Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome
Condition: Autosomal-dominant Hyper-IgE Syndrome
MeSH terms: Job Syndrome; Syndrome
Intervention: NDV-3A
Intervention description: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: AD-HIES; Anti-rAls3 Antibody; Staphylococcus Aureus; Candida Albicans; RNA Transcriptome

Summary:

      Background:

      AD-HIES is a disease that weakens the immune system. It puts people at risk for infections,
      particularly Staph and Candida infections. Researchers want to test a vaccine that may help
      keep people from getting these infections, which would help people with AD-HIES.

      Objective:

      To test the new vaccine NDV-3A for protection against infection from the yeast Candida and
      the bacterium Staphylococcus aureus (Staph).

      Eligibility:

      Adults ages 18-55 who have AD-HIES

      Healthy volunteers ages 18-55

      Design:

      Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone
      in between some visits.

      Participants will be screened with a medical history, physical exam, and blood and urine
      tests.

      Participants will have 2 baseline visits. They will have repeat the screening tests. They
      will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected.
      Vaginal and stool samples are optional. Any eczema on their skin will be looked at.

      Participants will fill out symptom diary cards to record how they feel.

      Participants will have the NDV-3A vaccine injected into a muscle in the arm.

      Participants will return the next 2 days. They will have a physical exam. Blood will be
      collected.

      Participants will have 2 more follow-up visits at the NIH. They will have a physical exam.
      They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected.
      Vaginal and stool samples are optional.

      Participants will be called once a month for 5 months after the vaccination. There is an
      optional visit about 6 weeks after the vaccination. Participants will provide a blood sample
      at this visit.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age 18-55 years.

               2. For healthy volunteers: in general good health, without significant medical
                  illness, physical exam findings, or significant laboratory abnormalities as
                  determined by the investigator.

               3. For participants with AD-HIES: confirmation of diagnosis with a STAT3 mutation.

               4. Participants who can get pregnant must be willing to use an acceptable form of
                  contraception for the duration of participation and have a negative pregnancy
                  test at screening.

               5. Agree to allow storage of biological samples for future research.

        EXCLUSION CRITERIA:

          1. Has a history of allergic response or other serious reaction to aluminum and/or yeast
             products.

          2. Has a history of clinically significant allergy including anaphylaxis or other serious
             reaction to food, vaccines, or other drugs, that in the opinion of the investigator,
             might put the participant at undue risk.

          3. Has an active infection (such as S aureus abscess, pneumonia, acute Candida
             mucocutaneous infection). Baseline state of chronic infections will be considered by
             the PI (eg, chronic Pseudomonas infection in lung).

          4. Has an active infection with hepatitis B, hepatitis C, or HIV.

          5. Has received or is planning to receive any investigational drug, investigational
             vaccine, or investigational device within four weeks prior to vaccination, or at any
             other time during their participation in the study.

          6. Has received or is planning to receive any other live vaccine within three weeks
             before vaccination or for three weeks after vaccination.

          7. Self-reported current alcohol abuse or addiction.

          8. Self-reported current illicit drug abuse or addiction, or drug screen positive for
             illicit drugs.

          9. Current or planned use, within 3 weeks before vaccination, of any medications or
             treatments that may alter immune responses to the study vaccine (eg, immunosuppressive
             medications including systemic corticosteroids, cyclosporine, tacrolimus, cytotoxic
             drugs, Bacillus Calmette-Guerin, monoclonal antibodies, or radiation therapy).
             Topical, intranasal, or inhaled immunosuppressants such as corticosteroids will be
             allowed.

         10. Current or planned use within 2 weeks before vaccination of immune globulin
             replacement.

         11. Has any of the following laboratory abnormalities at the screening visit:

               1. Alanine transaminase (ALT), aspartate transaminase (AST), and/or alkaline

                  phosphatase (ALP) > 1.5 times the upper limit of normal (ULN).

               2. Total bilirubin level > 1.5 times the ULN

               3. Serum creatinine level > 1.5 times the ULN

               4. Absolute neutrophil count < 750 cells/microliter

               5. Hemoglobin < 9 mg/dL

               6. Platelet count < 100,000

         12. Refusal or inability to comply with study procedures to the extent that it is
             potentially harmful to the participant or to the integrity of the study data.

         13. Has donated blood/plasma within four weeks before vaccination.

         14. Is pregnant or breastfeeding, or intends to become pregnant over the course of the
             study.

         15. Is unable to commit to the follow-up visits and or has unreliable access to a
             telephone for follow-up contacts, either by self-admission (self-reporting) or in the
             opinion of the investigator.

         16. Any other condition the investigator believes would interfere with the participant s
             ability to provide informed consent, comply with study instructions, or that might
             confound the interpretation of the study results or put the participant at undue risk.