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Biomedical subjects

R B Belshe

Publications and source records attributed to R B Belshe.

At least 127 records · Page 7Linked to original sources
PubMed1984

Evaluation of cold-adapted and temperature-sensitive mutants of parainfluenza virus type 3 in weanling hamsters.

Cold-adapted (ca) and temperature-sensitive (ts) mutants of parainfluenza virus 3 were produced by serially passaging wild type (wt) parainfluenza virus 3 at 20 degrees C 45 times. Previously, plaque-purified viruses (clones) were selected from the wt parent and from cold passage levels 7, 12, 18, and 45 and characterized in vitro. In the present study, we evaluated at least one mutant from each cold passage level for attenuation in hamsters. Four of the five mutants tested were ts and ca (one each from cold passage levels 7, 12, 18, and 45) and one was ca but not ts (from cold passage 18). Groups of hamsters were inoculated intranasally with either parent wt or mutant virus. Four or five hamsters from each group were sacrificed prior to inoculation and daily on the first, second, third, fourth, and sixth or seventh day postinoculation and the amount of virus in nasal turbinates and lungs was quantitated. The quantity of virus recovered from the hamsters and the parainfluenza virus 3 antibody titers were inversely related to the cold passage level. Two of the mutants did not replicate in hamsters. Cold adaptation of parainfluenza virus 3 resulted in progressive attenuation of the virus in weanling hamsters. These highly attenuated mutants are suitable for evaluation in children as live virus vaccines.

Animals↗
PubMed1984

Cold-recombinant influenza A/California/10/78 (H1N1) virus vaccine (CR-37) in seronegative children: infectivity and efficacy against investigational challenge.

Forty-seven seronegative children were inoculated intranasally with influenza A/California/10/78 (H1N1) cold-recombinant vaccine (CR-37). Doses ranged from 10(3.2) to 10(7.2) TCID50 per child. The dose necessary to infect 50% of children (one HID50 ) was approximately 10(3.5) TCID50. Only two of eight children given 10(3.2) TCID50 became infected, and neither shed virus. The majority of children who were given 10(4.2), 10(5.2), 10(6.2), or 10(7.2) TCID50 of CR-37 became infected. Twenty-four of 39 children given greater than one HID50 of CR-37 shed vaccine virus. Overall, 31 of 39 became infected, as indicated by shedding of virus or antibody response or both. Although virus was shed for up to 12 days postinoculation, shedding of revertant virus was not detected. Six months after primary vaccination 26 children were challenged intranasally with 10(6.2) TCID50 of CR-37. Of 21 children previously infected with CR-37, only eight had further antibody increase, and none shed vaccine virus. In contrast, five of five (P less than .05) children not infected with CR-37 at the time of initial inoculation were infected with the challenge inoculum (as indicated by a fourfold rise in antibody titer) and three of five children shed vaccine virus. Previous infection with CR-37 conferred significant protection from challenge with a high dose of CR-37.

Antibodies, Viral↗
PubMed1984

Live attenuated influenza A virus vaccines in children: results of a field trial.

One hundred three young children were inoculated intranasally with either influenza A/California/10/78 cold-recombinant vaccine (10(6.7) 50% tissue culture infective doses [TCID50] per child), CR-37 (H1N1), or influenza A/Washington/897/80 cold-recombinant vaccine (10(6.5) TCID50 per child), CR-48 (H3N2). The vaccine was well tolerated. Of the 51 children vaccinated with CR-37 (H1N1), 45 were initially seronegative for this virus; 33 of the 45 became infected with the vaccine virus, as indicated by a fourfold rise in antibody titer or by shedding of vaccine virus. Of the 52 children vaccinated with CR-48 (H3N2), six were initially seronegative and all were infected; 46 were initially seropositive and 25 of these children developed fourfold rises in antibody titer. An outbreak of influenza A (H3N2 type predominated) occurred in Huntington one to three months after the children were vaccinated. Significantly fewer febrile illnesses occurred in the CR-48 (H3N2) vaccine group than among the CR-37 (H1N1) vaccine group. Hemagglutination inhibition antibody (titer, greater than or equal to 1:32) to H3N2 was significantly associated with protection from illness and infection with influenza A/H3N2.

