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Biomedical subjects

D C Powers

Publications and source records attributed to D C Powers.

At least 19 recordsLinked to original sources
PubMed1995

Influenza A virus vaccines containing purified recombinant H3 hemagglutinin are well tolerated and induce protective immune responses in healthy adults.

This study evaluated the safety, immunogenicity, and protective efficacy of vaccines containing purified recombinant uncleaved hemagglutinin (rHA0) from influenza A/Beijing/32/92 (H3N2) virus. In a randomized, double-blinded trial, 127 adult volunteers were immunized with 15 micrograms of rHA0, 15 micrograms of rHA0 plus alum, 90 micrograms of rHA0, licensed subvirion vaccine, or saline placebo. The rHA0 vaccines caused fewer local adverse reactions than did the commercial subvirion preparation. Neutralizing hemagglutinin-specific antibody responses to 15 micrograms of rHA0 were comparable to those elicited by licensed vaccine, not enhanced by the addition of alum, and significantly increased by raising the rHA0 dose from 15 to 90 micrograms. Compared with placebo recipients, rHA0-vaccinated subjects had significantly lower rates of influenza A (H3N2) virus infection and illness during the epidemic winter season. These results suggest that influenza vaccines containing purified rHA0 may offer an advantage over licensed preparations containing egg-grown antigens by inducing equivalent protective immune responses while being potentially less reactogenic.

Adult↗
PubMed1995

Increased anti-influenza A virus cytotoxic T cell activity following vaccination of the chronically ill elderly with live attenuated or inactivated influenza virus vaccine.

The possible enhancement of anti-influenza A virus memory cytotoxic T cell (CTL) responses to inactivated influenza virus vaccine by coadministration of intranasal live attenuated influenza A virus vaccine was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomly assigned to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. A larger proportion of volunteers who received live attenuated virus vaccine than of those who received placebo experienced a postvaccination rise in anti-influenza A virus CTL activity (15 of 23 vs. 8 of 24; P < .05). Anti-influenza A virus cytotoxicity was primarily mediated by CD8+ T cells and was influenza A virus-specific and HLA-restricted. There was a possible advantage of administering live attenuated with inactivated virus vaccine because of enhanced memory anti-influenza A virus CTL activity.

Aged↗
PubMed1995

Cytotoxic T lymphocyte responses to a liposome-adjuvanted influenza A virus vaccine in the elderly.

This randomized double-blind study evaluated cytotoxic T lymphocyte (CTL) responses of elderly volunteers after parenteral immunization with either liposome-adjuvanted (n = 23) or control subvirion (n = 26) vaccine containing detergent-split influenza A/Taiwan/1/86 (H1N1) virus. Peripheral blood mononuclear cells obtained 0, 2, and 12 weeks after vaccination were stimulated in vitro with influenza A (H1N1) virus-infected autologous cells and then assayed for influenza virus-specific cytotoxicity using autologous virus-infected target cells. CTL responses to vaccination exhibited influenza A virus heterosubtypic cross-reactivity and were mediated primarily by CD8+ effector cells. Anti-influenza virus CTL activity was enhanced to a significantly greater extent by the liposome vaccine than by the control subvirion vaccine. It remains to be established whether the advantage of a liposomal formulation in terms of an improved CTL response is relevant to vaccine protective efficacy.

Adjuvants, Immunologic↗
PubMed1994

Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine.

We previously reported an age-associated impairment of serum immunoglobulin G (IgG) antibody responses to inactivated influenza virus vaccine. The present study extends these observations by examining the IgG subclass distribution of vaccine responses measured by enzyme linked immunosorbent assay in healthy adults aged < 40 (young), 40-64 (middle-aged), and > or = 65 (elderly) years. Serological responses in all age groups showed antibodies that were predominantly IgG1 and secondarily IgG3. Influenza antigen-specific IgG4 titers did not change following vaccination, and antibodies of the IgG2 subclass were not detected in any serum specimens. Aging was associated with a significant impairment of IgG1, but not of IgG3, antibody production. Relative differences in the magnitude and frequency of response between IgG1 and IgG3 subclasses, which were present in young and middle-aged adults (viz., IgG1 > IgG3), were less apparent in the elderly. This observation was confirmed in a second analysis of IgG subclass-specific responses in a separate cohort of elderly vaccinees. These results suggest that the age-related impairment of humoral responses to inactivated influenza virus vaccine is primarily accounted for by differences in IgG1 antibody production, and that IgG3 antibodies make up a larger proportion of the overall serologic response in the elderly than they do in younger persons.

Adult↗
PubMed1994

Vaccine-induced antibodies to heterologous influenza A H1N1 viruses: effects of aging and "original antigenic sin".

