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Biomedical subjects

R B Belshe

Publications and source records attributed to R B Belshe.

At least 73 records · Page 4Linked to original sources
PubMed1994

Multidose, live attenuated, cold-recombinant, trivalent influenza vaccine in infants and young children.

Twenty-two healthy infants and children received either cold-recombinant, trivalent influenza vaccine or placebo in a three-dose vaccine trial. Most (82%) who received vaccine were seronegative to all three vaccine strains (10(6) TCID50/dose each): A/Kawasaki/9/86 (H1N1), A/Los Angeles/2/87 (H3N2), and B/Yamagata/16/88. Vaccine was administered intranasally at time 0 and 2 and 4 months later. The vaccine was well tolerated and immunogenic when administered in a multidose regimen. The first dose stimulated antibody to H1, H3, and B in 59%, 94%, and 35% of vaccinees, respectively, by hemagglutination inhibition (HAI) or ELISA. After two doses of vaccine, 93%, 93%, and 80% had antibody by HAI or ELISA to H1, H3, and B, respectively. Most vaccinees (67%) responded to all three viruses after two doses of vaccine. The third dose contributed little to the vaccine's immunogenicity. Multidose trivalent influenza vaccine is safe and induces an immune response in most vaccinees after two doses.

Dose-Response Relationship, Immunologic↗
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

Safety and immunogenicity of an inactivated hepatitis A vaccine: effect of dose and vaccination schedule.

The safety and immunogenicity of three doses (360 ELISA units [EU], 720 EU, and 1440 EU) and four immunization schedules (0, 1, and 2; 0, 1, and 6; 0, 1, and 12; 0, 2, and 4 months) of an inactivated hepatitis A vaccine were investigated in 80 healthy adult volunteers. Adverse effects were mild and comparable to those in a control group given hepatitis B vaccine. Antibody levels presumed to be protective (> or = 20 mIU/mL) were achieved after one injection in 90% of vaccinees given 360 and 720 EU and in 100% given 1440 EU. After two injections, 100% of vaccinees seroconverted regardless of the dose of vaccine given. All vaccine schedules were highly immunogenic. The accelerated and high-dose schedule could be useful for people who need to be rapidly immunized. The 12-month schedule induced very high levels of anti-hepatitis A virus but had problems with compliance. The 0-, 2-, and 4-month schedule produced higher antibody levels than the conventional 0-, 1-, and 6-month schedule (P = .016). This suggests that the hepatitis A vaccine could be incorporated into existing pediatric vaccine schedules.

Adolescent↗
PubMed1994

Determinants of antibody response after recombinant gp160 boosting in vaccinia-naive volunteers primed with gp160-recombinant vaccinia virus. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Clinical Trials Network.

Priming with a live recombinant vector followed by subunit boosting is a promising strategy for human immunodeficiency virus (HIV) immunization. Twenty-nine vaccinia-naive volunteers were primed with gp160-recombinant vaccinia virus (HIVAC-1e) and boosted with recombinant (r) gp160 to define factors associated with the magnitude and specificity of antibody response after booster immunization. A longer interval between inoculation and boost, two inoculations of HIVAC-1e with lesion formation occurring after the first, and Western blot-detectable antibody to gp160 after inoculation were significantly associated with higher neutralizing antibody titers and fusion-inhibiting activity after boosting. HIVAC-1e-primed vaccinees were more likely to have antibody to V3- and CD4-binding regions of gp120 and less likely to have antibody to constant regions 2 and 3 than vaccinees immunized with rgp160 alone. Priming volunteers with HIVAC-1e was a key determinant of the epitope specificity and magnitude of functional antibody responses induced by rgp160 boosting.

AIDS Vaccines↗
PubMed1994

Role of virion M2 protein in influenza virus uncoating: specific reduction in the rate of membrane fusion between virus and liposomes by amantadine.

