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Biomedical subjects

R B Belshe

Publications and source records attributed to R B Belshe.

At least 91 records · Page 5Linked to original sources
PubMed1992

Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network.

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.

AIDS Vaccines↗
PubMed1992

Detection of binding antibodies to native and recombinant human immunodeficiency virus type 1 envelope glycoproteins following recombinant gp160 immunization measured by flow cytometry and enzyme immunoassays. The AIDS Vaccine Clinical Trials Network.

The ability of antibody induced by vaccination with recombinant gp160 (rgp160) to bind to native and recombinant human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins was measured. Thirty-three HIV-1-seronegative healthy adult volunteers were injected four times with 40 or 80 micrograms of an HIV-1LAV envelope glycoprotein candidate vaccine per dose. The vaccine consisted of rgp160 produced in insect tissue culture cells infected with a recombinant baculovirus which contains the gp160 gene from the HIV-1LAV strain. By using a flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to native envelope glycoprotein expressed by target cells infected with HIV-1IIIB, sera from 9 of the 33 vaccinees were positive. These included sera from eight vaccinees which stained HIV-1IIIB-infected cells and sera from two vaccinees which stained target cells infected with HIV-1MN, a heterologous virus strain. None of the sera stained cells infected with the HIV-1RF strain. Envelope glycoprotein-binding antibody was more frequently detectable in an enzyme-linked immunosorbent assay (ELISA) by using rgp160 compared with that which was detectable in the FIFA with uninfected target cells which were pulsed with rgp160 antigen. Positive correlations were observed between the rgp160 FIFA and a whole-virus-lysate enzyme immunoassay, between the rgp160 FIFA and the rgp160 ELISA, and between the rgp160 ELISA and the whole-virus-lysate enzyme immunoassay. The ability of sera from some volunteers who received rgp160 vaccine to bind to HIV-1-infected cells suggests that further studies with this vaccine should be done.

AIDS Vaccines↗
PubMed1992

Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children.

Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccine to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine.

Adaptation, Physiological↗
PubMed1992

Evaluation of a cold-adapted influenza B/Texas/84 reassortant virus (CRB-87) vaccine in young children.

A cold-adapted (ca) influenza B reassortant virus vaccine that contained the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus and the neuraminidase and hemagglutinin genes from wild-type influenza B/Texas/1/84 virus was evaluated in children ranging in age from 8 months to 14 years. The children were vaccinated intranasally with doses ranging from 10(3.2) to 10(6.2) 50% tissue culture infective doses (TCID50). Thirty children were seropositive, and 26 were seronegative. Thirty-three children participated as unvaccinated controls. The vaccine was well tolerated by both seronegative and seropositive children. The amount of virus required to infect 50% of seronegative children was approximately 10(4.5) TCID50. Vaccine viruses recovered from airway secretions retained temperature-sensitive and cold-adapted characteristics. The results of this study indicate that the vaccine virus, influenza B/Texas/84 ca reassortant virus, is attenuated, immunogenic, and phenotypically stable when given to young seronegative children.

Adaptation, Biological↗
PubMed1991

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network.

OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans. SUBJECTS: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups. INTERVENTIONS: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540. MEASUREMENTS AND MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time. CONCLUSIONS: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.

Adult↗
PubMed1991

Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine.

The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two randomized, double-blind, placebo-controlled trials involving patients with laboratory-documented influenza A virus (H3N2 subtype) illness of 2 days' duration or less. In a family-based study, rimantadine treatment for 10 days (24 children and adults) was associated with significant decreases in the number of days to a 50% reduction in symptoms (mean difference, 2.5 days), days of fever (1.6 days), and days of restricted activity (1.5 days) compared with the results obtained with placebo-treated patients (32 children and adults). Drug-resistant virus was recovered from eight (33%) of the rimantadine recipients on day 5. No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not. Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not. In a study of adults treated for 5 days (six treated with rimantadine, six treated with placebo), resistant virus was recovered in three rimantadine recipients by day 3 of treatment. The results indicate that drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment, but that rimantadine retains a net therapeutic benefit compared with that of placebo.

Adolescent↗
PubMed1991

A single-season epidemic with respiratory syncytial virus subgroup B2 during 10 epidemic years, 1978 to 1988.

