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Biomedical subjects

R B Couch

Publications and source records attributed to R B Couch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytotoxic T lymphocyte responses of infants after natural infection or immunization with live cold-recombinant or inactivated influenza A virus vaccine.

The cytotoxic T lymphocyte (CTL) response of infants after immunization with either inactivated trivalent subvirion vaccine (TIV) or bivalent attenuated cold-recombinant (CR) vaccine or occurrence of natural influenza virus infection were compared in a blinded, placebo-controlled study during the 1987-1988 and 1988-1989 influenza epidemic seasons. Healthy infants between 6 and 13 months of age were randomly assigned and administered a single dose of intranasal bivalent (A/H3N2/A/H1N1) CR vaccine, a two-dose regimen of TIV (A/H3N2/A/H1N1/B) influenza vaccine, or placebo. Peripheral blood lymphocytes were obtained prior to and 2-8 weeks after vaccination and at the end of the epidemic season and stimulated with virus in vitro for 6 or 7 days. Lysis of autologous virus-infected target cells was assessed in a 4 hr 51Cr release assay. MHC class I-restricted influenza A-specific CTL was stimulated following natural influenza A virus infection but not after immunization with CR influenza A virus vaccine or TIV. These results demonstrate for the first time induction of influenza virus-specific CTL activity in infants under 1 year of age.

Adult↗
PubMed1996

Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.

From 1 November 1992 through 1 May 1993 and from 1 November 1993 through 1 May 1994, we conducted a prospective surveillance study at the University of Texas M.D. Anderson Cancer Center (Houston) to evaluate the role of community respiratory virus infections in hospitalized adult bone marrow transplant (BMT) recipients, Respiratory secretions were obtained from all adult BMT recipients with acute respiratory illnesses. During these two winters, a community respiratory virus was isolated from 37 (36%) of 102 patients and 30 (26%) of 115 patients, respectively. Approximately half (49%) of these infections were due to respiratory syncytial virus (RSV); the remainder were due to influenza virus (18%), picornaviruses (18%), parainfluenza virus (9%), or adenovirus (6%). Fifty-eight percent of these infections were complicated by pneumonia, with an associated mortality of 51%. The pneumonias that complicated RSV infection were almost exclusively viral in origin and were associated with a mortality of 100% if not treated promptly with antiviral agents. In contrast, many of the pneumonias that complicated the other viral infections, such as influenza, appeared to be either self-limited viral pneumonias or secondary bacterial or fungal pneumonias. Community respiratory viruses are frequent causes of acute respiratory illnesses in adult BMT recipients hospitalized during the winter and are associated with substantial morbidity and mortality.

Adenovirus Infections, Human↗
PubMed1996

Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines enhance antibody responses in the elderly.

The reactogenicities and immunogenicities of two influenza virus vaccines were compared in a placebo-controlled clinical trial among healthy ambulatory persons > or = 65 years old (mean age, 72 years). Volunteers were assigned randomly to receive 15-, 45-, or 135-micrograms doses of monovalent influenza A/Taiwan (H1N1) hemagglutinin (HA) or subvirion (SV) vaccine intramuscularly or a placebo. Increasing doses of SV vaccine were associated with a higher rate of injection site discomfort (P < 0.05; chi-square test for linear trend), but all doses of both vaccines were well tolerated. Increasing the dose of the HA or the SV vaccine resulted in increasingly higher postimmunization levels of serum hemagglutination inhibition and neutralizing antibody levels (P < 0.001; multiple linear regression). Mean serum antibody titers at 1 month increased two- to threefold with a ninefold increase in dose; the frequencies of fourfold or greater rises in titer likewise increased. An increase in the dose of the HA or the SV vaccine also resulted in increased frequencies of rises in immunoglobulin A or G antibody titers in nasal wash specimens. The frequencies increased approximately twofold for each vaccine with a ninefold increase in the dose. These data suggest that increasing the HA vaccine dose is a promising approach to the development of improved influenza virus vaccines for use in elderly people.

Aged↗
PubMed1995

Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans.

