Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis.

BACKGROUND: Many adult immunization schedules recommend that tetanus and diphtheria vaccination be performed every 10 years. In light of current epidemiological trends of disease incidence and rates of vaccine-associated adverse events, the 10-year revaccination schedule has come into question. METHODS: We performed cross-sectional analysis of serum antibody titers in 546 adult subjects stratified by age or sex. All serological results were converted to international units after calibration with international serum standards. RESULTS: Approximately 97% of the population was seropositive to tetanus and diphtheria as defined by a protective serum antibody titer of ≥0.01 IU/mL. Mean antibody titers were 3.6 and 0.35 IU/mL against tetanus and diphtheria, respectively. Antibody responses to tetanus declined with an estimated half-life of 14 years (95% confidence interval, 11-17 years), whereas antibody responses to diphtheria were more long-lived and declined with an estimated half-life of 27 years (18-51 years). Mathematical models combining antibody magnitude and duration predict that 95% of the population will remain protected against tetanus and diphtheria for ≥30 years without requiring further booster vaccination. CONCLUSIONS: These studies demonstrate that durable levels of protective antitoxin immunity exist in the majority of vaccinated individuals. Together, this suggests that it may no longer be necessary to administer booster vaccinations every 10 years and that the current adult vaccination schedule for tetanus and diphtheria should be revisited.

Interleukin-1ß mediates virus-induced m2 muscarinic receptor dysfunction and airway hyperreactivity.

Respiratory viral infections are associated with the majority of asthma attacks. Inhibitory M2 receptors on parasympathetic nerves, which normally limit acetylcholine (ACh) release, are dysfunctional after respiratory viral infection. Because IL-1ß is up-regulated during respiratory viral infections, we investigated whether IL-1ß mediates M2 receptor dysfunction during parainfluenza virus infection. Virus-infected guinea pigs were pretreated with the IL-1ß antagonist anakinra. In the absence of anakinra, viral infection increased bronchoconstriction in response to vagal stimulation but not to intravenous ACh, and neuronal M2 muscarinic receptors were dysfunctional. Pretreatment with anakinra prevented virus-induced increased bronchoconstriction and M2 receptor dysfunction. Anakinra did not change smooth muscle M3 muscarinic receptor response to ACh, lung viral loads, or blood and bronchoalveolar lavage leukocyte populations. Respiratory virus infection decreased M2 receptor mRNA expression in parasympathetic ganglia extracted from infected animals, and this was prevented by blocking IL-1ß or TNF-α. Treatment of SK-N-SH neuroblastoma cells or primary cultures of guinea pig parasympathetic neurons with IL-1ß directly decreased M2 receptor mRNA, and this was not synergistic with TNF-α treatment. Treating guinea pig trachea segment with TNF-α or IL-1ß in vitro increased tracheal contractions in response to activation of airway nerves by electrical field stimulation. Blocking IL-1ß during TNF-α treatment prevented this hyperresponsiveness. These data show that virus-induced hyperreactivity and M2 dysfunction involves IL-1ß and TNF-α, likely in sequence with TNF-α causing production of IL-1ß.

TNFR and LTbetaR agonists induce follicle-associated epithelium and M cell specific genes in rat and human intestinal epithelial cells.

M cells assist mucosal immune surveillance by transcytosis of particles to underlying lymphoid tissue, but the mechanisms of M cell differentiation are poorly understood. To develop a better defined cell culture model of M cell differentiation, we treated human (Caco-2BBe) and rat (IEC-6) intestinal epithelial cell lines with lymphotoxin beta receptor (LTbetaR) and TNF receptor (TNFR) agonists. Treated cells were studied for regulation of genes associated with M cell and follicle-associated epithelium (FAE). We found that LTbetaR and TNFR agonists induce transcription of FAE-specific genes (Ccl20 and Lamb3) in Caco2-BBe cells and IEC-6 cells as well as rodent M cell specific genes such as Sgne-1/Scg5, Cldn4, and Gp2. The cytokines have distinct but complementary effects; TNFR agonists mainly induced FAE-specific genes, while the LTbetaR agonist induced M cell specific genes. The combination of cytokines showed additive induction of the FAE-associated Ccl20, Lamb3 and a surprising induction of CD137/Tnfrsf9. On the other hand TNF agonists appeared to suppress expression of some LTbetaR-induced genes. Functionally, cytokine treatment led to the reorganization of microvilli and Claudin-4 redistribution. These studies suggest complex interactions between these cytokines in the context of either inflammation or tissue differentiation.