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Biomedical subjects

Janet E McElhaney

Publications and source records attributed to Janet E McElhaney.

11 recordsLinked to original sources
PubMed2006

T cell responses are better correlates of vaccine protection in the elderly.

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-gamma:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Adult↗
PubMed2006

Efficacy of COLD-fX in the prevention of respiratory symptoms in community-dwelling adults: a randomized, double-blinded, placebo controlled trial.

BACKGROUND: COLD-fX (CVT-E002), a proprietary extract of the roots of North American ginseng (Panax quinquefolium), rich in poly-furanosyl-pyranosyl-saccharides, has been found efficacious in the prevention of respiratory infections in institutionalized seniors and healthy adults. OBJECTIVE: We examined the efficacy of COLD-fX in the prevention of acute respiratory illness (ARI) in community dwelling seniors. DESIGN: This was a randomized, double-blind, placebo controlled trial. INTERVENTION: The participants were asked to take 2 capsules/day of either COLD-fX or placebo (200 mg/ capsule) for a period of 4 months. SUBJECTS: A total of 43 community-dwelling adults aged 65 years or older were recruited. Following one month of intervention, subjects were immunized with influenza vaccine. OUTCOME MEASURES: Subjects recorded the incidence and duration of respiratory symptoms during the study. They also recorded the incidence of adverse events during the study. RESULTS: The frequency and duration of ARI during the first two months of the study was found to be similar in the two groups. However, during the last 2 months (November and December) significantly fewer subjects in the COLD-fX group 32% reported ARI compared to the placebo group 62%. The duration of symptoms during the last 2 months was significantly shorter in the COLD-fX group than the placebo group (5.6 days in the COLD-fX group vs 12.6 days in the placebo group). There was no influenza illness circulating in the community during the period of the study. CONCLUSIONS: Ingestion of COLD-fX by immunocompetent seniors during an early "cold and flu" season reduced the relative risk and duration of respiratory symptoms by 48% and 55%, respectively. Daily COLD-fX administration can thus be a safe, natural therapeutic means for the prevention of ARI in healthy seniors.

Aged↗
PubMed2005

The unmet need in the elderly: designing new influenza vaccines for older adults.

Influenza is a serious illness and probably the single most important cause of excess disability and mortality during the winter months. In spite of limited efficacy in older adults, influenza vaccination is nevertheless a cost-saving medical intervention since it does reduce hospitalisation and death rates due to pneumonia, exacerbations of heart failure and, surprisingly, heart attacks and strokes. Yet hospitalisation and death rates for acute respiratory illnesses continue to rise in spite of widespread vaccination programs. As a person ages, the immune response to antigenic stimulation with the influenza virus shifts toward T helper type 2 cytokine production. This is associated with a relative reduction in cytotoxic T-cell activity and a reduced capacity to destroy infected host cells and clear the virus from infected lung tissue. Breakthrough strategies to improve the current influenza vaccines are required to avoid a crisis in health care. A targeted approach will develop vaccines that can reverse these age-related changes in T-cell responses, particularly the functions of cytotoxic T lymphocytes.

Aged↗
PubMed2005

Comparison of single versus booster dose of influenza vaccination on humoral and cellular immune responses in older adults.

This study compared the immune response to the standard single-dose (SD) of influenza vaccine to a booster dose (BD) re-vaccination given 16 weeks after the initial dose. While seroprotection rates following vaccination were similar, T-cell responses were more optimally stimulated in the SD versus the BD group. SD lead to a greater than 10-fold decline in ex vivo interleukin-10 (IL-10) levels (P < .0001) and a corresponding significant increase in the interferon-gamma (IFN-gamma) to IL-10 ratio. Although BD had no further effect on IL-10 production, the IFN-gamma:IL-10 ratio declined in the BD group (P < .001, A/H3N2 and B strains). In the SD group only, IFN-gamma:IL-10 ratios significantly correlated with serum antibody titers (R = .37 - .50, P < or = .01) and ex vivo granzyme B (Grz B) levels (R = .50-.65, P < or = .001). Following vaccination, granzyme B levels were significantly higher in the SD compared to the BD group (P < or= .0002). These results suggest that SD influenza vaccine produces Th1 and CTL responses while BD may produce a Th2 response that poorly stimulates the CTL response.

Aged↗
PubMed2004

Effect of congestive heart failure on humoral and ex vivo cellular immune responses to influenza vaccination in older adults.

This study examined the effect of congestive heart failure (CHF) on immune responses to influenza vaccination (2000-2001 preparation) in three groups of older adults including healthy, Class II and Class III/IV CHF. Serum antibody titers measured by hemagglutination inhibition (HI), and interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and granzyme B (GrzB) levels in ex vivo virus-activated mononuclear cell cultures showed significant responses from pre-vaccination to 4 and 12 weeks post-vaccination (P<0.01). There was a trend for lower GrzB and higher IFN-gamma and IL-10 levels in healthy versus CHF groups (P<0.06) for all viral strains at 4 weeks. HI titers did not differ between groups. In the regression model, Grz B levels were significantly predicted by the IFN-gamma:IL-10 ratio and performance on the 6 min Walk Test; age and CHF dropped out of the model. In conclusion, CHF in older adults predicts GrzB responses to influenza vaccination due to cytokine and physical ability differences.

Aged↗
PubMed2004

Mood and cytokine response to influenza virus in older adults.

