Abstract
Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological “non-responder type.” Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite administration at relatively short intervals. Sufficient antigen-specific B cell memory B generated by adequate priming and consecutive booster vaccinations and/or exposure is a prerequisite for long-term protection.Trial RegistrationEU Clinical Trials Register (EU-CTR); EudraCT number 2009-011742-26; www.clinicaltrialsregister.eu/ctr-search/trial/2009-011742-26/AT
Highlights
Between 1990 and 2010, the percentage of persons aged 65 years or over has risen from 13.9% to 17.4% in the European population (EU-27) and is estimated to reach 30% by 2060(European Commission, Demography Report 2010. http:// ec.europa.eu/eurostat)
Over the 5-year interval until the second vaccination antibody concentrations dropped under the protective limit in 10% of the participants and again all vaccinees developed antibody concentrations above 0.1IU/ml four weeks after the second vaccination
We investigated the level of protection against tetanus and diphtheria in the elderly population and analyzed the immune response to tetanus and diphtheria following two doses of vaccine applied at a 5-years interval
Summary
Between 1990 and 2010, the percentage of persons aged 65 years or over has risen from 13.9% to 17.4% in the European population (EU-27) and is estimated to reach 30% by 2060(European Commission, Demography Report 2010. http:// ec.europa.eu/eurostat). In a study conducted in France adults under the age of 30 years were shown to have received on average 7.1 (95%CI 6.9-7.2) doses of tetanus vaccine, which corresponds well with recommendations of 5 doses during childhood/adolescence and 10-year booster intervals in many countries. Similar data have been obtained for the usage of diphtheria vaccine in persons up to 60 years of age in France with slightly lower numbers of vaccines doses during life-time compared to young adults [6]. The goal of this study was to investigate the level of protection against tetanus and diphtheria in the elderly population and to analyze the immune response to tetanus and diphtheria following two doses of vaccine applied at a 5-years interval. A cohort of 252 persons aged 60 years or older received a booster vaccination against tetanus, diphtheria, pertussis and polio. We demonstrate that the chosen immunization strategy does not lead to long lasting immunity in many elderly persons due to a too small memory B cell/plasma cell pool
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