Evaluating the Asthmatic Response to an Experimental Infection With Rhinovirus in the Atopic

Using rhinovirus strain 16 (RV-16) for inoculation, this study is designed to examine
mechanisms of the asthmatic response to RV in the atopic host. In keeping with this, the
primary objective of this investigation will be to test the hypothesis that mild asthmatics
enrolled in this study will experience significantly increased lower respiratory tract
symptoms over the first 4 days after experimental inoculation with RV-16 than non-allergic,
non-asthmatic controls (as shown in our previous studies). It is anticipated that the results
will serve to guide the development of new treatments to prevent asthma attacks provoked by
RV. This will be a 5 week longitudinal study of 18 young allergic adults with mild asthma and
18 non-asthmatic controls who will be evaluated for 1 week to establish baseline symptoms and
lung function, followed by an inoculation with rhinovirus (strain-16) and subsequent clinical
and laboratory (mechanistic) monitoring for an additional 4 weeks. To participate in this
study, subjects must live within 90 minutes by car from the University of Virginia.

Note: This study has been reviewed and is being monitored for safety by the NIH/NIAID Safety
Monitoring Committee and by teh University of Virginia IRB (#12673). The virus pool used for
inoculation has been produced under GMP conditions and is approved for this research by the
FDA.

Inclusion Criteria • ALL SUBJECTS:

- Subjects must be able to understand and provide written informed consent

- Age 18 to < 40 years of age, any gender, any racial/ethnic origin.

- Participant must be willing to comply with study procedures and requirements.
Participant must be considered eligible for participation based on results of
screening procedures conducted by protocol number 20100686 at VCU and IRB# 12656 at
UVA.

Subjects with asthma

Criteria for inclusion will include those:

- with physician-diagnosed, mild asthma who are only using bronchodilators (e.g.
albuterol) for symptom control.

- Asthma Control Test (ACT) Questionnaire Score a > 19 at enrollment (See Appendix:
Asthma Control Test).

- Short-acting beta-agonist use < daily in last 4 weeks

- FEV1 > 70%, or FEV1/FVC ratio > 75% for subjects with FVC values between 80 and 87%
predicted whose FEV1 values fall below 70%. a positive methacholine challenge test
(i.e. at least a 20% fall in FEV1) at a methacholine concentration of 16 mg/ml or less
(15). The methacholine test will not be done if subjects have used albuterol within 4
hours of the test procedure.Evidence for atopy demonstrated during screening (under
IRB protocol# 12656) as judged by positive prick skin tests to one or more
aero-allergens.

Control subjects. Criteria for inclusion will include those who do not have a history of
asthma or allergic disorders (e.g. allergic rhinitis, atopic dermatitis, or food
allergies).

Exclusion Criteria ALL SUBJECTS:

- Inability or unwillingness of a participant or subject's legal representative to give
written informed consent and HIPPA authorization

- Positive test for serum neutralizing antibody to RV-16. Subjects with a neutralizing
antibody titer > 1:4 will be excluded.

- Chronic heart disease, lung diseases other than asthma, or other chronic illnesses,
including primary and/or secondary immunodeficiency.

- An upper or lower respiratory tract infection within six weeks prior to enrollment

- Who have required nasal or sinus surgery, excluding surgery for a deviated septum
within 12 months prior to enrollment.

- Who have a 5 pack/year history of smoking, or any smoking within the last 6 months.

- Female subjects who are or who plan to become pregnant during the study, or who are
nursing a baby. Additionally, to be included in this study, a woman of child-bearing
potential must have a negative urine pregnancy test at screening, during the run-in,
and prior to viral inoculation and agree to use an effective method of birth control
such as, but not limited to, birth control pills, contraceptive foam, diaphragm, IUD,
abstinence, or condoms.

- Absolute neutrophil count (ANC) < 1800 cells/mm3 (or 1.8 K/uL) detected during
screening within 6 weeks of enrollment.

Subjects with asthma

Criteria for exclusion will include those:

- Who have required inhaled steroids (used for asthma), nasal steroids (used for
allergic rhinitis), cromolyn, nedocromil sodium, ipratropium bromide, or leukotriene
modifiers during the month prior to enrollment, oral steroids within 6 weeks of
enrollment, omalizumab (Xolair®) within 12 months prior to enrollment, or who are
currently using beta adrenergic blocking agents.

- Who have been hospitalized or treated in the emergency room (unless the treatment
involved the use of a bronchodilator only) for asthma within the last three years.

- To avoid RV-16 inoculations in subjects with more restrictive lung volumes, those
whose FVC is < 80% predicted will be excluded. Subjects who are currently receiving
allergen immunotherapy (IT), or who have received allergen IT within the last 3 years.

- Subjects who have had one or more night time awakenings caused by asthma symptoms
and/or who have needed their SABA (albuterol) inhaler for asthma symptoms > 4 days
during the week before enrollment, or during the week before the inoculation with
RV-16.

Control subjects

• Who have a positive methacholine test, or positive prick skin tests at screening under
IRB protocol # 12656.