BACKGROUND: Previous research has indicated that older adults with severe life stress show attenuated immune responses to influenza vaccination. Associations among mood, optimism, stress, and the in vitro cytokine response to influenza virus and vaccine were evaluated in 18 healthy older adults with low to moderate life stress. METHODS: Peripheral blood mononuclear cells were stimulated in cultures with 1999-2000 influenza vaccine viruses (A/Beijing/262/95, A/Sydney/5/97, and B/Yamanashi/166/98) and the 2000-2001 trivalent vaccine (containing A/New Caledonia/20/99, A/Panama/2007/99, and B/Yamanashi/166/98). The levels of T-helper type 1 (interleukin-2 and interferon-gamma) and type 2 (interleukin-10) cytokines were measured in culture supernatants. RESULTS: Stress, age, and current health practices were unrelated to cytokine production. Older adults reporting greater anger, fatigue, confusion, and total mood disturbance had poorer cytokine responses to live virus and vaccine stimulation. In contrast, older adults who reported greater vigor and those who were more optimistic had greater cytokine responses to both live virus and vaccine. These relationships were largely unaffected by medications or health conditions. CONCLUSIONS: These findings suggest that among older adults, even mild to moderate mood disturbance is associated with an attenuated cellular immune response to live influenza virus and vaccine.

Aged↗
PubMed2004

A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults.

OBJECTIVES: To compare a proprietary extract of American ginseng, CVT-E002, with placebo in preventing acute respiratory illness (ARI) in an institutional setting during the influenza season. DESIGN: Two randomized, double-blind, placebo-controlled trials conducted late in the 2000 (8 week) and 2000-2001 (12 week) influenza seasons. SETTING: Long-term care setting that included nursing home and assisted living at three sites. PARTICIPANTS: Eighty-nine (2000) and 109 (2000-2001) enrolled subjects, average age 81 and 83.5, respectively; 74% women. Approximately 90% had received influenza vaccine in each of the 2 years. INTERVENTION: Oral twice-daily administration of a proprietary ginseng extract, CVT-E002, 200 mg or placebo. MEASUREMENTS: ARI was defined as two new respiratory symptoms or one with a constitutional symptom. Confirmation of viral ARI was by culture (influenza or respiratory syncytial virus (RSV)) or serology for influenza. Laboratory safety monitoring was done at 0, 4, and 8 or 12 weeks. RESULTS: An intent-to-treat analysis of pooled data corrected for drug exposure time showed that the incidence of laboratory-confirmed influenza illness (LCII) was greater in placebo- (7 cases/101 subjects) than CVT-E002-treated (1/97) groups (odds ratio (OR)=7.73, P=.033). Combined data for LCII and RSV illness were also greater in placebo- (9/101) than CVT-E002-treated (1/97) groups (OR=10.50, P=.009), for an overall 89% relative risk reduction of ARI in the CVT-E002 group. CONCLUSION: CVT-E002 was shown to be safe, well tolerated, and potentially effective for preventing ARI due to influenza and RSV.

Acute Disease↗
PubMed2003

A novel cytotoxicity assay to evaluate antigen-specific CTL responses using a colorimetric substrate for Granzyme B.

We have utilized the unique enzymatic properties of a key cytotoxic mediator in target cell destruction, Granzyme B (GrB), to establish an attractive alternative to 51Cr-release assays for the assessment of antigen-specific CTL responses. A number of potential colorimetric peptide substrates were compared to evaluate levels of GrB activity in cytolytic cells. The most specific and sensitive substrate for GrB was Ac-IEPD-pNA, as shown by the minimal enzymatic hydrolysis in apoptotic Jurkat cells and strong hydrolysis in human NK cells. When human peripheral blood lymphocytes were stimulated in vitro, elevated GrB levels were detected by both Ac-IEPD-pNA and a GrB ELISA. Analysis of allo-antigen-specific murine CTLs revealed that GrB exocytosis was only detectable upon challenge with appropriate allogeneic target cells and strongly correlated to 51Cr-release data. The validity of using Ac-IEPD-pNA in vaccine trials was demonstrated in mice immunized with allogeneic P815 cells, where GrB enzymatic activity was measurable in ex vivo splenocytes cell cultures only upon co-incubation with P815 targets. Additionally, influenza-infected mice were also assessed for GrB activity following in vitro peptide-stimulation of splenocytes and strongly reflected both peptide-specific tetramer staining and 51Cr-release results. The novel cytotoxic assay presented here should give investigators a sensitive, cross-species, nonradioactive alternative to 51Cr-release assays as a means to assess antigen-specific CTL responses in vaccine trials.

Anilides↗
PubMed2003

Overcoming the challenges of immunosenescence in the prevention of acute respiratory illness in older people.

This article describes the impact of acute respiratory illness (ARI) and the challenges to primary prevention of viral ARI and related morbidity in the age 65 and older population. Immunosenescence, the immune system's "memory loss" with aging, compromises both host defense mechanisms against ARI and effective responses to vaccination. Atypical presentations of illness common in older people often lead to delayed or missed diagnoses of ARI and disabling consequences. Thus, preventing ARI will be more effective than treatment. Even with the limited efficacy of current influenza vaccines in older people, vaccination is a cost-saving intervention especially in high-risk groups including those with chronic heart or lung diseases. Significant opportunities to further reduce the morbidity of ARI include developing more effective influenza vaccines and vaccines against other ARI. Combining vaccination with antiviral or immunoenhancing agents particularly in high-risk groups could optimize the cost benefit of additional preventive strategies.

Aged↗