The immunogenicity and toxicity of a purified influenza virus (N2) neuraminidase vaccine (NAV) were investigated in 88 human subjects aged 18-40, and compared to response to a conventional trivalent influenza vaccine, Fluogen (Parke-Davis). NAV doses ranged from 2.6 to 69.9 micrograms and were given intramuscularly. Serologic neuraminidase-inhibiting (NI) and neuraminidase-specific ELISA responses in this N2-primed population were roughly proportional to the dose administered. Maximal response was seen in 14-21 days and NI antibody titers persisted unabated for the 6-month post-vaccination follow-up period. All doses were well tolerated with respect to local and systemic reactions. NI tests performed with the putative (1975) priming N2 antigen demonstrated anamnestic response but did not reveal responses not already shown with the homologous (1992) antigen. Response to this purified, non-adjuvanted preparation encourages continuing investigation of the induction of infection-permissive immunity with influenza virus neuraminidase.

Adolescent↗
PubMed1995

Respiratory syncytial virus pneumonia in hospitalized adult patients with leukemia.

Respiratory syncytial virus (RSV) has been demonstrated to be an important cause of life-threatening pneumonia in adult bone marrow transplant recipients; however, its role in other immunocompromised adults has not been defined. We prospectively studied all adult patients with leukemia who were hospitalized at M. D. Anderson Cancer Center (Houston) during a 1-year period (November 1993 through October 1994). During a 19-week period when RSV was prevalent in the community, it was isolated from 9 (10%) of 87 patients with leukemia who developed an acute respiratory illness. In 6 (75%) of 8 patients with profound chemotherapy-induced myelosuppression, the RSV infection was complicated by pneumonia, with an 83% mortality rate. RSV appears to be an important cause of severe and often fatal pneumonia in myelosuppressed patients with leukemia.

Acute Disease↗
PubMed1995

Comparison of trivalent cold-adapted recombinant (CR) influenza virus vaccine with monovalent CR vaccines in healthy unselected adults.

A trivalent cold-adapted recombinant (CR) influenza virus vaccine containing types A and B viruses was compared with monovalent vaccines of each virus in a double-blind, placebo-controlled trial. Adults with a wide range of preexisting antibody titers received one 0.5-mL dose intranasally of trivalent vaccine; monovalent A/H1N1, A/H3N2, or B vaccine; or placebo. All vaccines were well tolerated. Serum antibody response frequencies and postvaccination geometric mean antibody titers were similar for recipients of trivalent or the corresponding monovalent vaccine for each of the vaccine components. Stepwise logistic regression analysis of the antibody responses of trivalent vaccine recipients demonstrated that response to one vaccine virus did not adversely affect the likelihood of response to the other viruses. This study failed to find serologic evidence of interference between vaccine viruses, suggesting that trivalent CR influenza virus vaccine may be useful for preventing influenza in adult populations.

Acclimatization↗
PubMed1994

Influenza A subtype cross-protection after immunization of outbred mice with a purified chimeric NS1/HA2 influenza virus protein.

Influenza A/PR/8/34-derived chimeric (D) protein (SK&F 106160) composed of the first 81 amino acids (aa) of NS1 fused to the conserved 157 C-terminal aa of HA2 (NS1 1-81-HA2 65-222) was previously shown to induce H-2d-restricted protective cytotoxic T-lymphocyte (CTL) immunity in inbred mice. However, D protein, like other small peptides, exhibited haplotype dependence and was not immunogenic in H-2b and H-2K mice. A potential use of this antigen in humans and the role of T cells in any protection were evaluated in outbred Swiss and inbred CBF6F1 (H-2d/b) mice. Mice immunized with D protein and challenged by small-particle aerosol with a lethal dose of influenza virus were significantly protected against mortality from influenza A/H1N1 and A/H2N2 (p < 0.05-< 0.0000001), but not from A/H3N2 and influenza B viruses when compared with control mice. D protein did not induce serum virus-neutralizing antibody but caused virus to be cleared faster in immunized mice. Protection was long-lasting. In vivo depletion of either Lyt2 (CD8+) or L3T4 (CD4+) T cells with monoclonal antibodies led to abrogation of in vitro-generated CTL activity in CF6F1 mice and significant reduction in the protective efficacy of D protein against virus challenge in both Swiss and CF6F1 mice. These results suggest that protection was mediated by CD8+ and/or CD4+ cells and not antibody. Thus D protein, via a conserved sequence on the HA2 polypeptide, has the potential to induce partially cross-reactive CTL that may protect against influenza virus disease in humans.

