Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Other: no intervention; Biological: human rhinovirus

• Registration Number: NCT02796001
• Lead Sponsor: University of Virginia

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. .

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-06-07
• Study First Submitted QC: 2016-06-07
• Study First Posted: 2016-06-10
• Study Start: 2017-09-25
• Primary Completion: 2020-05-01
• Study Completion: 2020-05-01
• Results First Submitted: 2022-02-09
• Status Verified: 2022-06
• Results First Submitted QC: 2022-06-02
• Last Update Submitted: 2022-06-02
• Results First Posted: 2022-06-06
• Last Update Posted: 2022-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RV infected not rechallenged	no intervention	Volunteers who were infected with RV16 and eligible for re-challenge but who were not re-challenged due to voluntary withdrawal (3) or removal for exclusion criteria
RV16 infected volunteers re-challenged with RV16	human rhinovirus	volunteers re-challenged with RV16
RV infected volunteers re-challenged with RV39	human rhinovirus	volunteers re-challenged with RV39

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States