Biomedical subjects

John J Treanor

Publications and source records attributed to John J Treanor.

7 recordsLinked to original sources

PubMed2004

Dose-dependent neutralizing-antibody responses to vaccinia.

To evaluate the humoral immune responses to smallpox-vaccine stocks currently available in the United States (Dryvax; Wyeth) and to generate data for comparison of responses to newly produced lots of smallpox vaccine, we evaluated dose-response effects, using undiluted and diluted smallpox vaccine. At 28 and 56 days after vaccination, serum samples were obtained from vaccinated subjects (N=674) who had participated in a randomized, single-blinded trial of an undiluted or a 1 : 5 or 1 : 10 dilution of smallpox vaccine and who subsequently were tested for plaque-reduction neutralizing-antibody titer. All subjects who developed a vesicle after vaccination also developed neutralizing antibodies by day 28. Subjects given either a 1 : 5 or 1 : 10 dilution of vaccinia had significantly higher neutralizing-antibody titers than did subjects given undiluted vaccine. Larger lesion size and fever after vaccination were associated with significantly higher neutralizing-antibody titers after vaccination.

Adolescent↗

PubMed2004

Experimental infection of humans with A2 respiratory syncytial virus.

Development of a readily available challenge model of human respiratory syncytial virus (RSV) infection would be a useful tool for evaluation of antiviral agents and vaccine candidates. Accordingly, we evaluated a new challenge pool of RSV A2 virus, provided by the National Institutes of Allergy and Infectious Diseases. Healthy adults subjects were inoculated intranasally with various dilutions of the pool, and virus shedding, clinical symptoms, and immune response were studied. In a preliminary study of 36 randomly selected volunteers, stratified by serum neutralization titer both higher inoculum dose (4.7 log(10) TCID(50) virus) and lower antibody titer (<==10.36 log(2)), were associated with infection. In a second confirmatory study 12 of 13 (92%) subjects selected for low serum neutralizing activity shed virus after challenge with the high inoculum of virus. Mean peak virus shedding was 2.2 log(10) TCID(50)/mL nasal wash with a mean duration of 4 days. None of the subjects developed signs or symptoms of lower airway disease, although respiratory symptom scores and nasal mucus weight were temporally correlated with virus shedding. Prescreening for low levels of neutralizing antibody may allow selection of subjects with relatively higher susceptibility to experimental infections. This model provides a safe and efficient mechanism for proof-of-concept studies of anti-viral agents and RSV vaccines, as well as for investigation of immune responses to infection.

Administration, Intranasal↗

PubMed2004

Introduction.

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Age Distribution↗

PubMed2003

Comparison of quantitative reverse transcription-PCR to viral culture for assessment of respiratory syncytial virus shedding.

Respiratory syncytial virus (RSV) has recently been recognized as a serious pathogen in elderly and immunocompromised adults. Diagnosis of acute infection in adults is often difficult due to the insensitivity of viral culture, and reverse transcription-PCR (RT-PCR) is a more sensitive alternative. The relationship of quantitative RT-PCR to viable virus has never been studied for RSV. Therefore, we compared a quantitative real-time RT-PCR with viral culture to assess viral load in adult volunteers challenged with the RSV A2 strain. Twelve of 13 volunteers were infected, and there was a high correlation (r = 0.84) between quantitative RT-PCR and viral titer by cell culture. However, RT-PCR was more sensitive, with 73 of 169 (43%) samples positive compared to 58 (34%) samples positive by culture. The correlation between the two tests was highest early in the course of viral shedding (r = 0.91, days 0 to 6), whereas during days 7 to 13, there was more variability (r = 0.70). All subjects were culture negative by day 11, whereas one subject remained RT-PCR positive on day 12. All subjects were RT-PCR negative at day 28 postinfection. Quantitative RT-PCR has an excellent correlation with viral titers, as measured by culture, and should be a useful tool for future studies addressing viral load and disease pathogenesis.

Adult↗

PubMed2002

Clinical responses to undiluted and diluted smallpox vaccine.

