H7N7, H9N2)

“…As with the hemagglutination inhibition assay, measurements based on this test are not necessarily protective. It is known, however, that responses in the microarray correlate well with corresponding HI titers [41][42][43]. In our data, we found a strong correlation between microarray titers and (standardized) HI titers when using A/2009 (H1N1) antigen, with a (standardized) HI titer of 40 translating roughly to a microarray titer of 80 [43].…”

“…We draw an age stratified random subset of these surveys (167 pre-pandemic samples and 190 post-pandemic samples), oversampling sera with high A/2009 (H1N1) HI titers [43]. Persons who had received pandemic vaccinations were not eligible for selection because of the interference of vaccination with the microarray test results [41]. Full details on the antibody protein array have been described earlier [41,42].…”

“…To assess the extent of cross-reactivity of antibody responses to historic influenza viruses in the human population we analyze cross-sectional serological survey data from the Netherlands obtained before and after the A/H1N1 pandemic of 2009 [7]. The samples had been tested by hemagglutination inhibition test using pandemic A/2009 (H1N1) virus as antigen, and by hemagglutinin subunit 1 (HA1) protein microarray using a suite of human H1N1, H2N2, and H3N2 viruses, and avian H5N1, H7N7 and H9N2 viruses [40][41][42]. Earlier analyses focused on A/1918 (H1N1) and A/2009 (H1N1) HA1 antigens, to investigate diagnostic characteristics of the new tests to distinguish persons infected during the pandemic of 2009 from those with preexisting immunity [43], and to estimate infection attack rates and population levels of preexisting immunity [8].…”

Structure of general-population antibody titer distributions to influenza A virus

“…The main difference between these models was the presence of the first small peak (titer range 19.7 to 45.0) which helped improve the BIC and minimized the overlap between the two highest titer components. Epidemiologically, this first peak represents seronegative individuals with very low titer values [38,39,48]. For H3N2, the results were clearer as the BIC selected three components as the best model for all sites ( Figure S8).…”

“…With a mixture model approach, we were able to identify the presence of multiple exposure groups in the population according to their titers. Our interpretation of these multiple exposure groupsaccording to titers measured for confirmed cases [48] and past measurements of the rate of antibody waning [49,50] -is that they represent recently infected individuals, historically (i.e. not recently)…”