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Biomedical subjects

R B Belshe

Publications and source records attributed to R B Belshe.

At least 55 records · Page 3Linked to original sources
PubMed1996

Immune responses stimulated by percutaneous and intradermal bacille Calmette-Guérin.

Healthy volunteers were randomized to receive percutaneous or intradermal bacille Calmette-Guérin (BCG) vaccination. Delayed-type hypersensitivity (DTH) to tuberculin, as well as proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated by whole cell lysates and culture filtrates of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare, were compared before and after vaccination. Positive DTH reactions were detected in 83% of intradermal and 40% of percutaneous BCG recipients 3 months after vaccination (P < .004). M. tuberculosis-specific proliferation was increased after intradermal BCG (P < .01) but not after percutaneous BCG compared with prevaccination responses. In addition, M. tuberculosis-specific interferon-gamma production was increased after intradermal BCG compared with both prevaccination responses (P < .04) and those measured after percutaneous BCG (P < .05). Predominant immune responses stimulated by BCG were directed against antigens present in mycobacterial whole cell lysate. These results indicate that the BCG vaccination route can affect both in vivo and in vitro immune responses.

Administration, Cutaneous↗
PubMed1996

Antibody to native human immunodeficiency virus type 1 envelope glycoproteins induced by IIIB and MN recombinant gp120 vaccines. The NIAID AIDS Vaccine Evaluation Group.

The ability of antibody induced by MN and IIIB recombinant gp120 (rgp120) human immunodeficiency virus type 1 (HIV-1) vaccines the bind to oligomeric native and monomeric recombinant HIV-1 envelope glycoproteins (rgp 120) was measured in 25 uninfected, healthy adult volunteers. A major focus was to evaluate the effect of simultaneous and sequential immunization with vaccines representing different strains of HIV-1 on the ability to broaden cross-reactivity of antibodies against these and other HIV-1 strains. A flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to envelope glycoprotein expressed by infected and rgp120-coated target cells was used, MN rgp120 HIV-1 vaccine given alone and coadministered with IIIB rgp120 HIV-1 vaccine elicited antibody which bound to cells infected with HIV-1MN, HIV-IIIB, HIV-1RF, and HIV-1-SF2. The presence of envelope glycoprotein-binding antibody detected by FIFA correlated to a moderate degree with functional antibody against HIV-1MN and HIV-IIIB. Priming immunization with IIIB rgp120 HIV-1 vaccine followed by booster injections of MN rgp120 HIV-1 vaccine resulted in increased cross-reactive antibody binding to these and heterologous clade B HIV-1 strains infecting cells. MN rgp120 HIV-1 vaccine given alone was better able to induce cross-reactive antibody to cells infected with heterologous HIV-1 laboratory strains than was IIIB rgp120 HIV-1 vaccine given alone. The vaccines induced binding antibody to rgp120 possessing the amino acid sequence of a clade E HIV-1 strain as measured by enzyme-linked immunosorbent assay. Levels of antibody binding to cells infected with clade B HIV-1 and cells coated with monomeric rgp120 were greater than that induced by HIV-1IIIB-based gp160 vaccines in previous studies.

AIDS Vaccines↗
PubMed1996

Salivary binding antibodies induced by human immunodeficiency virus type 1 recombinant gp120 vaccine. The NIAID AIDS Vaccine Evaluation Group.

Salivary binding antibodies induced by candidate human immunodeficiency virus type 1 (HIV-1) vaccines in healthy, HIV-1 uninfected volunteers were assessed in a clinical trial evaluating intramuscularly injected HIV-1MN recombinant gp120 (rgp120) vaccine alone or with HIV-1IIIB rgp120 vaccine. The two rgp120 vaccines induced envelope glycoprotein-specific immunoglobulin G (IgG) and IgA antibodies in whole saliva and serum.

AIDS Vaccines↗
PubMed1996

Temperature-sensitive phenotype of the human parainfluenza virus type 3 candidate vaccine strain (cp45) correlates with a defect in the L gene.

