Healthy Volunteers
Conditions
Brief summary
The primary objective of this study is to assess the relationship between rhinovirus specific T-cell immunity and the human host response to primary rhinovirus challenge and subsequent secondary challenge with either homologous or heterologous rhinovirus serotypes.
Detailed description
The primary objective of this study is to assess the relationship between RV-specific T-cell immunity and the human host response to primary RV challenge and subsequent secondary challenge with either homologous or heterologous RV serotypes. The overall hypothesis that will be addressed by the mechanistic studies in this proposal is that T helper (Th) and T follicular helper (Tfh) cells directed against conserved RV epitopes expand upon RV exposure and some of these cells persist as stable cross-reactive memory populations capable of displaying lineage-specific protective functions upon re-infection with related or unrelated strains of RV. The human specimens collected in this study will be analyzed with a variety of state-of-the-art techniques to provide an in depth description of T-cell responses to RV infection, and the correlation of these responses with viral infection, antibody responses, and illness. Beyond this objective, by using a systems biology approach, we aim to gain new insight into the role of diverse cell types involved in adaptive immunity to RV. .
Interventions
BIOLOGICALhuman rhinovirus
human rhinovirus
OTHERno intervention
4 volunteers were not re-challenged and did not participate in the second challenge
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Volunteers who were infected with RV16 by experimental challenge were eligible for participation by re-challenge with either RV16 or RV39 to assess the host response to homologous or heterologous rechallenge.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subject must be 18-40 years of age 2. Subject must read and sign a copy of the approved Consent Form 3. Subject must have a serum neutralizing antibody titer of ≤1:2 to rhinovirus type 39 and rhinovirus type 16 4. Female subjects must be using an effective birth control method. 5. Total IgE \<150 IU/ml.
Exclusion criteria
1. Any clinically significant abnormalities of the upper respiratory tract 2. Any clinically significant acute or chronic respiratory illness 3. Any clinically significant bleeding tendency by history 4. Hypertension that requires treatment with antihypertensive medications 5. History of angina or other clinically significant cardiac disease 6. Any upper respiratory infection or allergic rhinitis in the two weeks prior to the start of the study 7. Any medical condition that in the opinion of the Investigator is cause for exclusion from the study 8. Use of any anti-inflammatory (steroids or NSAIDs) or cough/cold preparation in the 1 month prior to the study 9. Regular use of tobacco in the last 6 months (ie. more than 2 days out of 7) or inability to refrain from smoking during the study 10. Inability to refrain from the use of common cold therapies in the 5 days after each rhinovirus challenge. 11. Participation in any other clinical drug trial in the month prior to the study 12. Female subjects with a positive urine pregnancy screen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virus Infection | Volunteers were cultured daily for detection of virus shedding for 5 days after the virus re-challenge and serum was collected for viral serology 4 weeks after virus re-challenge | Number infected after re-challenge with RV16 compared to RV39 as determined by virus isolation in cell culture or viral serology |
Countries
United States
Participant flow
Recruitment details
Volunteers who participated in the study were individuals who had previously been challenged and infected with RV16 in the human rhinovirus experimental challenge model and agreed to be re-challenged with either RV16 or RV39
Pre-assignment details
Volunteers were initially challenged with RV16 to provide a uniform baseline for the subsequent randomization and re-challenge with either a homologous serotype (RV16) or a heterologous serotype (RV39). 46 subjects met the baseline criteria but 3 declined further participation and 1 was ill on the day of re-challenge and was removed from the study by the investigator. 42 subjects were randomized and re-challenged with rhinovirus.
Participants by arm
| Arm | Count |
|---|---|
| RV16 Infected Volunteers Re-challenged With RV16 volunteers re-challenged with RV16
human rhinovirus: human rhinovirus | 20 |
| RV16 Infected Volunteers Re-challenged With RV39 volunteers re-challenged with RV39
human rhinovirus: human rhinovirus | 22 |
| no Intervention 4 volunteers were infected with RV16 and were eligible for re-challenge. Three volunteers declined re-challenge and one was removed from the study prior to re-challenge | 4 |
| Total | 46 |
Baseline characteristics
| Characteristic | RV16 Infected Volunteers Re-challenged With RV16 | RV16 Infected Volunteers Re-challenged With RV39 | no Intervention | Total |
|---|---|---|---|---|
| Age, Continuous | 20.7 years STANDARD_DEVIATION 2.43 | 19.8 years STANDARD_DEVIATION 1.87 | 19.25 years STANDARD_DEVIATION 0.5 | 20.1 years STANDARD_DEVIATION 1.91 |
| previously infected with RV16 | 20 Participants | 22 Participants | 4 Participants | 46 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 19 Participants | 3 Participants | 37 Participants |
| Region of Enrollment United States | 20 participants | 22 participants | 4 participants | 46 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 2 Participants | 24 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 2 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 2 / 46 | 1 / 20 | 1 / 22 |
| serious Total, serious adverse events | 0 / 46 | 0 / 20 | 0 / 22 |
Outcome results
Primary
Virus Infection
Number infected after re-challenge with RV16 compared to RV39 as determined by virus isolation in cell culture or viral serology
Time frame: Volunteers were cultured daily for detection of virus shedding for 5 days after the virus re-challenge and serum was collected for viral serology 4 weeks after virus re-challenge
Population: all volunteers re-challenged
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RV16 Infected Volunteers Re-challenged With RV16 | Virus Infection | 8 Participants |
| RV16 Infected Volunteers Re-challenged With RV39 | Virus Infection | 18 Participants |