Prototype influenza A H1N1 viruses representing antigenically distinct Hsw1, H0, and H1 hemagglutinin variants that circulated during the early 1900s were used to measure cross-reactive serum hemagglutination inhibition antibodies elicited by contemporary inactivated virus vaccines in adults aged < 40 (young), 40-64 (middle-aged), or > or = 65 (elderly) years. Elevated titers of antibodies to Hsw1 and H0 antigens were present both before and after vaccination in higher proportions of middle-aged and elderly than young adults, whereas antibodies to more recent H1 antigens were prevalent in all age groups. Vaccine responses to heterologous H1N1 viruses were consistently reduced in frequency and magnitude with advancing age. Also, within each age group, antibody responses tended to diminish against progressively older heterologous antigens. These results confirm previous seroepidemiological surveys but suggest that preferential orientation of secondary antibodies toward priming epitopes ("original antigenic sin") is not responsible for the age-related impairment of antibody responses to influenza vaccine.

Adult↗
PubMed1994

Increased immunogenicity of inactivated influenza virus vaccine containing purified surface antigen compared with whole virus in elderly women.

Thirty-eight elderly female subjects (aged 80 +/- 7 years, mean +/- standard deviation) were randomized to immunization with trivalent inactivated influenza virus vaccine containing either purified surface antigen (n = 18) or whole virus (n = 20) components from A/Texas/36/91 (H1N1), A/Beijing/353/89 (H3N2), and B/Panama/45/90 strains. Humoral and cellular immune responses were assessed by measuring serum hemagglutination inhibition antibodies and cytotoxic T lymphocyte (CTL) activity at 0 and 3 weeks postvaccination. Serological responses to both of the type A vaccine strains following immunization with surface antigen vaccine (SAV) were significantly more frequent and greater in magnitude than those induced by whole-virus vaccine. Antibody responses to the B/Panama component were modest and did not differ significantly between the two vaccines. Persons given SAV, but not those given whole-virus vaccine, had a small but significant increase in mean percent specific lysis of influenza A (H1N1) virus-infected autologous targets by peripheral blood mononuclear cells which were stimulated in vitro with influenza A (H1N1) virus. The H1N1-stimulated cytotoxic effectors induced by SAV were CD8+ and were not cross-reactive against H3N2-infected targets. Influenza B virus-specific CTL responses were not observed with either vaccine. These results suggest that currently available subunit influenza virus vaccines may offer an advantage over inactivated whole-virus preparations for inducing humoral and cellular immune responses in the elderly, although the CTL response may be too limited to be of physiological significance.

Aged↗
PubMed1992

Age-related changes in LFA-1 expression, cell adhesion, and PHA-induced proliferation by lymphocytes from senescence-accelerated mouse (SAM)-P/8 and SAM-R/1 substrains.

Accelerated senescence-prone mice of the SAM-P/8jf series were compared with senescence-resistant SAM-R/1 controls in terms of age-related changes in phytohemagglutinin (PHA) proliferative responses and lymphocyte function-associated antigen-1 (LFA-1) utilization by non-adherent splenocytes. Advancing age was associated with a reduction in cell proliferative responses to PHA in both substrains, although the rate of decline was significantly more rapid in the senescence-prone animals. Conversely, in both substrains there was a progressive age-related increase in the proportion of splenocytes expressing high levels of LFA-1, and a parallel increase in the degree of LFA-1-dependent cell aggregation induced by phorbol ester. Age-matched SAM-P/8jf and SAM-R/1 mice did not differ in terms of LFA-1 expression or LFA-1-dependent cell aggregation. Two-color cytofluorometric analysis demonstrated the enhanced expression of LFA-1 expression by cells bearing the Pgp-1hi phenotype characteristic of memory lymphocytes. These results suggest that age-associated changes in lymphocyte adhesion are attributable to alterations in the relative numbers of memory cells expressing high levels of LFA-1, but are unlikely to contribute to the reduced proliferative response to mitogen in aged mice.

Aging↗
PubMed1992

Reduced infectivity of cold-adapted influenza A H1N1 viruses in the elderly: correlation with serum and local antibodies.

OBJECTIVE: To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus. DESIGN: Time series, comparing outcomes in young and elderly convenience sample. METHOD: Retrospective laboratory analysis of serum and nasal wash specimens collected during prior studies in which young or elderly volunteers had been inoculated with cold-adapted influenza A/Kawasaki/86 (H1N1) reassortant virus. SETTING: Johns Hopkins Center for Immunization Research. PARTICIPANTS: Healthy young and elderly adults with pre-vaccination serum hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8. OUTCOME MEASUREMENTS: Antibody responses in serum and nasal washes. MAIN RESULTS: The proportion of vaccinees who developed any serum or local antibody response was higher in young compared with elderly subjects (20/20 vs 5/14, P less than 0.0005). Resistance to infection with cold-adapted virus correlated with pre-vaccination levels of serum immunoglobulin G (IgG), serum IgA, and nasal wash IgA antibody to whole virus antigen. Age was highly correlated with a lack of response to vaccine by simple regression, but not when data were adjusted for pre-existing antibody levels. CONCLUSIONS: Cold-adapted reassortant influenza A H1N1 viruses achieve lower rates of infection in elderly than young adults, primarily due to age-related differences in preexisting levels of immunity which may not be reflected by HAI titer.