We have previously demonstrated that the temperature sensitivity of a human parainfluenza virus type 3 (HPIV-3) candidate vaccine strain (cp45), which is currently under evaluation in humans, is associated with poor transcriptional activity of the virus at the nonpermissive temperature (R. Ray, K. Meyer, F. Newman, and R. B. Belshe, J. Virol. 69:1959-1963, 1995). In this study, the temperature sensitivity of cp45 virus was further investigated by the complementation of a specific gene function. CV-1 cells were transfected with cloned genes from wild-type HPIV-3 encoding the large protein (L), phosphoprotein (P), and nucleocapsid protein (NP), alone or together, for the expression of biologically active proteins. Only cells expressing the L gene were able to rescue cp45 replication when incubated at the nonpermissive temperature (39.5 degrees C), whereas cells transiently expressing NP or P were incapable of rescuing the virus. The virus titers obtained following complementation of the L protein were 190 to 2,300 PFU/ml of culture medium, compared with the undetectable growth of the cp45 temperature-sensitive mutant at the nonpermissive temperature. Rescued progeny virus still maintained the temperature-sensitive phenotype. Results from this study suggest that the temperature sensitivity of the cp45 candidate vaccine strain is associated primarily with L-protein function and that the defect can be complemented by transient expression of the wild-type protein. This study underscores the importance of the L protein in RNA polymerase activity and its critical role in virus replication.

Animals↗
PubMed1995

Interchangeability of conjugated Haemophilus influenzae type b vaccines in infants.

OBJECTIVE: To evaluate the safety and immunogenicity of two Haemophilus influenzae type b (Hib) conjugate vaccines when administered in serial combination. These vaccines consisted of Hib capsular polysaccharide polyribosyl-ribitol phosphate (PRP) conjugated to the meningococcal outer membrane protein (OMP) complex (PRP-OMP) and H influenzae oligosaccharide conjugated to a mutant toxin (CRM197) isolated from Corynebacterium diphtheriae (HbOC). DESIGN: Randomized, double-blind, clinical trial evaluating five Hib vaccination regimens. SETTING: Vaccine Treatment and Evaluation Units and affiliated private pediatric practices at Saint Louis (Mo) University, Vanderbilt University, Nashville, Tenn, and Baylor College of Medicine, Houston, Tex. PATIENTS: A total of 497 healthy 2-month-old infants scheduled to receive routine immunization. INTERVENTION: Participants received either PRP-OMP or HbOC given as recommended by the manufacturer, PRP-OMP at 2 and 6 months, HbOC at 2 months, then PRP-OMP at 4 and 6 months, or PRP-OMP at 2 months and then HbOC at 4 and 6 months. Unconjugated PRP was given at 15 months to evaluate priming. RESULTS: Geometric mean antibody concentrations differed significantly among the groups following the second and third immunizations of the primary series and following booster immunization with unconjugated PRP. On each occasion, the groups receiving serial combinations of PRP-OMP and HbOC achieved mean antibody concentrations that equalled or exceeded those of the groups receiving a single product. Adverse reactions did not vary by group. CONCLUSIONS: The studied sequential combinations of Hib vaccines were safe and at least as immunogenic as either vaccine alone.

Antibodies, Bacterial↗
PubMed1995

Recombinant gp160 vaccination schedule and MHC HLA type as factors influencing cellular responses to HIV-1 envelope glycoprotein. NIAID AIDS Vaccine Clinical Trials Network.

This study assessed (1) T-cell responses following vaccination of HIV-1 negative volunteers with HIV-1LAI recombinant gp160 (rgp160) vaccine, and (2) effects of vaccine injection schedule and MHC HLA type on those responses. In one trial, volunteers received rgp160 in two accelerated schedules (Groups 1 and 2). In the other trial, volunteers received rgp160 vaccine at 0, 1, 6, and 12 months and some received vaccine at 18 months (Groups 3 and 4). Peripheral blood mononuclear cells (PBMC) from vaccinees in Groups 3 and 4 were stimulated by more peptides representing envelope glycoprotein T-cell epitopes than Groups 1 and 2 (p = 0.01). Transient anti-envelope glycoprotein CTL activity was more frequently detectable in Groups 1 and 2 (p = 0.03). MHC HLA-Cw7, DR1 and DQw1 alleles appeared to be associated with PBMC responses to envelope glycoprotein.