Respiratory syncytial virus strains isolated from infants and children hospitalized with acute respiratory tract disease in Huntington, W. Va., from July 1979 through June 1988 were categorized by subgroup by using two panels of monoclonal antibodies specific for subgroup A and subgroup B. Of 405 strains tested, 319 (78.8%) were subgroup A, 73 (18.0%) were subgroup B1, and 13 (3.2%) were subgroup B2. The subgroup B2 strains occurred as a single-season epidemic during the epidemiologic year July 1980 to June 1981, except for one strain isolated in the epidemiologic year 1978 to 1979. Subgroup B strains were associated with significantly fewer bronchiolitis illnesses than subgroup A strains. The severity of illnesses caused by subgroup B1 and B2 strains was the same.

Age Factors↗
PubMed1991

Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees.

In an attempt to evaluate the level of attenuation of live parainfluenza type 3 virus (PIV3) vaccine candidates, we compared the responses of partially immune adult volunteers inoculated intranasally with 10(6) to 10(7) 50% tissue culture infective dose (TCID50) of bovine PIV3 (n = 18) or cold-adapted (ca) PIV3 (n = 37) with those of 28 adults administered 10(6) to 10(7) TCID50 of wild-type PIV3. The candidate vaccine viruses and the wild-type virus were avirulent and poorly infectious for these adults even though all of them had a low level of nasal antibodies to PIV3. To determine whether the ca PIV3 was attenuated, we then administered 10(4) TCID50 of ca PIV3 (cold-passage 12) or wild-type PIV3 intranasally and intratracheally to two fully susceptible chimpanzees, respectively, and challenged the four primates with wild-type virus 1 month later. Compared with wild-type virus, which caused upper respiratory tract illness, the ca PIV3 was highly attenuated and manifested a 500-fold reduction in virus replication in both the upper and lower respiratory tracts of the two immunized animals. Despite restriction of virus replication, infection with ca PIV3 conferred a high level of protective immunity against challenge with wild-type virus. The ca PIV3 which had been passaged 12 times at 20 degrees C did not retain its ts phenotype. These findings indicate that ca PIV3 may be a promising vaccine candidate for human beings if a passage level can be identified that is genetically stable, satisfactorily attenuated, and immunogenic.

Adaptation, Physiological↗
PubMed1991

Superiority of live attenuated compared with inactivated influenza A virus vaccines in older, chronically ill adults.

Forty-eight older adults with chronic diseases were vaccinated intranasally with live attenuated influenza A/Korea/1/82 (H3N2), CR59 virus. Forty-two (88 percent) CR59 virus recipients became infected with vaccine virus without adverse effects or change in mean pulmonary function even among the 29 infected recipients with moderate to severe chronic obstructive pulmonary disease. Among control groups who received either monovalent or trivalent inactivated influenza virus vaccines intramuscularly, the rates of fourfold rises in serum antibody titer to hemagglutinin (HA) were not different from the rate following CR59 virus inoculation. However, CR59 virus was superior to inactivated virus vaccine at stimulating secretory antibody to HA. Vaccinees age 65 years and older were more likely to shed CR59 virus in nasal secretions than were younger vaccinees, but antibody responses were not different. CR59 virus vaccine was safe and immunogenic in this population and more often induced a nasal wash IgA antibody response than the inactivated virus vaccines.

Administration, Intranasal↗
PubMed1991

Enhanced lymphoproliferation to influenza A virus following vaccination of older, chronically ill adults with live-attenuated viruses.

To question whether cellular immunity was stimulated by live-attenuated viruses in older, chronically ill adults, we intranasally inoculated 2 groups of volunteers (n = 37) with 2 different cold-recombinant, live-attenuated influenza A virus vaccines, and measured peripheral blood mononuclear cell responsiveness to influenza antigens and mitogen before and after vaccination. Lymphocyte proliferation to vaccine virus and to heterosubtypic influenza A virus increased postvaccination even in the subpopulation of vaccines who had a 4-fold nasal wash antibody titer rise to vaccine virus hemagglutinin, but no concomitant serum antibody titer rise to hemagglutinin. Vaccines aged greater than or equal to 65 years exhibited a rise in proliferation to vaccine virus postvaccination, as well. Based on lymphocyte proliferation, vaccine virus infection induced an enhanced cell-mediated immune response. Higher prevaccination serum antibody titers, however, were associated with protection from vaccine virus infection, and higher lymphocyte proliferation was not.

