Long-term persistence of zoster vaccine efficacy.

BACKGROUND: The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. METHODS: Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. RESULTS: The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. CONCLUSIONS: Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.

Safety of zoster vaccine in elderly adults following documented herpes zoster.

BACKGROUND: After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). METHODS: A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. RESULTS: The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥ 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. CONCLUSIONS: These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥ 60 years of age with no contraindications, regardless of a prior history of HZ.

Axillary abscess due to Yersinia enterocolitica.

Yersinia enterocolitica rarely causes extraintestinal disease. A 54-year-old construction worker with chronic hepatitis C developed an axillary abscess following an injury to his finger. An aspirate from the axillary mass grew Y. enterocolitica. Direct inoculation is proposed as the mode of transmission of this classically enteric pathogen.

Signal transduction and nuclear responses in Staphylococcus aureus-induced expression of human beta-defensin 3 in skin keratinocytes.

The human beta-defensin 3 (hBD-3) is an inducible epithelial peptide antibiotic that has potent antistaphylococcal activity. Infection of skin epithelial cells with viable Staphylococcus aureus, a common skin pathogen, induces increased gene expression of hBD-3 and other antimicrobial peptides. The aim of this study was to identify signaling pathways and nuclear responses that contribute to the gene expression of hBD-3 in primary human keratinocytes upon contact with S. aureus. Increased hBD-3 peptide was observed by immunofluorescence microscopy in keratinocytes exposed to S. aureus and to lipoteichoic acid (LTA). Both are ligands for the cell surface Toll-like receptor 2 (TLR2), and thus the contribution of TLR2 signaling in hBD-3 expression was examined. Functional inhibition of TLR2 prior to S. aureus stimulation significantly decreased hBD-3 mRNA levels by 37%, attesting to the involvement of this surface receptor in the initial recognition and downstream signaling for hBD-3 expression. Treatment of keratinocytes with a p38 mitogen-activated protein kinase (MAPK) inhibitor prior to either S. aureus or LTA stimulation was associated with reduced hBD-3 mRNA transcripts and peptide. We also propose a role for the MAPK-regulated transcriptional activating protein 1 in S. aureus-induced hBD-3 gene expression. Combined, these studies indicate a role for TLR2 signaling and MAPK activation in the upregulation of hBD-3 and demonstrate the innate immune capacity of skin keratinocytes under conditions of S. aureus challenge to enhance the local expression of this antistaphylococcal peptide antibiotic.

Staphylococcus aureus infection of epidermal keratinocytes promotes expression of innate antimicrobial peptides.

Keratinocytes upregulate expression of endogenous antimicrobial peptides in response to inflammatory stimuli. We show that both viable and heat-inactivated Staphylococcus aureus and lipoteichoic acid differentially alter expression of these peptides upon contact with human keratinocytes. The findings indicate a diversity of staphylococcal factors involved in upregulation of antimicrobial peptide expression in cutaneous epithelia.

The role of fibronectin binding proteins in the pathogenesis of Staphylococcus aureus infections.

PURPOSE OF REVIEW: Staphylococcus aureus produces two closely-related fibronectin-binding proteins (FnBPs) that facilitate attachment by this versatile pathogen. Recent studies of staphylococcal FnBP have increased our understanding of the molecular mechanisms that are critical in bacterial-host cell interactions and in infection. RECENT FINDINGS: This review will summarize current knowledge of the role of the FnBPs of Staphylococcus aureus in the pathogenesis of infection. The FnBPs, which facilitate attachment of this pathogen to host cells and to fibronectin-coated biomaterials, are important mediators of infection in experimental endocarditis. In addition, recent vaccine studies utilizing FnBP derivatives have shown partial protection in animals. FnBPs also act as invasins permitting uptake of the staphylococcus by cultured non-professional phagocytes using host fibronectin to bridge with integrins on the cell surface. However, the precise role of FnBP in tissue invasion and the relevance of intracellular invasion in disease remain to be elucidated. SUMMARY: FnBP is one of many adhesins expressed by S. aureus that influence host tissue adherence by binding to host fibronectin. FnBP-based vaccine strategies and novel anti-adherence tools based upon FnBP derivatives are in the early stages of investigation but may show promise in preventing staphylococcal infections.

Inhibition of staphylococcal wound infection and potentiation of antibiotic prophylaxis by a recombinant fragment of the fibronectin-binding protein of Staphylococcus aureus.

Adherence of Staphylococcus aureus to host tissues is a critical step for colonization and initiation of infection. The fibronectin-binding proteins (FnBPs) of S. aureus have been implicated in adherence and internalization in nonprofessional phagocytes. A recombinant fragment of the fibronectin-binding domains (rFnBF) that potently inhibits S. aureus entry into host cells was generated. To test the hypothesis that rFnBF may attenuate the establishment of infection, the ability of intermuscularly administered rFnBF to prevent abscess formation was determined in a guinea pig model of wound infection. rFnBF exhibited dose-dependent inhibition of abscess formation and, at a 100-microg dose, raised the median infective dose approximately 170-fold, compared with the control. In addition, rFnBF potentiated the benefit of prophylaxis with cefazolin. Thus, exogenous administration of the fibronectin-binding domain of FnBP reduces the risk of staphylococcal abscess formation and should be investigated further as a novel agent for prevention of wound infection.