No abstract

Pre-existing immunity to influenza is dependent on a number of factors and can vary greatly within and across influenza subtypes. In this study, volunteers (aged 18–85 years) were vaccinated with split, inactivated FluzoneTM in four consecutive influenza seasons from 2013 to 2016. The impact of repeat vaccination on breadth and durability of functional antibodies was assessed for total IgG and IgA anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity against both influenza B lineages. Many subjects were able to maintain high seroprotective titers to the vaccine strains in subsequent years, which resulted in low vaccine-induced seroconversion rates. This was especially evident in younger subjects who typically had higher titers and maintained these titers into the following season. In contrast, the HAI titers in elderly subjects were generally lower and more likely to decline prior to the start of the next influenza season. Immunological recall or ‘back-boosting’ to antigenically related viruses was associated with seroconversion. Overall, influenza vaccination in both younger and older people elicited broadly reactive immune responses within a lineage, as well as cross-reactive immune responses between lineages. This study exemplified the impact that age and influenza exposure history have on determining an individual’s ability to respond to future influenza infections.

Influenza is a highly contagious viral respiratory disease that affects millions of people worldwide each year. Annual vaccination is recommended by the World Health Organization to reduce influenza severity and limit transmission through elicitation of antibodies targeting mainly the hemagglutinin glycoprotein of the influenza virus. Antibodies elicited by current seasonal influenza vaccines are predominantly strain-specific. However, continuous antigenic drift by circulating influenza viruses facilitates escape from pre-existing antibodies requiring frequent reformulation of the seasonal influenza vaccine. Traditionally, immunological responses to influenza vaccination have been largely focused on IgG antibodies, with almost complete disregard of other isotypes. In this report, young adults (18-34 years old) and elderly (65-85 years old) subjects were administered the split inactivated influenza vaccine for 3 consecutive seasons and their serological IgA and IgG responses were profiled. Moreover, correlation analysis showed a positive relationship between vaccine-induced IgA antibody titers and traditional immunological endpoints, exposing vaccine-induced IgA antibodies as an important novel immune correlate during influenza vaccination.

Influenza is a highly contagious viral respiratory disease that affects million of people worldwide each year. Annual vaccination is recommended by the World Health Organization with the goal of reducing influenza severity and limiting transmission through elicitation of antibodies targeting the hemagglutinin (HA) glycoprotein. The antibody response elicited by current seasonal influenza virus vaccines is predominantly strain-specific, but pre-existing influenza virus immunity can greatly impact the serological antibody response to vaccination. However, it remains unclear how B cell memory is shaped by recurrent annual vaccination over the course of multiple seasons, especially in high-risk elderly populations. Here, we systematically profiled the B cell response in young adult (18–34 year old) and elderly (65+ year old) vaccine recipients that received annual split inactivated influenza virus vaccination for 3 consecutive seasons. Specifically, the antibody serological and memory B-cell compartments were profiled for reactivity against current and historical influenza A virus strains. Moreover, multiparametric analysis and antibody landscape profiling revealed a transient increase in strain-specific antibodies in the elderly, but with an impaired recall response of pre-existing memory B-cells, plasmablast (PB) differentiation and long-lasting serological changes. This study thoroughly profiles and compares the immune response to recurrent influenza virus vaccination in young and elderly participants unveiling the pitfalls of current influenza virus vaccines in high-risk populations.

Influenza is a highly contagious viral respiratory disease with more than 200 thousand cases reported in the US last season (2017/18). Annual vaccination is recommended by the World Health Organization with the goal to reduce influenza severity and limit transmission. However, currently available split inactivated influenza vaccines can only elicit protection up to ~60% in well-matched-strain years. Furthermore, vaccine effectiveness frequently varies between different influenza subtypes within a single influenza season for unclear reasons. Immunological imprinting from early-life influenza infection can prominently shape the immune response to subsequent infections. Here, the impact of pre-existing B-cell memory in the response to quadrivalent influenza vaccine was assessed. Blood samples were collected from healthy subjects (18 to 85 years old) prior to vaccination and 21–28 days after vaccination with quadrivalent influenza vaccine. Samples were assessed for changes in serological antibodies to the hemagglutinin protein (HA) by ELISA and by hemagglutination-inhibition (HAI) assays against the four strains in the vaccine. The number of antigen specific memory B-cells (Bmem) were quantified by flow cytometry and the polyclonal Bmemresponse was assessed against the HA of the four vaccine strains. Influenza vaccination greatly induces the HA-specific Bmem-cell pool and, despite no differences in antigenicity between the four vaccine components, most individuals are biased towards one of the influenza A or Influenza B vaccine strains. Overall, this study unveils a new mechanism behind the differences in vaccine effectiveness against different influenza subtypes.