Antibody Formation↗
PubMed1983

Impact of viral respiratory diseases on infants and young children in a rural and urban area of southern West Virginia.

Acute viral respiratory disease occurring in children residing in the community of Huntington, West Virginia (urban children) or in the hollows surrounding Huntington (rural children) was evaluated from September 1978 through March 1980. Cohorts of ambulatory children residing in each area were studied for the occurrence of mild to moderate respiratory disease. All children admitted to hospitals were evaluated for the occurrence of severe viral respiratory disease. Respiratory secretions were obtained from children for isolation of viruses. Epidemics of illnesses occurred simultaneously in the urban and rural groups of children. Among both the urban and rural ambulatory children, adenoviruses were the most common viruses isolated, and respiratory syncytial virus was the second most common viral pathogen isolated. Among the urban and rural hospitalized children, respiratory syncytial virus was the most common virus isolated. The distribution of the diagnoses, pneumonia, bronchiolitis, or croup, was similar among the urban and rural children who required hospitalization. The risk of hospitalization because of respiratory disease was found to be one in every 20 children during the first four years of life, and the estimated risk of hospitalization because of respiratory syncytial virus infection was one in 30. No differences were detected in the incidence of severe viral respiratory disease among children residing in urban or rural areas in southern West Virginia.

Child, Preschool↗
PubMed1982

Cold adaptation of parainfluenza virus type 3: induction of three phenotypic markers.

In order to attenuate parainfluenza type 3 virus, a wild type strain that was isolated from a child with respiratory disease was adapted to replicate in African green monkey kidney cells at 20 degrees C. Replication at 20 degrees C was not a property of the wild type virus. The virus was serially passaged 45 times in the cold, and clones were selected following passage levels 7, 12, 18, and 45. The population of cold-adapted virus was found to be progressively enriched with temperature sensitive (ts) mutants. After 7 passages in the cold, 1 of 9, and after 12 passages in the cold, 3 of 12 clones were temperature sensitive. Following 18 passages in the cold, 80% of the clones were temperature sensitive and after 45 passages in the cold, all clones were temperature sensitive. In addition to being temperature sensitive each ts clone manifested the tiny plaque morphology. Each temperature-sensitive clone was also cold adapted. Some clones were cold adapted but were not temperature sensitive. The mutants were found to be genetically stable when serially passaged at 32 degrees, 35 degrees, or 39 degrees C. The mutants may possess the necessary degree of attenuation for use as live attenuated intranasal vaccines.

Adaptation, Physiological↗
PubMed1982

Parenteral administration of live respiratory syncytial virus vaccine: results of a field trial.

A live respiratory syncytial virus (RSV) vaccine administered parenterally was evaluated for efficacy in a double-blind, placebo-controlled field trial in 510 children six to 47 months of age. Among the 233 recipients of live RSV vaccine, 68 of 98 initially seronegative children (as determined by enzyme-linked immunosorbent assay) developed antibody to RSV; 25 of the 30 initially seronegative children who did not develop antibody were less than 12 months old, which suggested that very low levels of maternal antibody (undetectable by enzyme-linked immunosorbent assay) inhibited replication of the vaccine virus. The children were monitored for the occurrence of naturally acquired RSV infection in two RSV epidemics, and there was no difference in the frequency of upper or lower respiratory tract disease caused by RSV between the live RSV vaccine recipients who developed vaccine-induced antibody and the placebo vaccine recipients. Thus, this live RSV vaccine administered parenterally was not efficacious.