AIDS Vaccines↗
PubMed1995

HIV-1 recombinant gp160 vaccine induced antibodies in serum and saliva. The NIAID AIDS Vaccine Clinical Trials Network.

As part of a phase I safety and immunogenicity trial of a vaccinia-expressed HIV-1 recombinant gp160 (rgp160) candidate vaccine, we measured serum and saliva antibody responses in low risk, uninfected volunteers. Six healthy adult volunteers received 50 micrograms doses of rgp160 vaccine adjuvanted in alum and deoxycholate at months 0, 1, 6, and 12. A 200 micrograms rgp160 immunization was given to four volunteers at 18 months. The vaccine induced anti-envelope glycoprotein IgG and IgA serum antibodies in all six volunteers. Saliva antibodies to envelope glycoprotein appeared in some volunteers at certain timepoints. Three volunteers appeared to transiently develop vaccine-induced secretory IgA antibody to envelope glycoprotein in whole saliva.

AIDS Vaccines↗
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

Characterization of a live, attenuated human parainfluenza type 3 virus candidate vaccine strain.

Characterization of a temperature-sensitive and live, attenuated human parainfluenza type 3 virus strain (cp45) grown at a permissive temperature (32 degrees C) suggested that the virus efficiently multiplies in cell lines and retains antigenic and functional properties of the envelope glycoproteins. When grown at a nonpermissive temperature (39.5 degrees C), the cp45 virus exhibited poor replication; however, shifting to a permissive temperature allowed virus growth. Although at a nonpermissive temperature virus polypeptide synthesis was significantly reduced, the hemagglutinin-neuraminidase and fusion glycoproteins were transported to cell surfaces and retained their characteristic biologic activities. Studies on mRNA synthesis from the P protein gene suggested a poor transcriptional activity of the cp45 virus at a nonpermissive temperature. Results from this study indicate that the temperature sensitivity of cp45 virus is related to altered transcriptional activity and a marked reduction in virus polypeptide synthesis.

Antibodies, Monoclonal↗
PubMed1995

Immune responses to plasmid DNA encoding the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a major causative agent of parenterally transmitted non-A, non-B hepatitis. The genomic region encoding the virion-associated core protein is relatively conserved among HCV strains. To generate a DNA vaccine capable of expressing the HCV core protein, the genomic region encoding amino acid residues 1 to 191 of the HCV-1 strain was amplified and cloned into an eukaryotic expression vector. Intramuscular inoculation of recombinant plasmid DNA into BALB/c mice (H-2d) generated core-specific antibody responses, lymphoproliferative responses, and cytotoxic T-lymphocyte activity. Our results suggest that the HCV core polynucleotide warrants further investigation as a potential vaccine against HCV infection.

3T3 Cells↗
PubMed1994

Interpreting HIV serodiagnostic test results in the 1990s: social risks of HIV vaccine studies in uninfected volunteers. NIAID AIDS Vaccine Clinical Trials Group.

OBJECTIVE: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results. DESIGN: Retrospective cohort study. SETTING: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases. PARTICIPANTS: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection. MEASUREMENTS: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria. RESULTS: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected. CONCLUSIONS: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected.