Administration, Intranasal↗
PubMed1991

In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory.

In a double-blind, randomized trial, 102 healthy elderly subjects were inoculated with one of four preparations: (i) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 (H1N1) and cold-adapted A/Bethesda/85 (H3N2) viruses; (ii) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 (H1N1), A/Leningrad/86 (H3N2), and B/Ann Arbor/86 antigens; (iii) both vaccines; or (iv) placebo. To determine whether local or systemic immunization augmented mucosal immunologic memory, all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine. We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G (IgG) and IgA antibodies in sera and nasal washes, respectively. In comparison with the live virus vaccine, the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies, while nasal wash antibody responses were similar. The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did. Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine. The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live, inactivated, or combined vaccine groups from that observed in the placebo group not previously immunized. These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory. Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group.

Administration, Intranasal↗
PubMed1989

Expression of interleukin 2 and the interleukin 2 receptor in aging rats.

Lymphocytes of aged animals exhibit a marked decrease in proliferative capacity in response to mitogen stimulation when compared to those of younger animals. In humans and mice the decreased proliferation is due at least in part (i) to the inability of lymphocytes to synthesize sufficient interleukin 2 (IL-2) and (ii) to decreased expression of IL-2 receptors (IL-2R) on the surface of aged lymphocytes. We compared proliferative abilities, IL-2 production, and IL-2R expression in splenocyte cultures of 4- to 5- and 22- to 24-month-old Fischer 344 rats stimulated with either concanavalin A (Con A) or A23187 and phorbol myristate acetate (PMA). Proliferation was significantly decreased in aged lymphocytes (30-50%) with both treatment protocols. However, unlike mice and humans we observed no difference in IL-2 activity, IL-2 mRNA levels, or IL-2R cell surface expression of lymphocytes from young and aged rats stimulated with either Con A or A23187 and PMA. These results indicate that factors other than decreased expression of IL-2 and IL-2R are responsible for the diminished proliferative capacity of aged rat lymphocytes following mitogen stimulation.

Aging↗
PubMed1989

Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans.

The levels of interleukin 2 (IL-2), interleukin 2 receptor (IL-2R), and interferon-gamma (IFN-gamma) specific mRNA and their gene products were examined in phorbol myristate acetate (PMA) and calcium ionophore A23187-costimulated purified T cells from young and elderly humans. In addition, the number of high-affinity IL-2R per activated cell, the high-affinity IL-2R density, and the proliferative response of the cells were measured. Among PMA/A23187-stimulated T cells, there was no statistically significant age-related difference in IL-2 or IL-2R specific mRNA accumulation or in the amount of IL-2 or IL-2R synthesized. IFN-gamma specific mRNA was increased significantly in T cells from elderly individuals and the amount of IFN-gamma synthesized by PMA/A23187-activated T cells was nearly double that produced by cells from young individuals. Quantification of the number of high-affinity IL-2R by [125I]IL-2 binding demonstrated there was no decrease in either the mean number or the dissociation constant of the high-affinity IL-2R on activated T cells of the elderly. Despite producing large amounts of IL-2 and having comparable numbers of both low- and high-affinity IL-2R. PMA/A23187-stimulated T cells from elderly subjects still proliferated less vigorously than did T cells from young persons. The addition of exogenous IL-2 to the cultured cells did not fully correct this age difference. Our findings that the expression of the IL-2, IL-2R, and IFN-gamma genes are not constitutionally defective in the elderly support the hypothesis that the age-related decline in proliferation observed in mitogen-stimulated T cells of the elderly is most likely attributable to alterations in the transmission of signals from the cell membrane to the nucleus.

Adult↗
PubMed1989

Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines.

Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects. An enzyme-linked immunosorbent assay was used to measure hemagglutinin-specific (HA) antibodies in serum and nasal wash specimens collected before vaccination and 1 and 3 months later. Serum immunoglobulin G (IgG) and nasal wash IgA HA responses were elicited in 56 and 20%, respectively, of 25 inactivated-virus vaccinees and in 67 and 48%, respectively, of 27 recipients of both vaccines but in only 36 and 25%, respectively, of 28 vaccinees given live virus alone. Inactivated virus, administered alone or with live virus vaccine, induced higher titers of serum antibody than did the live virus alone. In contrast, nasal IgA HA antibody was elicited more often and in greater quantity by the vaccine combination than by either vaccine alone. Despite these differences, the peak titers of local antibody mounted by each group of vaccinees were similar. By 3 months postvaccination, serum IgG and nasal IgA HA antibody titers remained elevated above prevaccination levels in 50 and 17%, respectively, of the inactivated-virus vaccinees and in 46 and 23%, respectively, of recipients of both vaccines but in only 19 and 7%, respectively, of the live-virus and systemic antibodies, if vaccinees. The finding that live ca influenza A virus induced short-lived local and systemic antibodies, if confirmed, suggests that live virus vaccination may not be a suitable alternative or adjunct to inactivated virus vaccination for the elderly.

Aged↗
PubMed1989

Soluble interleukin 2 receptors released from mitogen stimulated human peripheral blood lymphocytes bind interleukin 2 and inhibit IL2 dependent cell proliferation.

In this communication the binding characteristics and possible regulatory role of sIL2R were investigated. Soluble IL2R are released or secreted in high concentrations by phytohemagglutinin (PHA) stimulated human lymphoid cells. The addition of sIL2R, purified by gel filtration chromatography, to cultures of PHA stimulated lymphoblasts resulted in a dose-dependent inhibition of [3H]TdR incorporation that could be overcome by the addition of exogenous IL2. Scatchard analysis of IL2 binding demonstrated that the presence of sIL2R did not inhibit ligand interaction with the high affinity IL2R. Immunoprecipitation studies utilizing [125I]IL2 and the non-inhibitory anti-Tac protein antibody 7G7/B6 revealed that most of the 125I-labeled IL2 migrated with a protein of approximately 45-50 kDa on SDS/PAGE. Together, these results provide evidence that the sIL2R limits the availability of free IL2 to proliferating cells and down-regulates their response without directly affecting the number or function of the cell bound high affinity IL2R.

Cell Division↗
PubMed1989

Effect of age on the human high affinity interleukin 2 receptor of phytohaemagglutinin stimulated peripheral blood lymphocytes.

High affinity interleukin 2 receptors (HA-IL-2R) on mitogen- or antigen-stimulated T cells have been shown to efficiently bind interleukin 2 (IL-2) and to transduce the activation signal(s) that facilitate proliferation. This study was initiated to determine whether the impaired proliferative response of T cells from elderly individuals can be attributed to the defective expression of HA-IL-2R. While cells from both young and old individuals had statistically insignificant differences in the number of HA-IL-2R per membrane IL-2R-positive cell and these receptors displayed similar binding affinities with 125I-IL-2, there were consistently fewer cells and fewer cells expressing HA-IL-2R in the cell cultures from elderly individuals. The magnitude of the age-associated impairment in cell proliferation was decreased, but remained present, when Percoll fractionated lymphoblasts, as compared to peripheral blood lymphocytes (PBL), were cultured in the presence of exogenous interleukin 2 (IL-2). The results demonstrate that a significantly larger percentage of lymphocytes from elderly individuals do not respond to mitogenic stimulation and, probably due to stimulus stress, die in culture. As a consequence there are fewer functionally competent cells expressing the HA-IL-2R in cultures from elderly individuals, which in turn contributes to the age-related defect in the lymphocyte proliferative response.

Adult↗
PubMed1987

Influenza, pneumonia, tetanus: how effective is vaccination?

The rationale for immunizing older adults with influenza, pneumococcal, and tetanus-diphtheria vaccines is derived largely from epidemiological data indicating a heightened susceptibility to these illnesses within this population. The authors provide supportive information relevant to the routine use of these vaccines in adults aged 65 or older.

Aged↗
PubMed1986

Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia.

Twenty-six patients with sleep apnea had neuropsychologic testing prior to nocturnal sleep study in a sleep disorders clinic. The cognitive functioning of patients who had sleep apnea with associated hypoxemia was compared to nonhypoxemic patients with sleep apnea. The patients who had sleep apnea with hypoxemia had more severe cognitive impairment than those with sleep apnea without hypoxemia. The hypoxemic patients with sleep apnea had significantly poorer cognitive functioning on four of eight tests (p less than 0.05). In addition, the patients who had sleep apnea with hypoxemia had mean performance scores in the impaired range on measures of attention, concentration, complex problem-solving, and short-term recall of verbal and spatial information. In contrast, the patients who had sleep apnea without hypoxemia had no mean performance score in the impaired range. The degree of hypoxemia during sleep and wakefulness significantly correlated with the degree of overall cognitive impairment as rated by a neuropsychologist; however, measures of sleep fragmentation did not significantly correlate with overall cognitive impairment in patients with sleep apnea. We conclude that patients who have sleep apnea with associated hypoxemia have cognitive impairment which is more severe than those with sleep apnea without hypoxemia.

Cognition Disorders↗