Antibodies, Viral↗
PubMed1982

Comparison of enzyme-linked immunosorbent assay and neutralization techniques for measurement of antibody to respiratory syncytial virus: implications for parenteral immunization with live virus vaccine.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) to detect low levels of antibody to respiratory syncytial (RS) virus was compared with a tube dilution neutralization test (NEUT) on sera obtained from children who received a parenteral live RS virus vaccine. Among the children who developed antibody in response to live RS virus vaccine. ELISA was as sensitive as NEUT at detecting antibody increases. Some children who did not have detectable prevaccine ELISA antibody possessed NEUT antibody; these children were generally less than 12 months old, suggesting that they had low levels of maternal antibody. Low levels of NEUT or ELISA antibody were associated with the absence of antibody increases after injection of live RS virus vaccine. The quantity of antibody stimulated by this live RS virus vaccine was small compared with that which was stimulated by naturally acquired RS virus infection. We concluded that ELISA is a satisfactory test for determining antibody to RS virus in vaccine field trials, given the understanding that low levels of preexisting antibody are not detected in some instances.

Antibodies, Viral↗
PubMed1982

Administration of a highly attenuated, live respiratory syncytial virus vaccine to adults and children.

A highly attenuated respiratory syncytial virus (RSV) experimental vaccine, RSV ts-2, was sequentially evaluated in adults, seropositive children, and finally, fully susceptible seronegative children. The vaccine was administered intranasally in doses ranging from 10(5.2) to 10(6.3) PFU/ml. In both adults and children, the vaccine proved to be poorly infectious. Although poor infectivity would not have been predicted from tissue culture studies of RSV ts-2 growth, the human experience closely parallels the experience in a series of animal models, including the chimpanzee. The poor infectivity of this RSV vaccine virus preparation suggests that the postulated defect in the RSV ts-2 fusion protein may be important in determining in vivo infectivity of RSV.

Adult↗
PubMed1982

Serological diagnosis of influenza B virus infection: comparison of an enzyme-linked immunosorbent assay and the hemagglutination inhibition test.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to influenza B virus was compared with that of the hemagglutination inhibition test on acute- and convalescence-phase sera obtained from adults and children infected with influenza B virus. Two whole virus, tissue culture-grown antigen preparations were used in the ELISA, influenza B/West Virginia/81 and influenza B/Hong Kong/72. Four antigens were used in the hemagglutination inhibition test. These included the tissue culture-grown whole virus antigens that were used in the ELISA. In addition the standard egg-grown antigens, influenza B/Singapore/79 and influenza B/Hong Kong/72, were included for comparison. The ELISA antibody titer was significantly correlated to the hemagglutination inhibition antibody titer, and 10 of 10 adults and 17 of 21 children infected with influenza B had fourfold antibody increases as detected by ELISA with either antigenic type of tissue culture-grown whole virus. Increases in geometric mean antibody titers of 16- to 71-fold were detected by ELISA. Increases in geometric mean antibody titers of 3- to 10-fold were detected by hemagglutination inhibition depending on the type of antigen utilized. We found that ELISA with whole virus antigens was a sensitive and specific test for the detection of antibody to influenza B virus.

Adult↗
PubMed1982

Nosocomial influenza B virus infection in the elderly.

A hospital-acquired outbreak of influenza-like illness that involved 29 patients during 4 weeks was detected in March 1980. The average age of the patients was 63 years. Eighteen of the 29 patients with symptoms had influenza B virus infection documented by virus isolations, fourfold or greater hemagglutination inhibition antibody increases, or both. The attack rate among all hospitalized inpatients was 20%. Absenteeism of the hospital staff because of influenza-like illnesses preceded the outbreak by several weeks, suggesting staff-to-patient transmission. The patients' sera during acute illness had low hemagglutination inhibition antibody titers (geometric mean titer of 1:21) against contemporary influenza B virus antigens, indicating that the patients were highly susceptible to influenza B virus. Only one patient had received trivalent influenza vaccine during the preceding year. The excess hospital cost resulting from the outbreak was +13 270 or +458 per patient. Our observations show that the elderly are at risk of developing nosocomial influenza B virus infection and that these illnesses are costly. Continued efforts to develop efficient influenza immunization programs for elderly persons and hospital staff are worthwhile.

Aged↗
PubMed1978

Experimental respiratory syncytial virus pneumonia in cebus monkeys.

Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.

Animals↗