Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

University of Virginia

Status and phase: Completed; Phase 2; Phase 1

Conditions: Healthy Volunteers

Treatments: Biological: human rhinovirus; Other: no intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT02796001

16-0055

Details and patient eligibility

About

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.

Full 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. .

Enrollment: 46 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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46 participants in 3 patient groups

RV16 infected volunteers re-challenged with RV16

Active Comparator group

Description:

volunteers re-challenged with RV16

Treatment:

Biological: human rhinovirus

RV infected volunteers re-challenged with RV39

Active Comparator group

Description:

volunteers re-challenged with RV39

Treatment:

Biological: human rhinovirus

RV infected not rechallenged

Other group

Description:

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

Treatment:

Other: no intervention