Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Biological: human rhinovirus; Other: no intervention

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. .

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RV16 infected volunteers re-challenged with RV16; volunteers re-challenged with RV16	Biological: human rhinovirus; human rhinovirus
Active Comparator: RV infected volunteers re-challenged with RV39; volunteers re-challenged with RV39	Biological: human rhinovirus; human rhinovirus
Other: RV infected not rechallenged; 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	Other: no intervention; 4 volunteers were not re-challenged and did not participate in the second challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virus Infection	Number infected after re-challenge with RV16 compared to RV39 as determined by virus isolation in cell culture or viral serology	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

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Ronald Turner, MD, Univ of Virginia

Publications and helpful links

General Publications

• Barone SM, Paul AG, Muehling LM, Lannigan JA, Kwok WW, Turner RB, Woodfolk JA, Irish JM. Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy. Elife. 2021 Aug 5;10:e64653. doi: 10.7554/eLife.64653.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2017
• Primary Completion (Actual): May 1, 2020
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (Estimate): June 10, 2016

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 2, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: 16-0055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No