Breadth of Antibody Responses during Influenza Virus Infection and Vaccination

Inactivated vaccines are the best available way to induce effective antibodies against the Influenza virus, but the induced antibody response is narrow and subtype specific. The adaptive immune response to natural influenza virus infection is relatively broad and long lived and exhibits differing breadth and strength of antibody responses. Production of broadly reactive antibody in natural influenza virus infection depends on TFH cells and a GC reaction capable of expanding the responding B cell repertoire to recognize a common epitope. Initial natural infection with influenza virus leads to the breadth of the antibody response as an immunological ‘imprint’, leading to recall responses on secondary infection. Influenza viruses are a major public health problem, causing severe respiratory diseases. Vaccines offer the effective protective strategy against influenza virus infection. However, the systemic and adaptive immune responses to infection and vaccination are quite different. Inactivated vaccines are the best available countermeasure to induce effective antibodies against the emerged virus, but the response is narrow compared with potential breadth of virus infection. There is solid evidence to indicate that antibody responses to natural infection are relatively broad and exhibit quite different immunodominance patterns. Furthermore, T follicular helper cells (TFH) and germinal center (GC) responses play a central role in generating broad protective antibodies. In this review, we discuss recent advances on the contribution of TFH and GC responses to the breadth of antibody responses. Influenza viruses are a major public health problem, causing severe respiratory diseases. Vaccines offer the effective protective strategy against influenza virus infection. However, the systemic and adaptive immune responses to infection and vaccination are quite different. Inactivated vaccines are the best available countermeasure to induce effective antibodies against the emerged virus, but the response is narrow compared with potential breadth of virus infection. There is solid evidence to indicate that antibody responses to natural infection are relatively broad and exhibit quite different immunodominance patterns. Furthermore, T follicular helper cells (TFH) and germinal center (GC) responses play a central role in generating broad protective antibodies. In this review, we discuss recent advances on the contribution of TFH and GC responses to the breadth of antibody responses. directed against a swine-origin influenza A virus subtype H1N1 strain that was responsible for the 2009 pandemic infection. a seasonal H1N1 influenza A virus isolated in 1934 in Puerto Rico. Mouse-adapted strains of this have been widely used as a standard seasonal H1N1 strain. a small change in the antigenicity (e.g., of an influenza virus) that leads to immune evasion caused by random genetic variation. also referred to as antigenic shift; the process leading to an emerging new virus strain by the shuffling of viral genomes among gene segments of different virus strains. the tail region of an antibody that interacts with cell-surface receptors able to bind to its specific Fc receptor, which is required for complement- and antibody-dependent cell killing. sites where mature B cells proliferate, differentiate, and mutate Ig genes to increase antibody affinity (e.g., during virus infections). GCs are important sites responsible for the differentiation of long-lived plasma cells and memory B cells. contributes to the formation of antibodies binding to a specific antigen. This region comprises a framework region and a complementarity-determining region, forming the 3D structure fitting to an antigen’s shape. trimeric surface viral protein responsible for virus binding and entry into target cells. cross-protection against infection (e.g., with an influenza virus strain) other than the strain used for primary infection or vaccination. during an immune response, the preference for an antigen or epitope that is selectively targeted by the immune system relative to other antigens or epitopes. the first exposure to an influenza virus induces immunological memory and second exposures to antigenically different influenza virus strains induce a response to a common epitope. type of influenza vaccine uses in the form of a nasal spray. Cold-adapted mutant viruses have been designed to mimic the natural influenza virus infection. exist on the surface of the envelope protein in influenza viruses. Neuraminidase cleaves the sialic acid of HA to release virus particles from virus-infected cells. germline-encoded host sensors that recognize typical molecules in pathogens and play a role in the innate immune system. These receptors include transmembrane receptors such as TLRs and RIG-I. variation of an immunoglobulin repertoire (e.g., recognizing HA antigen, which is largely determined by selection with HA antigen). pattern recognition receptor that recognizes the RNA of an invading virus in the cytosol, inducing type I IFN responses. introduced in BCR genes during the development of memory B cells and plasmablasts, resulting in clonal selection and a high-affinity B cell repertoire. require the presence of T cell help to stimulate B cells to secrete antibody. this helper T cell dominantly localizes to B cell follicles and provides growth and differentiation signals to B cells. TFH cells express chemokine receptor CXCR5, which is required for entry into GCs, where humoral responses are regulated. pattern recognition transmembrane receptors that recognize structurally conserved molecules derived from microbes, such as lipopolysaccharide.