Immunogenicity of the 9-Valent Human Papillomavirus Recombinant Vaccine in People With Idiopathic CD4 T Cell Lymphocytopenia

As observed in other immunocompromised individuals with selective or combined T cell
deficits, the prevalence and morbidity of human papillomavirus (HPV)-related disease is
increased in patients with idiopathic CD4 T cell lymphocytopenia (ICL). The high burden and
aggressive clinical course of HPV-associated disease in patients with ICL requires the
development of effective preventive measures in this specific population. The protection from
a broader range of HPV types offered by the 9-valent vaccine is expected to be particularly
beneficial in this population. This applies even to patients with a history of type-specific
HPV-associated disease, as this population may remain at a higher risk of acquisition of
infection with new oncogenic HPV types even with increasing age. However, the immunogenicity
of vaccines and in particular HPV preventive vaccines has never been systematically studied
in patients with ICL.

This will be a phase 2, open-label study to assess the immunogenicity of the U.S. Food and
Drug Administration (FDA)-approved 9-valent HPV recombinant vaccine GARDASIL 9 in patients
18- through 60-years-old with ICL, irrespective of HPV serostatus, presence of HPV-associated
diseases, or previous immunization with bivalent or quadrivalent HPV vaccine, as well as
healthy controls matched to the ICL patient group for age and gender. The study will take
place at a single site (National Institutes of Health Clinical Center, Bethesda, MD).
Participants will be assessed at baseline for history and/or clinical evidence of
HPV-associated disease. Those with a history of or current HPV skin or mucosal disease will
undergo clinically indicated evaluation and be referred for clinical care as needed. We will
administer the vaccine according to the standard 3-dose schedule approved by the FDA for
individuals 9 through 45 years of age, with the second and third doses administered at least
2 months and at least 6 months, respectively, after the first dose. Follow-up visits will
occur 1 and 18 months after completion of the vaccination schedule. Blood will be collected
at each study visit for safety and immunogenicity testing.

- INCLUSION CRITERIA:

1. Aged 18 to 60 years.

2. Able to provide informed consent.

3. Female study participants who engage in sexual activities that can result in
pregnancy must agree to use one of the contraceptive methods listed below at
every potentially reproductive sexual encounter, beginning at the baseline visit
and continuing until 3 months after discontinuation of the study agent.
Acceptable methods are as follows:

- Male or female condom with spermicide.

- Hormonal (e.g., consistent use of oral contraceptive pill daily or other hormonal
method such as contraceptive implant or injection). Hormonal methods must be started 1
month prior to receiving the first dose of study agent.

- Diaphragm or cervical cap.

- Intrauterine device (IUD).

4. Must meet criteria for 1 of the 2 study groups, as follows:

- Patients with ICL must have:

- documented ICL, defined as CD4 cell count < 300 cells/microL in at least 2
different measurements 6 weeks apart, at any point in the past; and

- CD4 cell count < 300 cells/microL (within 90 days prior to day 0, outside labs
will be accepted).

- If patient has documented ICL as defined in i. and is currently enrolled in NIH
ICL natural history protocol (EPIC 09-I-0102) a CD4 cell count < 300 cells/ L
(within 18 months of day 0) is sufficient for enrollment.

- Healthy volunteers must have:

- CD4 cell count of greater than or equal to 450 cells/MicroL (within 90 days prior
to day 0, outside labs will be accepted).

EXCLUSION CRITERIA:

1. Prior receipt of GARDASIL 9 (Receipt of 2-valent and 4-valent versions of vaccine is
not exclusionary).

2. Pregnancy or breastfeeding.

3. History of hypersensitivity, including severe reactions to yeast or other component of
the vaccine or to a previous vaccination with another GARDASIL vaccine.

4. HIV infection or any other recognized congenital or acquired immunodeficiency (i.e.,
SCID IL-2/JAK3/ADA, MAGT1, MHC1 deficiency, DOCK8, etc).

5. Current moderate or severe acute illness (i.e., febrile illness, seizure, myocardial
infarction, cerebrovascular accident, pulmonary embolism) that in the opinion of the
PI, would make the subject unsuitable for the study.

6. Serum creatinine > 1.5 times upper limit of normal, platelets < 100,0000/mm3,
hemoglobin < 9 g/dL, or AST/ALT > 2 times upper limit of normal, immunoglobulin G
level < 450 mg/liter.

7. Current use of systemic glucocorticosteroids or immunomodulants, other than
corticosteroid nasal spray or inhaler and topical steroids, which are not
exclusionary.

8. Any cancer diagnosis or autoimmune condition requiring systemic chemotherapy or
immunomodulant affecting antibody responses (i.e., rituximab, ibrutinib etc.),
intravenous or subcutaneous immunoglobulin supplementation, radiation therapy, or
immunomodulatory treatment within the previous 6 months (presence of precancerous
lesions is not exclusionary

9. Receipt of an investigational vaccine within 2 weeks of day 0.

10. Receipt of ACIP recommended immunizations within 1 week of day 0.

11. Any condition that, in the opinion of the investigator, contraindicates participation
in this study.