The anti-influenza virus drug amantadine was shown to reduce the rate of fusion of liposomes with influenza A viruses whose replication is inhibited by this drug. The fusion with amantadine-resistant viruses was unaffected. Experiments with reassortant and mutant viruses showed that this effect was linked to the M2 protein and not to the haemagglutinin of the virus. The proton ionophore monensin, on the other hand, substantially increased the rate of fusion of the viruses tested. These results indicate that the kinetics of virus-liposome fusion can be modulated by the virus M2 protein, the target of amantadine action, and it is postulated that the M2 ion channel functions by transporting protons into the virion interior and facilitating virus uncoating.

Amantadine↗
PubMed1994

HIV-1 recombinant gp160 vaccine given in accelerated dose schedules. NIAID AIDS Vaccine Clinical Trials Network.

The purpose of this randomized, double-blind study was to test the safety and immunogenicity of an HIV-1LAI recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned to receive 50-micrograms doses of rgp160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months; and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12-18 months in other studies.

AIDS Vaccines↗
PubMed1994

Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults.

A meningococcal vaccine containing group A and C polysaccharides conjugated to CRM197 was evaluated in 50 adults. Vaccinees were entered into one of five groups: 30 adults received a single dose of either 22, 11, or 5.5 micrograms of the conjugated A-C vaccine; 10 received an approved meningococcal vaccine; and 10 received saline injections. Local and systemic reactions to vaccines were recorded, and immune responses were determined. The experimental meningococcal vaccine was well tolerated, with the most frequent reaction being pain at the injection site. Both A and C polysaccharide components of the experimental vaccine were highly immunogenic, and total antibody concentrations 1 month postvaccination were not significantly different from the mean antibody concentrations among adults given the approved meningococcal vaccine. In addition, significant rises in immunoglobulin G, A, and M antibodies to both A and C polysaccharides occurred. Antibody concentrations measured at 6 and 12 months postvaccination had declined but remained significantly higher than prevaccination concentrations. Postvaccination meningococcal group C functional antibody activity increased more than 600-fold for both the polysaccharide and the conjugate vaccines. Further studies of this conjugated meningococcal vaccine are indicated for young children and infants.

Adolescent↗
PubMed1994

Rapid detection of parainfluenza virus type 3 RNA in respiratory specimens: use of reverse transcription-PCR-enzyme immunoassay.

Parainfluenza virus type 3 (PIV-3), an important lower respiratory tract pathogen in young children and immunocompromised individuals, may be underdiagnosed because of the insensitivity of available culturing systems and delay in identification of virus in cell culture. We developed a reverse transcription-PCR-enzyme immunoassay (RT-PCR-EIA) for PIV-3, using primers specific for a highly conserved region of the hemagglutinin-neuraminidase gene. Testing of nasal washes spiked with PIV-3 or other respiratory viruses showed that this assay detected seven strains of PIV-3 but not other respiratory viruses. Of 103 respiratory tract samples obtained from children experimentally infected with a liver PIV-3 vaccine or naturally infected with wild-type PIV-3, 51 were positive by culture and 48 were positive by RT-PCR-EIA. Eleven of the culture-positive samples were negative by RT-PCR-EIA; however, none of these grew virus upon reinoculation into cell culture, indicating that virus was lost or was present at a very low titer. Eight of the culture-negative samples were positive by RT-PCR-EIA: two were obtained from a subject who was culture negative but had a serologic response to PIV-3, four were obtained 7 to 9 days after the first positive culture, and two were obtained 1 day prior to the first positive culture. Thus, this RT-PCR-EIA for PIV-3 is sensitive and specific and can detect viral RNA in samples from which virus cannot be cultivated. This assay could be used for diagnosis late in the course of PIV-3 infection and for accurate detection of disease outbreaks.

Base Sequence↗
PubMed1993

Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. The NIAID AIDS Vaccine Clinical Trials Network.

