The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations

Ferrucci, 1997, Hospital diagnoses, medicare charges, and nursing home admissions in the year when older persons become severely disabled, JAMA, 277, 728, 10.1001/jama.1997.03540330050034 Goodwin, 2006, Antibody response to influenza vaccination in the elderly: a quantitative review, Vaccine, 24, 1159, 10.1016/j.vaccine.2005.08.105 McElhaney, 2011, Influenza vaccine responses in older adults, Ageing Res Rev, 10, 379, 10.1016/j.arr.2010.10.008 McElhaney, 2009, Immunosenescence: what does it mean to health outcomes in older adults, Curr Opin Immunol, 21, 418, 10.1016/j.coi.2009.05.023 Simonsen, 2007, Mortality benefits of influenza vaccination in elderly people: an ongoing controversy, Lancet Infect Dis, 7, 658, 10.1016/S1473-3099(07)70236-0 Targonski, 2007, Immunosenescence: role and measurement in influenza vaccine response among the elderly, Vaccine, 25, 3066, 10.1016/j.vaccine.2007.01.025 Gross, 1995, The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature, Ann Intern Med, 123, 518, 10.7326/0003-4819-123-7-199510010-00008 Simonsen, 1998, Pandemic versus epidemic influenza mortality: a pattern of changing age distribution, J Infect Dis, 178, 53, 10.1086/515616 Frasca, 2013, Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011–2012 influenza vaccine season, Immun Ageing, 10, 14, 10.1186/1742-4933-10-14 Frasca, 2012, Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine, Int Immunol, 24, 175, 10.1093/intimm/dxr123 Khurana, 2012, AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans, PLoS Pathog, 8, e1002920, 10.1371/journal.ppat.1002920 Khurana, 2012, Immune response following H1N1pdm09 vaccination: differences in antibody repertoire and avidity in young adults and elderly populations stratified by age and gender, J Infect Dis, 205, 610, 10.1093/infdis/jir791 Sasaki, 2011, Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies, J Clin Investig, 121, 3109, 10.1172/JCI57834 Verma, 2012, Influenza virus H1N1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (HA1 Domain) in the elderly than in young adults and children, J Virol, 86, 5515, 10.1128/JVI.07085-11 Bernstein, 1999, Immune response to influenza vaccination in a large healthy elderly population, Vaccine, 17, 82, 10.1016/S0264-410X(98)00117-0 Frasca, 2010, Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans, Vaccine, 28, 8077, 10.1016/j.vaccine.2010.10.023 McElhaney, 2013, AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial, Lancet Infect Dis, 13, 485, 10.1016/S1473-3099(13)70046-X Murasko, 2002, Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly, Exp Gerontol, 37, 427, 10.1016/S0531-5565(01)00210-8 van Essen, 2014, Influenza symptoms and their impact on elderly adults: randomised trial of AS03-adjuvanted or non-adjuvanted inactivated trivalent seasonal influenza vaccines, Influenza Other Respir Viruses, 8, 452, 10.1111/irv.12245 Amanna, 2007, Duration of humoral immunity to common viral and vaccine antigens, N Engl J Med, 357, 1903, 10.1056/NEJMoa066092 Frasca, 2013, Young and elderly patients with type 2 diabetes have optimal B cell responses to the seasonal influenza vaccine, Vaccine, 31, 3603, 10.1016/j.vaccine.2013.05.003 Sasaki, 2008, Influence of prior influenza vaccination on antibody and B-cell responses, PLoS ONE, 3, e2975, 10.1371/journal.pone.0002975 Pritz, 2015, Plasma cell numbers decrease in bone marrow of old patients, Eur J Immunol, 45, 738, 10.1002/eji.201444878 Kaml, 2006, Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers, Vaccine, 24, 6808, 10.1016/j.vaccine.2006.06.037 Frasca, 2014, High TNF-alpha levels in resting B cells negatively correlate with their response, Exp Gerontol, 54, 116, 10.1016/j.exger.2014.01.004 Frasca, 2015, Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine, Vaccine, 33, 1433, 10.1016/j.vaccine.2015.01.071 Frasca, 2015, Micro-RNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals, J Immunol, 195, 2134, 10.4049/jimmunol.1500520 Frasca, 2016, Obesity decreases B cell responses in young and elderly individuals, Obesity, 24, 615, 10.1002/oby.21383 Faenzi, 2012, One dose of an MF59-adjuvanted pandemic A/H1N1 vaccine recruits pre-existing immune memory and induces the rapid rise of neutralizing antibodies, Vaccine, 30, 4086, 10.1016/j.vaccine.2012.04.020 Wrammert, 2008, Rapid cloning of high-affinity human monoclonal antibodies against influenza virus, Nature, 453, 667, 10.1038/nature06890 Cox, 1994, An early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination, Vaccine, 12, 993, 10.1016/0264-410X(94)90334-4 Frasca, 2008, Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells, J Immunol, 180, 5283, 10.4049/jimmunol.180.8.5283 Goenka, 2014, Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics, Exp Gerontol, 54, 109, 10.1016/j.exger.2013.12.013 Skowronski, 2008, Rapid decline of influenza vaccine-induced antibody in the elderly: is it real, or is it relevant, J Infect Dis, 197, 490, 10.1086/524146 Shaffer, 2002, Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program, Immunity, 17, 51, 10.1016/S1074-7613(02)00335-7 Andrews, 2015, High preexisting serological antibody levels correlate with diversification of the influenza vaccine response, J Virol, 89, 3308, 10.1128/JVI.02871-14 Pyhala, 1994, HI antibody kinetics in adult volunteers immunized repeatedly with inactivated trivalent influenza vaccine in 1990–1992, Vaccine, 12, 947, 10.1016/0264-410X(94)90039-6 de Bruijn, 1999, Quality and quantity of the humoral immune response in healthy elderly and young subjects after annually repeated influenza vaccination, J Infect Dis, 179, 31, 10.1086/314540 Rinaldi, 2014, Antibody but not memory B-cell responses are tuned-down in vertically HIV-1 infected children and young individuals being vaccinated yearly against influenza, Vaccine, 32, 657, 10.1016/j.vaccine.2013.12.008