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Biomedical subjects

W Paul Glezen

Publications and source records attributed to W Paul Glezen.

28 records · Page 2Linked to original sources

Effect of maternal antibodies on the infant immune response.

Transplacentally-acquired antibodies are important for protection of infants in the early months of life. Maternal antibodies may dampen the infant's primary antibody response to infection or immunization. Even without a measurable response to the initial antigen exposure, the infant will usually have evidence of priming at the time of repeat exposure. No evidence for the development of fetal tolerance after immunization during pregnancy has occurred subsequently in infants following active vaccination.

Adult↗

Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women.

A randomized, double-blind, placebo controlled study was carried out to determine the safety and immunogenicity of RSV PFP-2 vaccine (Wyeth-Lederle Vaccines, NY) in 35 healthy women in the third trimester of pregnancy and their offspring. Infants were followed during their first RSV season for occurrence and severity of respiratory illnesses. RSV-PFP-2 vaccine was safe and well tolerated by pregnant women. Mild pain at the site of injection occurred in 65% of PFP-2 and 13% of placebo recipients (P=0.005). There were no systemic reactions, fever, or serious adverse events associated with vaccine administration in mothers. All 35 infants were born healthy, and there were no differences among the groups in perinatal or neonatal outcomes, growth and development in the first year of life. During the RSV season, there was no increase in the frequency or morbidity associated with respiratory tract illnesses in infants of vaccine recipients. 15/20 (75%) vaccine recipients had a response to PFP-2 by Western blot vs. 0/15 placebo recipients (P<0.01). 19/20 (95%) vaccine recipients had a > or =4 fold rise in IgG ELISA Ab after immunization with PFP-2 vs. 0/15 placebo recipients (P<0.01). Geometric mean concentrations of IgG ELISA Ab were 4 fold higher in infants of vaccine recipients at birth, 2 and 6 months after delivery than in infants of placebo recipients (P<0.01). A modest (0.5log2) increase in neutralization Ab was observed in vaccine recipients and their infants. The half-life of maternal antibodies in infants was > or =3 weeks. There was no evidence of enhanced T-cell or cytokine activity in infants of vaccine recipients vs. infants of placebo recipients. Vaccine specific anti-F IgA and IgG concentrations in breast milk were higher in mothers who received RSV-PFP-2.

Adult↗

Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies.

OBJECTIVE: To determine if respiratory syncytial virus (RSV) specific, serum antibody titers correlate with protection against RSV associated-hospitalization at all ages. DESIGN: Participants who were enrolled in a trial to determine the frequency of specific virus infections associated with hospitalization [J. Am. Med. Assoc. 283 (2000) 499] were included in our analysis if they were enrolled from July 1991 to June 1993, had a culture for virus isolation, and provided blood samples at hospitalization and 14-60 days later. RSV infection was defined by a positive culture and/or serology. Microneutralization, ELISA to the fusion (F) protein and Western blot were the serological assays that were used to determine correlates of immunity. RESULTS: One hundred and seventy-five individuals, 1 month to 89 years old, out of 538 patients hospitalized with an acute respiratory infection met the criteria for analysis. RSV associated-hospitalization occurred in 11 (40.7%) of 27 infants (<1 year), 8 (38.1%) of 21 young children (1 to <5 years), and 15 (11.8%) of 127 children and adults (> or =5 years). At the time of hospitalization, geometric mean neutralizing antibody titers (log(2)) to RSV/A and RSV/B, and geometric mean binding antibody titer (log(2)) to F protein were significantly higher in patients with non-RSV associated-hospitalization compared to those with RSV associated-hospitalization (RSV/A: 7.9 versus 6.1, P<0.001; RSV/B: 9.4 versus 7.3, P<0.001; ELISA-F, 13.9 versus 12.6, P=0.01). For every 1 log(2) increase in titer of neutralizing antibodies to RSV/A and RSV/B, and binding antibody to F protein there was a significant increase in the likelihood of not having an RSV associated-hospitalization by 22.3, 25, and 24.4% respectively. A minimal protective threshold titer of > or =6.0 (odds ratio 3.5; 95% CI 1.4-9.1) and > or =8.0 log(2) (odds ratio 2.9; 95% CI 1.1-7.7) against RSV associated-hospitalization was established for neutralizing antibodies to RSV/A and RSV/B; a threshold titer could not be established for binding antibody to F protein. CONCLUSION: Participants with naturally acquired serum neutralizing antibody levels at least equal to the minimal protective threshold titer were approximately three times more likely not to have an RSV associated-hospitalization. We speculate that achieving a minimal protective threshold antibody titer through active immunization will significantly reduce RSV associated-hospitalization among all ages.

Adolescent↗

Immunogenic protein contaminants in pneumococcal vaccines.

Currently available pneumococcal vaccines were examined for contamination by pneumococcal surface protein A (PspA) and pneumococcal surface adhesin A (PsaA). PspA could be detected in some (but not all) lots of 23-valent polysaccharide vaccine. Many lots of pneumococcal vaccines, including the heptavalent conjugate vaccine, were found to elicit small (but variable) antibody responses to PspA, PsaA, or both. The degree of contamination was highly variable, and this should be considered in pneumococcal vaccine evaluations or when capsular polysaccharide is used for pneumococcal antibody assays.

Adhesins, Bacterial↗

Molecular epidemiology of influenza A(H3N2) virus reinfections.

Between 1979 and 1989, families enrolled in the Houston Family Study were prospectively monitored for influenza virus infections. Reinfection with the H3N2 subtype occurred in a number of family members, and 6 pairs of isolates (interval between collection of first and second isolate, 2-5 years) were available for molecular analysis. Changes in the hemagglutinin genes of pairs of viruses isolated from the same individuals were examined to determine the molecular basis for reinfection. The findings of this study indicate that reinfection of an individual by viruses of the same subtype may occur within a relatively short period of time when the paired strains have genetically distinct hemagglutinin genes in which amino acid changes are present in the defined antigenic sites.

Adolescent↗

Influenza vaccination for healthy children.

Influenza virus infections cause vaccine-preventable but uncontrolled epidemic disease in the United States. Population dynamics dictate that the burden of disease will increase dramatically over the next 20 years if new strategies are not implemented. New weapons for the diagnosis, treatment and prevention of influenza are now available and should be implemented immediately. The impact of disease in children has been largely overlooked. Control measures should be focused on the prevention of disease in children, who have the highest annual attack rates. The new live attenuated nasal spray influenza vaccine is particularly effective in healthy children who would benefit most from universal immunization.

Acetamides↗