Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

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. .

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.