Twelve vaccinia-naive volunteers were inoculated with recombinant vaccinia virus expressing the human immunodeficiency virus type 1 (HIV-1) strain IIIB (HIV-1IIIB) envelope glycoprotein gp160 and subsequently immunized with 640 micrograms of recombinant (r) gp160 protein produced in baculovirus. After booster immunization with rgp160, the sera of all vaccinees showed strong antibody responses detected by Western blot and ELISA; 8 had neutralizing activity and 5 had fusion inhibition activity against the homologous strain; 5 blocked binding of CD4 cells to gp120. Cross-reactive neutralization of HIV-1MN was detected in 3 of 8 sera that neutralized HIV-1IIIB. The combination of live recombinant vaccinia followed by subunit booster immunization was more immunogenic than either product alone and represents a promising approach for HIV-1 immunoprophylaxis. Further definition of recombinant vaccinia safety and augmentation of immune responses to geographically prevalent HIV-1 strains will be necessary before expanding clinical trials to high-risk groups.

AIDS Vaccines↗
PubMed1993

Effect of age on cytotoxic T lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine.

Healthy seropositive adults aged < 40 (n = 15), 40-64 (n = 15), and > or = 65 (n = 17) years were parenterally immunized with trivalent subvirion influenza virus vaccine, and their cellular and humoral immune responses were compared. Vaccination resulted in a significant enhancement of class I human leukocyte antigen-restricted influenza A cross-reactive cytotoxic T lymphocyte (CTL) memory. Elderly subjects had significantly lower baseline and peak postvaccination mean percentages of specific lysis of influenza A virus-infected autologous targets but nonetheless mounted CTL responses to vaccine that were comparable in magnitude to those of younger adults. Serologic responses and nasal IgG responses to each of 3 vaccine strains were reduced in magnitude and frequency with advancing age. Parenteral immunization was ineffective at inducing nasal wash IgA antibodies. Between 2 and 12 weeks after vaccination, serum and nasal antibody titers decreased modestly, although the rate of decline was comparable between age groups. The ability of elderly adults to mount CTL responses after influenza vaccination suggests that T cell effector mechanisms may be an important determinant of vaccine-induced protection against serious illness in this age group.

Adult↗
PubMed1993

Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines.

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

Bacterial Outer Membrane Proteins↗
PubMed1993

Immunogenicity of purified F glycoprotein of respiratory syncytial virus: clinical and immune responses to subsequent natural infection in children.

Purified F glycoprotein from respiratory syncytial virus (RSV, subgroup A antigenic type) was evaluated in 18- to 36-month-old children as a vaccine. Children had been previously infected with RSV during natural outbreaks of the virus. Single injections of 5, 20, or 50 micrograms of protein resulted in greater than eightfold increases in ELISA and neutralizing antibodies. Second doses of vaccine did not result in further boosts in antibody. Neutralizing antibodies increased not only to the A2 and Long strains (subgroup A strains) but also to strain 18537 (subgroup B). Four of 11 vaccinees became naturally infected during the subsequent RSV outbreak, suggesting that the vaccine was not effective in preventing recurrent RSV infections. Severe illnesses did not occur, indicating that there was not an increase of severity of infection following vaccine in seropositive children. Only 1 of 8 vaccinees tested had fourfold increases in nasal wash IgA to RSV after immunization. Vaccine strategies to stimulate secretory antibodies as well as circulating neutralizing antibodies to RSV need to be developed.

Animals↗
PubMed1993

Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group Network.

Recombinant gp160 derived from human immunodeficiency virus type 1 (HIV-1)IIIB and produced in mammalian tissue culture cells using a vaccinia virus expression system (rgp160-mam) was evaluated as a vaccine in combination with alum and deoxycholate adjuvant. Sixty low-risk, uninfected subjects received 12.5 micrograms, 50.0 micrograms, or adjuvant control at 0, 1, 6, and 12 months in a randomized, double-blind dose-escalation study. A single injection of 200 micrograms of vaccine was given at 18 months in an open study to 9 vaccines who had received 50 micrograms. The vaccine was safe. Six of 16 subjects receiving 50 micrograms developed neutralizing antibody to HIV-1IIIB. Seven of the 9 boosted with 200 micrograms of vaccine at 18 months developed neutralizing antibodies. Lymphocyte proliferation to rgp160-mam and baculovirus-derived rgp160 and rgp120 was induced in both groups (12.5 and 50.0 micrograms) and appeared after the first dose. Further studies with higher doses of rgp160-mam and vaccines derived from other strains of HIV-1 are warranted.