Aerosols↗
PubMed1994

Quantitation of human influenza virus-specific cytotoxic T lymphocytes: correlation of cytotoxicity and increased numbers of IFN-gamma producing CD8+ T cells.

To study virus-specific cytotoxic T lymphocyte (CTL) activity at the single cell level, an IFN-gamma specific ELISPOT assay was adapted to elucidate the frequency of influenza-specific CTLs together with a standard cytotoxic 51Cr-release assay. Peripheral blood mononuclear cells (PBMCs) from human volunteers were cultured with influenza virus-infected autologous cells; following 3 or 7 days of culture, T cell subsets were assessed for IFN-gamma production by IFN-gamma-specific ELISPOT and ELISA, while IFN-gamma mRNA expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Influenza virus-specific CTL activity was measured in a 4 h 51Cr-release assay. Culture of PBMC with autologous A/Taiwan influenza (H1N1)-infected stimulator cells resulted in IFN-gamma spot forming cells (SFCs) at 3 days that increased after 7 days of incubation. Numbers of IFN-gamma SFCs directly correlated with levels of secreted IFN-gamma and higher levels were seen in supernatants from 7 day cultures. RT-PCR analysis (35 cycles of amplification) showed greater IFN-gamma mRNA in T cells isolated from 7 day cultures. Separate aliquots of T cells from these cultures were also assessed for virus-specific cytotoxicity and T cells from 7 day (but not from 3 day) cultures induced high 51Cr release. Analysis indicated a significant direct correlation between level of cytotoxicity, number of IFN-gamma SFCs, and amount of IFN-gamma in culture supernatants. Studies with purified T cell subsets showed that elevated IFN-gamma SFCs, IFN-gamma synthesis, and cytotoxic activity were associated with CD4-CD8+ T cells but not with the CD4+CD8- T cell subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness.

Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.

Acute Disease↗
PubMed1994

High doses of purified influenza A virus hemagglutinin significantly augment serum and nasal secretion antibody responses in healthy young adults.

The reactogenicity and immunogenicity of purified influenza virus hemagglutinin (HA) vaccines administered intramuscularly were evaluated in two placebo-controlled clinical trials. A total of 139 healthy young adults were randomized to receive increasing doses of monovalent influenza A/Taiwan/1/86 (H1N1) virus HA (range, 0 to 405 micrograms per dose [study 1]). An additional 139 subjects were given increasing doses of a trivalent HA vaccine containing equal amounts of A/H1N1 virus, A/Shanghai/16/89 (H3N2) virus, and influenza B/Yamagata/16/88 virus HA (range, 0 to 135 micrograms of HA per strain, 0 to 405 micrograms per dose) or a standard dose of commercial influenza vaccine (study 2). Increasing doses of HA were associated with increasing frequencies of symptoms at the vaccination site early after vaccination, but all doses were well tolerated. Occurrence of systemic symptoms was unrelated to dose. Increasing the dose of HA resulted in increasingly higher postimmunization levels of serum hemagglutination inhibiting and neutralizing antibody levels versus influenza A/H1N1 virus in study 1 (P < 0.05); these enhanced responses persisted for up to 6 months. Nasal secretory immunoglobulin A and G antibody responses were assessed 2 weeks after immunization with monovalent H1N1 virus HA; the frequencies of significant responses also increased in a dose-related fashion. Similar increases in serum antibody levels were noted for both A/H1N1 and A/H3N2 viruses in study 2. These data provide a basis for proceeding with the evaluation of high doses of purified HA in the elderly.

Adolescent↗
PubMed1994

Influenza A virus infections among hospitalized adult bone marrow transplant recipients.