AIDS Vaccines↗
PubMed1994

Effect of carrier protein priming on antibody responses to Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To assess the effect of priming with diphtheria and tetanus toxoid vaccine (DT) at 1 month of age on the anticapsular polyribosylribitol phosphate (PRP) antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate (PRP-T) or PRP oligosaccharide-cross-reactive mutant diphtheria toxin conjugate (HbOC). DESIGN: Randomized controlled trial with serum samples assayed blindly. PARTICIPANTS AND SETTING: Healthy infants enrolled in private pediatric practices; 94 (91%) of 103 infants had prevaccination and postvaccination serum samples available for analysis. INTERVENTIONS: Two groups received DT vaccination at 1 month of age and subsequent injections of PRP-T or HbOC conjugate vaccines at 2, 4, and 6 months of age. The control groups were not vaccinated with DT but received PRP-T or HbOC at the same ages as the carrier-primed groups. Infants in all groups were given a booster injection of unconjugated PRP at 12 months of age to assess induction of immunologic memory. MAIN OUTCOME MEASURE: Concentrations of serum antibody to PRP. MAIN RESULTS: The DT-primed infants given PRP-T had twofold to threefold higher geometric mean anti-PRP antibody responses after one (P < or = .01), two (P < or = .01), or three (P = .06) doses of conjugate vaccine than the infants of the unprimed group. The primed infants also had threefold higher memory antibody responses to the booster PRP injection given at 12 months of age (concentration of 24.4 vs 8.4 micrograms/mL in infants not primed with DT; P < .01). The DT-primed infants given HbOC had twofold to threefold higher antibody responses after one (P = .07) or two (P < .01) doses of conjugate vaccine than the unprimed HbOC group, but there were no significant differences after the third dose of conjugate vaccine or after the PRP booster injection. CONCLUSIONS: Vaccination with DT at 1 month of age increases the magnitude of the anti-PRP antibody responses to conjugate vaccination. With HbOC, the effect of carrier priming was present for up to 6 months of age, whereas in infants vaccinated with PRP-T, enhanced immunity was present for at least 12 months.

Antibodies, Bacterial↗
PubMed1994

Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. NIAID AIDS Vaccine Clinical Trials Network.

OBJECTIVE: To evaluate the safety and immunogenicity of the MN strain of recombinant gp120 (MN rgp120) as a vaccine prototype to prevent human immunodeficiency virus (HIV). DESIGN: Double-blind, randomized, placebo-controlled study with subjects vaccinated at 0, 4, 24, and 48 weeks and followed up through 64 weeks. SETTING: The AIDS Vaccine Evaluation Units in St Louis, Mo, Nashville, Tenn, and Rochester, NY, conducted the clinical study. Laboratory studies were conducted at Duke University, Raleigh, NC; data analysis was done by the Data Coordinating and Analysis Center at the EMMES Corporation, Potomac, Md. PARTICIPANTS: Fifty-seven persons seronegative for HIV, at low risk for acquiring HIV infection, and 18 to 60 years of age. INTERVENTIONS: The MN rgp120 vaccine was administered to 12 volunteers each in doses of 100 micrograms, 300 micrograms, or 600 micrograms, and 12 volunteers received a combination of 300 micrograms of MN rgp120 vaccine and 300 micrograms of vaccine from rgp120 of strain IIIB. Nine volunteers received alum adjuvant alone (control). MAIN OUTCOME MEASURES: Safety was assessed by monitoring lymphocyte subsets, serum creatinine, and liver enzymes. Immunogenicity was measured by enzyme-linked immunosorbent assay using the immunogen and synthetic peptide corresponding to the variable region 3 domain of gp120. Functional antibody assays included CD4 binding blocking; antibody-dependent, cell-mediated cytotoxicity; and neutralization of homologous and heterologous HIV strains. RESULTS: No severe adverse reactions occurred. In 33 of 48 volunteers, two doses of vaccine induced antibodies that neutralized the homologous strain HIV-1/MN. Three doses of vaccine induced antibodies that neutralized MN (in 46 of 48 volunteers), SF-2 (in 45 of 48 volunteers), or IIIB strains of HIV-1 (in 30 of 48 volunteers). CONCLUSION: The vaccines were safe and immunogenic. Multiple injections of vaccine broadened and increased the neutralizing antibody response.

AIDS Vaccines↗
PubMed1994

Acellular pertussis vaccines in infants: evaluation of single component and two-component products.