AIDS Vaccines↗
PubMed1992

Cold-passaged human parainfluenza type 3 viruses contain ts and non-ts mutations leading to attenuation in rhesus monkeys.

Cold-passaged (CP) mutants derived from the JS strain of wild type wt parainfluenza type 3 virus (PIV3) are being evaluated as candidate live virus vaccines. The wt virus was serially passaged 45 times at low temperature and mutant clones with the cold-adapted (CA), temperature-sensitive (ts), and attenuation (ATT) phenotypes were selected following passage levels 12, 18 and 45 (cp12, cp18, and cp45). The cp45 virus was more ts than the cp12 or cp18 mutants, although all 3 mutant viruses were clearly attenuated in rhesus monkeys compared to wild type virus. The mean peak titers of the cp12 and cp18 viruses administered by the intratracheal route were at least 6000-fold lower than JSwt in both the upper and lower respiratory tracts. The cp45 virus was not recovered from monkeys administered virus by the i.t. route alone; however, when the cp45 virus was administered by the intranasal route, it replicated in the upper respiratory tract to a level comparable to that of the cp12 and cp18 viruses, but continued to be markedly restricted in the lower respiratory tract. These data indicate that the cp12 and cp18 viruses contain predominantly non-ts attenuating mutations whereas the cp45 mutant has both non-ts and ts attenuating mutations. Each of the CP mutants induced a high level of resistance to wild type virus challenge. Also, the ATT phenotype of the cp12 and cp18 viruses as measured in rhesus monkeys was stable after replication in chimpanzees or humans, respectively, although the ts phenotype was not. Based on its greater level of temperature sensitivity in vitro and its greater degree of attenuation in rhesus monkeys, the cp45 virus appears to be the most promising vaccine candidate for humans.

Animals↗
PubMed1992

Lymphocyte proliferative responses following immunization with human immunodeficiency virus recombinant GP160. The NIAID AIDS Vaccine Clinical Trials Network.

Following immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, control proteins, and phytohaemagglutinin. Four persons received injections of 40 micrograms or 80 micrograms of rgp160 vaccine at times 0, and 1, 6 and 18 months; one additional volunteer received only three injections of vaccine. Vaccination with rgp160 induced lymphocyte proliferative responses to rgp160, but not to V3 loop peptide. Repeated injection of rgp160 even at low doses induced a cellular immune response which was not attributable to T-cell recognition of the V3 loop peptide.

Adolescent↗
PubMed1992

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Age Factors↗
PubMed1992

Immunization of infants and young children with live attenuated trivalent cold-recombinant influenza A H1N1, H3N2, and B vaccine.

Seventeen triply seronegative infants and young children, and 15 infants and young children seropositive to all three influenza virus strains were vaccinated intranasally with 10(5) TCID50 of each of three (H1N1, H3N2, and B) live attenuated, cold-adapted influenza vaccine strains. Seventeen controls were given placebo. Vaccination with trivalent influenza vaccine was not associated with adverse reactions in triply seronegative or seropositive children. Overall, 12 (71%), 13 (76%), and 13 (76%) of seronegative children were infected by H1N1, H3N2, or B vaccine viruses, respectively, as indicated by viral shedding or by hemagglutination inhibition assay or ELISA antibody response. Of the triply seronegative children, 47% shed all three viruses; 7 children had an antibody rise to all three vaccine viruses and 4 shed all three viruses. A dose of 10(4.4) - 10(5.0) TCID50 of each of three intranasally administered vaccine viruses was safe, immunogenic and antigenic; however, strategies to increase the proportion of children infected by each of the vaccine viruses should be studied, including higher doses and multiple doses of live trivalent vaccine.

Administration, Intranasal↗