Although influenza virus continues to cause annual epidemics of respiratory diseases, surprisingly little is known about the frequency and clinical course of influenza among adult patients with cancer. During the 1991-92 influenza epidemic in Houston, Texas, we followed all adult BMT recipients hospitalized at M.D. Anderson Cancer Center. None of these 68 patients had received prophylaxis for influenza. Influenza virus type A was isolated from 8 (29%) of 28 BMT recipients with an acute respiratory illness. Five of these infections were acquired in the hospital. All 8 patients presented with an upper respiratory tract illness. In 6 patients, the infection was complicated by pneumonia. The frequency of influenza was similar among autologous (5 of 18) and allogeneic (3 of 10) BMT recipients. The risk of developing pneumonia was not related to the type of transplant or to the engraftment status. All patients received broad-spectrum antibiotics. The 2 patients who did not develop pneumonia also received amantadine. The mortality with pneumonia was 17%. During community outbreaks, influenza is a frequent cause of acute respiratory illness among hospitalized adult BMT recipients and is frequently complicated by pneumonia. Studies are needed to define the optimal means of preventing and treating influenza in BMT recipients.

Adult↗
PubMed1993

Advances in influenza virus vaccine research.

Influenza epidemics occur annually in the United States and are characterized by high frequencies of illness among children and young adults, high hospitalization rates among infants and older persons, and high death rates among the elderly. Vaccines that can prevent infection must stimulate anti-hemagglutinin antibody in serum and secretions; those that stimulate anti-neuraminidase antibody or T cell cytotoxic responses can reduce the severity of infection and illness or hasten recovery. Advances in vaccine research are permitting evaluation of pure subunit vaccines, new adjuvants, topical immunization, and the use of immunomodulators for enhancing immune responses. In young adults, doses of HA of up to 405 micrograms were well tolerated and provided enhanced antibody responses. Although use of a muramyl-dipeptide derivative as an adjuvant resulted in unacceptable reactogenicity, other adjuvants may be acceptable. Development of topical immunization and immunomodulators are under way. The cold-adapted live attenuated influenza virus vaccines for nasal administration are nearing availability. They are safe, immunogenic, and protective with greatest effectiveness among young children, in whom inactivated vaccines are less useful. Use among children should moderate the high frequencies of illness and hospitalization in this group and reduce spread of influenza in the community. CRV also provide an alternative to inactivated vaccines among young adults, in whom they can be equally protective.

Animals↗
PubMed1993

Diminished influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte activity among elderly persons.

Influenza A virus-specific MHC class I-restricted cytotoxic T lymphocyte (CTL) activities among young and elderly adults were compared. Peripheral blood lymphocytes from 10 young adults, (mean age 27 +/- 2.4 years) and elderly persons (mean age 71 +/- 1.6 years) were stimulated with influenza A/Taiwan/1/86 (H1N1) virus for 7 days and assayed for lytic activity against A/Taiwan, A/Shanghai (H3N2), and B/USSR virus-infected autologous target cells. Young adults exhibited significantly higher influenza A cross-reactive CTL activity against A/H1N1 and A/H3N2 target cells when compared to aged persons. This was true at all effector-to-target cell ratios tested. Negligible lysis of B/USSR-infected target cells or nonautologous A/Taiwan-infected cells was observed. The number of leukocytes recovered per milliliter of blood was also significantly higher in young adults than in old donors; however, the percentage of CD45+ (common leukocyte antigen), CD3+ (T cells), CD4+ (T helper), and CD8+ (T cytotoxic/suppressor) as well as the CD4+/CD8+ ratios was similar in both groups. Depletion of cells with monoclonal antibodies indicated that the effector cells were CD8+ T cells. Serum-neutralizing antibody (Nt Ab) titers were similar among young and elderly persons and there was no correlation between Nt Ab and CTL activity. These results demonstrate a reduced influenza virus-specific MHC class I-restricted CTL activity among elderly persons. The deficiency in this cell-mediated immune function may contribute to the morbidity and mortality from influenza virus infections in this population.

Adult↗
PubMed1993

Trivalent attenuated cold-adapted influenza virus vaccine: reduced viral shedding and serum antibody responses in susceptible adults.