Two acellular pertussis vaccines, one containing only LPF toxoid (25 micrograms) and the other containing LPF toxoid (25 micrograms) and FHA (25 micrograms) and each combined with diphtheria and tetanus toxoids, were evaluated in two groups of 25 infants. A third group of 25 infants served as controls and received a DTP whole-cell pertussis vaccine. Infants given either acellular pertussis vaccine had significantly fewer local and systemic reactions than infants given whole-cell vaccine. Among the three vaccine groups, infants given the LPF vaccine (single component) had the highest concentration of antibody to LPF after three immunizations. Infants receiving the LPF/FHA vaccine (two-component) had the highest concentration of antibody to FHA after three immunizations. Infants vaccinated with the two-component vaccine had a significantly lower serological response to LPF than infants given the single component vaccine, as measured by either enzyme-linked immunosorbent assay or CHO cell assay. Further studies are necessary to determine why differences in immunogenicity of the two investigational vaccines occurred.

Antibodies, Bacterial↗
PubMed1994

Vaccine-induced antibodies to native and recombinant human immunodeficiency virus type 1 envelope glycoproteins. NIAID AIDS Vaccine Clinical Trials Network.

The ability of antibody induced by combination vaccination (human immunodeficiency virus type 1 (HIV-1LAV) gp160 live recombinant vaccinia virus priming followed by a booster injection with a baculovirus-expressed HIV-1LAV recombinant gp160 candidate vaccine) to bind to native and recombinant HIV-1 envelope glycoproteins was measured in 12 uninfected healthy adult volunteers. 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 (infected-cell FIFA), sera from ten of 12 vaccinees before the rgp160 booster injection were positive, and all vaccinees were positive at higher levels after the rgp160 boost. Evidence for cross-reacting antibody to HIV-1MN, HIV-1RF and HIV-1CC expressed on infected cells was also present after the rgp160 booster injection. High titres of anti-rgp160 antibody were also measured in an enzyme-linked immunosorbent assay after the boost. None of the sera obtained immediately prior to the rgp160 booster injection, but all sera drawn after the boost, reacted with recombinant gp160 antigen bound to uninfected cell surfaces. The high anti-gp160 binding activity in these assays, the concomitant presence of positivity in infected-cell and rgp160-coated cell FIFA assays, and high anti-rgp160 antibody titre by ELISA in sera from recipients of this prime-boost vaccination regimen suggest that the live vector priming and rgp160 boosting strategy should be pursued in HIV-1 vaccine development.

AIDS Vaccines↗
PubMed1994

Studies of high doses of a human immunodeficiency virus type 1 recombinant glycoprotein 160 candidate vaccine in HIV type 1-seronegative humans. The AIDS Vaccine Clinical Trials Network.

We examined the safety and immunogenicity of a baculovirus-derived recombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 micrograms to 56 healthy, HIV-1-seronegative adults, in a randomized, double-blind, placebo-controlled study. Immunizations were given intramuscularly at 0, 1, 6, and 12 months. Both doses were generally well tolerated, although self-limited local reactions were frequent. No other clinical or laboratory toxicities were noted, and no effects on CD4 or CD8 lymphocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WB) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 micrograms, respectively. Western blot responses developed more rapidly in the 640-micrograms group. High rates of EIA antibody responses to HIV-1 lysate were also present in both groups, and developed more rapidly in the 640-micrograms group. Enzyme immunoassay antibody responses to the immunogen (rgp160) were also frequent, but were infrequent to V3 to gp41 peptides. Neutralizing antibodies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subjects (GMT = 11) who received four doses of 160 micrograms, and in 10 of 19 subjects who received four doses of 640 micrograms (GMT = 32). Fusion inhibiting antibody was not detected. CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 micrograms. Complement-mediated antibody-dependent enhancement was found in sera from 11 of 19 volunteers in the 640-micrograms group. Lymphocyte proliferative responses to the immunogen were detected in 4 of 4 subjects tested, but no cytotoxic T cell activity was noted in 11 subjects. Administration of the 640-micrograms dose of this rgp160 vaccine candidate relative to the lower doses was associated with increased immunogenicity, including higher rates of homologous neutralizing antibody responses, although at low titer.

AIDS Vaccines↗