Aged↗
PubMed1990

Palmitoylation of the influenza A virus M2 protein.

The M2 proteins of a variety of influenza A viruses of different subtypes were shown to possess associated palmitate. Susceptibility to removal by reduction or treatment with hydroxylamine is consistent with attachment via a thioester linkage to cysteine. The absence of the acyl group from the M2 proteins of several equine viruses of the H3N8 subtype correlates with the replacement of cysteine 50 with phenylalanine and points to this as the site of palmitate attachment.

Amino Acid Sequence↗
PubMed1990

Synthesis and antiviral activity of metabolites of rimantadine.

The hydroxy metabolites of rimantadine (3-5) were synthesized and compared to amantadine (1) and rimantadine (2) for their ability to inhibit the replication of influenza viruses in vitro. All three metabolites were inhibitory to wild-type influenza A viruses (H3N2 and H1N1). In particular, 2-hydroxyrimantadine (3) showed similar activity to amantadine, but the 3- and 4-hydroxy metabolites (4 and 5, respectively), both of which are found in rimantadine-treated patients, showed only modest inhibitory activity. A rimantadine-resistant isolate of influenza A virus exhibited cross-resistance to amantadine and to each of the metabolites 3-5. None of the compounds were effective against influenza B virus.

Adamantane↗
PubMed1990

Guinea pig model for antibiotic transport across gastric mucosa: inhibitory tissue concentrations of clindamycin against Helicobacter pylori (Campylobacter pylori) following two separate dose regimens.

An animal model for antibiotic secretion across gastric mucosa was developed using adult guinea pigs. Antibiotics were given intramuscularly, and levels in serum and gastric mucosa were measured by high-pressure liquid chromatography at 1, 2, 4, 6, and 8 h postinjection. Mucosal levels of the drugs were measured in the superficial luminal portion of the mucosa, which was removed by mechanical scraping. Clindamycin levels were measured after doses of 10 and 100 mg/kg of body weight. After doses of 100 mg/kg, levels in serum peaked at 15.95 micrograms/ml at 2 h. Gastric mucosa showed a bimodal concentration curve with peaks of 15.91 micrograms/g at 1 h and 25.07 micrograms/g at 4 h. Concentrations in mucosa remained high when levels in serum fell, showing a mucosa/serum ratio of 87.70 after 8 h. At all times, clindamycin levels in mucosa were in excess of the MIC for 90% of the Helicobacter (Campylobacter) pylori strains tested.

Anti-Bacterial Agents↗
PubMed1990

Enhancement of anti-influenza A virus cytotoxicity following influenza A virus vaccination in older, chronically ill adults.

We studied anti-influenza cytotoxicity by bulk peripheral blood mononuclear leukocyte (PBL) cultures derived from older, chronically ill volunteers undergoing vaccination. Vaccinees received either cold-recombinant, live-attenuated influenza A/Korea/1/82 (H3N2) virus intranasally or inactivated monovalent influenza A/Taiwan/1/86 (H1N1) subvirion vaccine intramuscularly. PBL were collected pre- and postvaccination and in vitro stimulated by autologous PBL infected with influenza A virus homologous and heterosubtypic to the respective vaccine strain. Cytotoxicity was measured against influenza A virus-infected autologous and human leukocyte antigen (HLA)-mismatched PBL targets infected with influenza A virus homologous or heterosubtypic to the vaccine virus strain. Vaccinees infected with the live-attenuated virus developed significant rises in mean anti-influenza, HLA-restricted cytotoxicity that was cross-reactive against influenza A viruses homologous and heterosubtypic to the vaccine virus. The enhanced cross-reactive cytotoxicity was inducible postvaccination by in vitro stimulation with autologous PBL infected with the homologous influenza A (H3N2) virus and with influenza A (H1N1) virus. In contrast, after vaccination with inactivated monovalent subvirion vaccine, volunteers developed significant increases in mean anti-influenza, HLA-restricted cytotoxicity only against autologous PBL infected with homologous influenza A (H1N1) virus. Increased cytotoxicity occurred only after in vitro stimulation with autologous cells infected with homologous influenza A (H1N1) virus. Mean gamma interferon levels in supernatant fluids of influenza A virus-stimulated effector PBL did not increase postvaccination, despite increased levels of anti-influenza cytotoxicity displayed by the effector cells. We conclude that the live-attenuated influenza A virus infection induced a broader range of enhanced anti-influenza cytotoxicity than did the inactivated subvirion vaccine.

