Decreased vaccine protection of egg-based influenza vaccine in the elderly and nonhemagglutinin-focused immunity

Abstract

Severe influenza illness or death is a serious concern among the elderly population despite vaccination. To investigate how the adaptive immune response after vaccination varies with the patient's age, Jung et al., in a recent issue of the JCI, extensively analyzed the serum antibody response in different age groups after immunization with the egg-based influenza vaccine Fluzone. As expected, the immune response in young adults was dominated by antibodies targeting the influenza hemagglutinin (HA) protein. On the contrary, the serological repertoire of elderly donors was characterized by cross-reactive (CR) antibodies recognizing non-HA antigens. Surprisingly, a substantial fraction of these CR antibodies targeted sulfated glycans typical of egg-produced proteins, which does not provide protection against human influenza viruses. Overall, these findings are of great value in understanding suboptimal immunity after influenza vaccination and shaping future vaccine efforts that will achieve increased protection in the elderly.

Figure 1. Analysis pipeline of serological repertoires after vaccination with a split, inactivated egg-based influenza vaccine.

As a functional antibody response consists of BCRs expressed on the surface of B cells as well as of circulating antibodies in the blood, the analysis of both antibody repertoires is needed to study the humoral response generated after vaccination. Using BCR-Seq coupled with proteomic analysis of purified serum antibodies (Ig-Seq), Jung et al. found that, while the IgG clonotypic composition of young donors was predominantly specific for the H1 or H3 components of the influenza vaccine, the clonotypic composition in older adults was dominated by CR antibody clonotypes. The binding specificity of a set of expressed antibodies further evidenced that young individuals had an HA-focused response, whereas the response in older adults primarily targeted non-HA antigens, such as NP, M1, and egg-produced glycans. The bottom panel shows representative examples of the antibody specificity of serum antibodies according to Jung et al. (9).