Booster vaccination against tetanus and diphtheria: insufficient protection against diphtheria in young and elderly adults

Abstract

We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5 year intervals. In the present study we have immunized a group of young adults against tetanus and diphtheria to compare the pre- and 28 days post-vaccination immune responses in the young group with results of the same vaccination performed in an elderly group of a previous study. We also studied protection in both groups 5 years after vaccination. We compared antibody titers at all three time points and also analyzed the T cell responses in both age groups 5 years after vaccination.Before vaccination 9 % of the elderly persons were not protected against tetanus, and 48 % did not have protection against diphtheria. In the young group all participants were protected against tetanus, but 52 % were also unprotected against diphtheria before vaccination. 28 days after vaccination 100 % of all participants had protective antibody concentrations against tetanus and only a small percentage in each age group (<10 %) was unprotected against diphtheria. 5 years later, 100 % of both cohorts were still protected against tetanus, but 24 % of the young and 54 % of the elderly group were unprotected against diphtheria. Antibody concentrations against diphtheria measured by ELISA correlated well with their neutralizing capacity. T cell responses to tetanus and diphtheria did not differ between young and old persons. We conclude that booster vaccinations against tetanus and diphtheria according to present recommendations provide long-lasting protection only against tetanus, but not against diphtheria, independently of age. In elderly persons, the level of protection is even lower, probably due to intrinsic age-related changes within the immune system and/or insufficient vaccination earlier in life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-016-0081-0) contains supplementary material, which is available to authorized users.

From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by “inflamm-ageing”

“…It is known that inflammation is important for survival in the earlier stage of life to fight infections and for the tissues repair, but it can have adverse and detrimental effects on aged individuals ("antagonistic pleiotropic theory", Goto, 2008). Indeed, as discussed, elderly are characterized by a subclinical chronic inflammatory condition termed "inflamm-ageing", which contributes to the development of a variety of age-associated diseases such as metabolic, cardiovascular, autoimmune and neurodegenerative diseases and cancer (Bucci et al, 2014;Fulop et al, 2016;Grasse et al, 2016;Grubeck-Loebenstein et al, 2009;Johnson and Cambier, 2004;Rubtsova et al, 2015;Salvioli et al, 2013). The condition of inflamm-ageing provides a continuous mild antigenic challenge that leads to a progressive stimulation, or depletion, of the immune system cells and to filling of the immunological space by activated/exhausted lymphocytes with altered functions (Bulati et al, 2011(Bulati et al, , 2014Fulop et al, 2016;Larbi and Fulop, 2014;Naradikian et al, 2016;Pawelec, 2014a,b;Pinti et al, 2016;Rubtsova et al, 2015).…”

“…Inflamm-ageing is, therefore, directly linked to the immune system (Salvioli et al, 2013). Indeed, it has been widely demonstrated a strong association between changes in immune functions and longevity, that indicates as the deterioration of the immune function, termed "immunosenescence", could be the cause of the increased susceptibility to infectious diseases, cancer, dementia, cardiovascular diseases and autoimmunity, and a decrease response to vaccination which characterize elderly people (Bucci et al, 2014;Fulop et al, 2016;Grasse et al, 2016;Salvioli et al, 2013). The age-associated deregulation of the immune system is due to changes in both innate and acquired immunity, strictly associated with a systemic chronic inflammation (Salvioli et al, 2013), as demonstrated in several longitudinal studies in which it was examined the relationship occurring between immune parameters and survival of very old subjects (Wikby et al, 2005).…”

Influence of immune aging on vaccine responses

“…Here, both vaccine antigens induce robust effector responses, reaching similar antibody titers in both young and old adults. 87,88 However, 5 years after vaccination, more than half (54%) of older adults have lost protective levels of diphtheria-specific antibodies, versus a quarter (24%) of young adults. 87 Conversely, all individuals maintained high protective levels of tetanus-specific antibodies.…”

Vaccines for the elderly: current use and future challenges

“…We could show that approximately 10% of a healthy elderly cohort recruited in Austria did not develop protective antibodies against diphtheria after a single booster shot and that almost half of the participants did not have antibodies above protective levels 5 years later. A second booster shot at this time point did again not provide long-term protection [ 48 , 49 ]. This could be due to insufficient priming earlier in life, inadequate boosters throughout adulthood or age-related defects of the immune system.…”