Aged↗
PubMed1990

Characteristics of a population volunteering for human immunodeficiency virus immunization. NIAID AIDS Clinical Trials Network.

A total of 166 volunteers for an AIDS vaccine study (Vaxsyn, baculovirus produced recombinant GP160; MicroGeneSys Inc, West Haven, Connecticut, USA) were interviewed and examined. Blood was collected for routine laboratory testing as well as T-cell counts, HIV ELISA (EIA), Western blot (WB) and p24 Ag. Eighty-five men (mean age 22.2 years, range 18-42) and 81 women (mean age 23.9 years, range 17-50) volunteered; 130/166 (78%) were university students. Most had learned of the study from news media (55%), friends or workplace (37%). The most common causes for exclusion were the presence of indeterminate WB (26.5%) or a change of mind after the initial interview (24%). Other causes were abnormal cell count and differential (7.2%), elevated alanine aminotransferase (3.6%), positive hepatitis B antibody (3.6%), abnormal urinalysis (3.4%), recent venereal disease (3.0%), T4 cell count less than 400 (1.9%), abnormal chest X-ray (1.7%), recognized high-risk behaviour (1.7%), multiple sex partners (1.2%), positive rapid plasma reagin test (1.2%), failure to meet age criteria (1.2%), unable to be available for entire study (1.2%), abnormal physical examination (0.6%) and positive p24 Ag (0.6%). No volunteers had positive EIA, but 14.5% had more than one reason for exclusion. Even in a community with low prevalence for HIV, a large majority of healthy heterosexual volunteers can be expected to be ineligible for enrollment in HIV vaccine trials. An average of 4.8 volunteers were screened for each of 12 vaccinees chosen.

AIDS Vaccines↗
PubMed1990

Occurrence, characteristics, and patterns of HIV-1 and HIV-2 western blot indeterminate sera in low risk populations in West Virginia and pre-AIDS Africa.

To further characterize HIV-1 and HIV-2 Western blot indeterminate (IWB) sera, 402 sera from 318 healthy low-risk individuals from West Virginia and 159 African sera obtained in the pre-AIDS era (1968-1972) were studied. All IWB sera tested for antigen by HIV-1 enzyme immunoassay (EIA-Ag) were negative. HIV-1 and HIV-2 IWB reactivity occurred independent of HIV-1 and HIV-2 false-positive testing for antibody by enzyme immunoassay (EIA-Ab) and no cross-reactions between HIV-1 and HIV-2 IWB patterns were detected. The IWB patterns were reproducible, demonstrated no age or sex related pattern, and showed no evidence of vertical or horizontal transmission. The African sera exhibited a significantly higher number of IWB patterns. IWB reactivity in HIV-1 and HIV-2 seronegative individuals may not be viral in origin and the occurrence of IWB pattern may vary among populations.

Adolescent↗
PubMed1989

Emergence and apparent transmission of rimantadine-resistant influenza A virus in families.

To determine whether rimantadine can protect family members from acquiring influenza A viral illness and to assess the possible selection of drug-resistant strains of virus, we conducted a randomized, double-blind, placebo-controlled study in three communities during two influenza seasons. When influenza A occurred in a family, the members (including the index patient) were given either rimantadine (adult oral dose, 200 mg per day) or placebo for 10 days. The presence of illness was monitored by daily recording of symptoms and temperature measurements; infection was determined by isolation of the virus and by serologic studies. Among households with documented influenza A infections, symptomatic illness occurred in one or more contacts in 10 of 28 families treated with rimantadine and in 10 of 209 families treated with placebo. Asymptomatic secondary influenza A infections were found in five families assigned to receive rimantadine and in four families assigned to receive placebo. Rimantadine-resistant strains of influenza A virus (H3N2 subtype) with mutations consisting of single amino acid changes in the M2 protein (residue 27, 30, or 31) were recovered from eight index patients and five contacts treated with rimantadine. There was apparent transmission of drug-resistant strains of virus in six contacts with secondary illnesses in five families. We conclude that when index patients are treated concurrently, rimantadine is ineffective in protecting household members from influenza A infection. If rimantadine is used for both treatment and postexposure prophylaxis in families, rapid selection and apparent transmission of drug-resistant influenza A viruses can occur.

Adamantane↗