Age Affects Quantity but Not Quality of Antibody Responses after Vaccination with an Inactivated Flavivirus Vaccine against Tick-Borne Encephalitis

Department of Virology, Medical University of Vienna, Vienna, Austria.
PLoS ONE (Impact Factor: 3.23). 03/2012; 7(3):e34145. DOI: 10.1371/journal.pone.0034145
Source: PubMed


The impairment of immune functions in the elderly (immunosenescence) results in post-vaccination antibody titers that are significantly lower than in young individuals. It is, however, a controversial question whether also the quality of antibodies declines with age. In this study, we have therefore investigated the age-dependence of functional characteristics of antibody responses induced by vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis (TBE). For this purpose, we quantified TBE virus-specific IgG and neutralizing antibody titers in post-vaccination sera from groups of young and elderly healthy adults and determined antibody avidities and NT/ELISA titer ratios (functional activity). In contrast to the quantitative impairment of antibody production in the elderly, we found no age-related differences in the avidity and functional activity of antibodies induced by vaccination, which also appeared to be independent of the age at primary immunization. There was no correlation between antibody avidity and NT/ELISA ratios suggesting that additional factors affect the quality of polyclonal responses, independent of age. Our work indicates that healthy elderly people are able to produce antibodies in response to vaccination with similar avidity and functional activity as young individuals, albeit at lower titers.

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    • ". Fold increase of TBE antibody concentration (ELISA) after catch-up vaccination in young and elderly adults. that the quality of antibodies in terms of avidity and functional activity (neutralization assay/ELISA ratio) is not different between young adults and the elderly [24]. Furthermore, it has been shown in our study as well as in other investigations that the fold increase of the anamnestic antibody response in the elderly is comparable to that of young adults [11] [25]. "
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    ABSTRACT: Intervals longer than recommended are frequently encountered between doses of tick borne encephalitis virus (TBE) vaccines in both residents of and travelers to endemic regions. In clinical practice the management of individuals with lapsed TBE vaccination schedules varies widely and has in common that the underlying immunological evidence is scarce. The aim of this study was to generate data reliable enough to derive practical recommendations on how to continue vaccination with FSME-IMMUN in subjects with an irregular TBE vaccination history. Antibody response to a single catch-up dose of FSME-IMMUN was assessed in 1115 adults (age ≥16 years) and 125 children (age 6-15 years) with irregular TBE vaccination histories. Subjects of all age groups developed a substantial increase in geometric mean antibody concentration after a single catch-up TBE vaccination which was consistently lower in subjects with only one previous TBE vaccination compared to subjects with two or more vaccinations. Overall, >94% of young adults and children, and >93% of elderly subjects with an irregular TBE vaccination history achieved antibody levels ≥25U/ml irrespective of the number of previous TBE vaccinations. We conclude that TBE vaccination of subjects with irregular vaccination histories should be continued as if the previous vaccinations had been administered in a regular manner, with the stage of the vaccination schedule being determined by the number of previous vaccinations. Although lapsed vaccination schedules may leave subjects temporarily with inadequate protection against TBE infection, adequate protection can quickly be re-established in >93% of the subjects by a single catch-up dose of FSME-IMMUN, irrespective of age, number of previous vaccinations, and time interval since the last vaccination.
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    • "Progeny virions are thought to assemble by budding into an intracellular membrane compartment, probably the endoplasmic reticulum, then transited through the host secretory pathway, and released at the cell surface [16]. Efforts to develop effective prophylactic approaches for several clinically important flaviviruses are underway [17]. The crucial role of the humoral immune response against Flavivirus infections is well established, as infection with one serotype provides life-long protective immunity to the homologous infecting serotype and cross-protection in the first few months against the other serotypes. "
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    ABSTRACT: More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminary in vitro and in vivo models of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.
    Full-text · Article · Aug 2013
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    • "Aging is associated with a decline in immune function, with an associated higher susceptibility to infections, incidence of cancer and autoimmunity [1-4]. Aging is also related to poor response to vaccination, including that to the influenza vaccine [5, 6]. At present, individuals can live up to 80-100 years, a much longer time than our ancestors typically managed. "
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    ABSTRACT: T-lymphocytes play a central role in the effector and regulatory mechanisms of the adaptive immune response. Upon exiting the thymus they begin to undergo a series of phenotypic and functional changes that continue throughout the lifetime and being most pronounced in the elderly. The reason postulated for this is that the dynamic processes of repeated interaction with cognate antigens lead to multiple division cycles involving a high degree of cell differentiation, senescence, restriction of the T-cell receptor (TCR) repertoire, and cell cycle arrest. This cell cycle arrest is associated with the loss of telomere sequences from the ends of chromosomes. Telomere length is reduced at each cell cycle, and critically short telomeres recruit components of the DNA repair machinery and trigger replicative senescence or apoptosis. Repetitively stimulated T-cells become refractory to telomerase induction, suffer telomere erosion and enter replicative senescence. The latter is characterized by the accumulation of highly differentiated T-cells with new acquired functional capabilities, which can be caused by aberrant expression of genes normally suppressed by epigenetic mechanisms in CD4+ or CD8+ T-cells. Age-dependent demethylation and overexpression of genes normally suppressed by DNA methylation have been demonstrated in senescent subsets of T-lymphocytes. Thus, T-cells, principally CD4+CD28(null) T-cells, aberrantly express genes, including those of the KIR gene family and cytotoxic proteins such as perforin, and overexpress CD70, IFN-γ, LFA-1 and others. In summary, owing to a lifetime of exposure to and proliferation against a variety of pathogens, highly differentiated T-cells suffer molecular modifications that alter their cellular homeostasis mechanisms.
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