BACKGROUND: To evaluate the potential to increase the supply of smallpox vaccine (vaccinia virus), we compared the response to vaccination with 10(8.1), 10(7.2), and 10(7.0) plaque-forming units (pfu) of vaccinia virus per milliliter. METHODS: In this randomized, single-blind, prospective study, 680 adults who had not been previously immunized were inoculated intradermally with undiluted vaccine (mean titer, 10(8.1) pfu per milliliter), a 1:5 dilution, or a 1:10 dilution of vaccinia virus with use of a bifurcated needle, and the site was covered with a semipermeable dressing. Subjects were monitored for vesicle formation (an indicator of the success of vaccination) and adverse events for 56 days after immunization. RESULTS: Success rates did not differ significantly among the groups and ranged from 97.1 to 99.1 percent after the first vaccination. Both the undiluted and diluted vaccines were reactogenic. In addition to the formation of pustules, common adverse events included the formation of satellite lesions, regional lymphadenopathy, fever, headache, nausea, muscle aches, fatigue, and chills consistent with the presence of an acute viral illness. Generalized and localized rashes, including two cases of erythema multiforme, were also observed. CONCLUSIONS: When given by a bifurcated needle, vaccinia virus vaccine can be diluted to a titer as low as 10(7.0) pfu per milliliter (approximately 10,000 pfu per dose) and induce local viral replication and vesicle formation in more than 97 percent of persons.

Adolescent↗

PubMed2002

Chronic stress in nonelderly caregivers: psychological, endocrine and immune implications.

OBJECTIVE: This investigation examined whether the immune dysregulation that characterises elderly informal caregivers (e.g., spousal caregivers of dementia patients) extends to a younger caregiver population, specifically spousal carers of patients with multiple sclerosis (MS). METHOD: MS spousal caregivers (n=41, mean age 43 years, 14 women, 27 men) and noncaregiving controls (n=62, mean age 33 years, 44 women, 18 men) were recruited. Psychological morbidity (i.e., self-reported stress, anxiety and depression), endocrine activity (i.e., salivary cortisol and DHEAs) and immunity (i.e., IgG and HAI responses to influenza vaccination and IFN-gamma and IL-4 levels) were assessed. RESULTS AND CONCLUSIONS: MS caregivers and noncaregivers did not differ significantly in their IgG or HAI responses to influenza vaccination or in levels of IFN-gamma and IL-4. However, it remains unclear whether the "preserved" immune response of these younger caregivers was due to (1) an absence of immune senescence, (2) a relative absence of psychological morbidity, or both.

Adult↗

PubMedDate not supplied

Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body?

OBJECTIVES: This study attempted to determine whether stress of moderate intensity could modulate the antibody response to an influenza vaccination in healthy young adults, identify critical periods during which stress could influence antibody response, and delineate behavioral and biological pathways that might explain relations between stress and antibody. METHODS: A cohort of 83 healthy young adults underwent 13 days of ambulatory monitoring before, during, and after vaccination. Four times daily, subjects reported the extent to which they felt stressed and overwhelmed and collected a saliva sample that was later used to measure cortisol. A battery of health practices (cigarette smoking, alcohol use, physical activity, sleep hygiene) was assessed daily. Antibody titers to the vaccine components were measured at baseline and at 1-month and 4-month follow-up assessments. RESULTS AND CONCLUSIONS: To the extent that they reported higher levels of stress across the monitoring period, subjects exhibited poorer antibody responses to the New Caledonia strain of the vaccine. Stress ratings on the 2 days before the vaccine and the day it was given were not associated with antibody response. However, the 10 days afterward appeared to be a window of opportunity during which stress could shape the long-term antibody response to varying degrees. With respect to potential mediating pathways, little evidence emerged in favor of cortisol secretion, alcohol consumption, physical activity, or cigarette smoking. However, analyses were consistent with a pattern in which feelings of stress and loss of sleep become locked into a feed-forward circuit that ultimately diminishes the humoral immune response. These findings may shed light on the mechanisms through which stress increase vulnerability to infectious disease.

Adolescent↗