Trivalent cold-adapted recombinant (CR) influenza virus vaccines containing types A (H1N1 and H3N2) and B viruses were evaluated in two double-blind, placebo-controlled trials. Susceptible adults were randomly assigned to receive the following vaccines by intranasal drops 1 month apart: two doses of trivalent vaccine, bivalent CR influenza A (Bi A) vaccine followed by monovalent B (Mono B) vaccine or vice versa, or two doses of placebo. All vaccines were well tolerated. Shedding of each of the three vaccine viruses was reduced after the first dose of trivalent vaccine compared with primary vaccination with Bi A or Mono B. Shedding was also reduced after second vaccinations, whether homologous (trivalent-trivalent) or heterologous (Bi A/Mono B or Mono B/Bi A). Reduced viral shedding was associated with reduced serum antibody responses. Thus, both simultaneous and sequential inoculations of susceptible adults with CR influenza vaccine viruses result in reduced viral shedding and serum antibody responses.

Administration, Intranasal↗
PubMed1993

Comparison of rapid diagnostic techniques for respiratory syncytial and influenza A virus respiratory infections in young children.

We performed virus isolation tests for respiratory viruses on combined nasal wash-throat swab specimens collected from infants and children with acute respiratory illnesses presenting to a hospital clinic during a 3-month period of concurrent epidemics of respiratory syncytial virus (RSV) and influenza A virus (Flu A) infections. Virus isolation results were used to assess the utility of commercially available rapid diagnostic kits for these two viruses. The kits employed direct immunofluorescence (IF) of cells (Imagen for RSV and Flu A), indirect IF of cells (Baxter Bartels Microscan), and enzyme immunoassay (EIA) (Becton Dickinson Directigen for RSV and Flu A and Abbott TestPack for RSV). All testing was completed on 81 specimens from 80 subjects. Of the 81 specimens, 53 (65%) yielded a virus: RSV, 28%; Flu A, 25%; rhinovirus, 6%; and enterovirus, cytomegalovirus, herpes simplex virus, and adenovirus, 2 to 4% each. Among the tests, Bartels Microscan and Directigen Flu-A exhibited the highest sensitivities (87 and 75%) and efficiencies (94 and 94%) for RSV and Flu A, respectively. All the tests exhibited high specificity. Thus, optimal detection of RSV and Flu A among infants and children who presented to a hospital clinic required two different detection methods (IF and enzyme immunoassay) and kits from two different companies (Baxter [Bartels Microscan] and Becton Dickinson [Directigen]).

Child↗
PubMed1991

Age distribution of patients with medically-attended illnesses caused by sequential variants of influenza A/H1N1: comparison to age-specific infection rates, 1978-1989.

Since influenza A/H1N1 viruses reappeared during the 1977-1978 season, this subtype has contributed 27% of 6,609 documented influenza infections of persons with acute respiratory disease presenting to clinics serving as surveillance sites of the Influenza Research Center in Houston for the 12-year period ending June 1989. Wide differences in the distribution of H1N1 viruses occurred by age group: more than 50% of H1N1 infections were detected among persons aged 10-34 years, compared with 28% for influenza A/H3N2 and 35% for influenza B. Over age 35 years, the contribution of H1N1 viruses dropped to only 4%, compared with 20% and 16% for influenza A/H3N2 and influenza B, respectively. When birth dates of persons with positive cultures were examined, it was found that most of the H1N1-positive persons were born after 1950. Concurrently, longitudinal studies of families and other adults under intensive surveillance for infection, including cultures of all respiratory illnesses and tests for serum antibody rise over the respiratory disease season, revealed appreciable infection rates for adults born before 1950. Furthermore, the annual peak of hospitalization of older persons with pneumonia and other acute respiratory illnesses was significantly correlated with the peak of H1N1 virus activity in 1978-1979, a year when H1N1 viruses were the only influenza viruses prevalent. These observations indicate that many persons infected with influenza A/H1N1 viruses that circulated from 1946 through 1953 have immunity which has persisted for more than 25 years but this immunity is not complete. Reinfection that may result in serious illness in older vulnerable adults does occur but with lower frequency than with influenza A/H3N2 infection. Currently prevalent H1N1 variants are antigenically different from those that circulated in the 1950s; however, older adults readily acquire immunity to these new variants--perhaps as a result of immunologic priming that occurred in childhood.

Acute Disease↗