Chikungunya Virus Vaccine Trial in Healthy Adults

This is a Phase I, open-label, dose-escalation study to examine the safety, tolerability,
and immune response to a Virus-Like Particle (VLP) Chikungunya Virus (CHIKV) vaccine in
healthy adults ages 18 to 50 years old. The plan is for 25 subjects to receive 3
intramuscular vaccine injections at weeks 0, 4, and 20. The three groups will be enrolled
sequentially starting with the lowest dose of 10 micrograms per injection in Group 1.

The hypothesis is that the vaccine is safe and induces immune responses to CHIKV. The
primary objective is to evaluate the safety and tolerability of the investigational vaccine,
VRC-CHKVLP059-00-VP, at three dosages, 10 micrograms (mcg), 20 mcg, and 40 mcg, in healthy
adults. The secondary objective is to evaluate the antibody response against CHIKV VLPs four
weeks after the third vaccine injection. The exploratory objectives relate to
antigen-specific humoral and cellular immune responses throughout the study.

INCLUSION CRITERIA:

A participant must meet all of the following criteria:

1. 18 to 50 years old

2. Available for clinical follow-up through Week 44

3. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process

4. Complete an Assessment of Understanding prior to enrollment and verbalize
understanding of all questions answered incorrectly

5. Able and willing to complete the informed consent process

6. Willing to donate blood for sample storage to be used for future research

7. In good general health, with a BMI less than or equal to 40, without clinically
significant medical history, and has satisfactorily completed screening

8. Physical examination and laboratory results without clinically significant findings
within the 56 days prior to enrollment

Laboratory Criteria within 56 days prior to enrollment:

9. Hemoglobin greater than or equal to11.5 g/dL for women; greater than or equal to13.5
g/dL for men

10. WBC: 3,000-12,000 cells/mm(3).

11. Differential either within institutional normal range or accompanied by physician
approval

12. Total lymphocyte count: greater than or equal to 800 cells/mm(3)

13. Platelets = 125,000-500,000/mm(3)

14. Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal
range

15. Serum creatinine less than or equal to1x upper limit of normal (less than or equal
to1.3 mg/dL for females; less than or equal to1.4 mg/dL for males).

16. Negative FDA-approved HIV blood test

Female-Specific Criteria

17. Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women
presumed to be of reproductive potential

18. A woman of childbearing potential must agree to use an effective means of birth
control from at least 21 days prior to enrollment through 12 weeks after last study
vaccination

EXCLUSION CRITERIA:

A participant will be excluded if one or more of the following conditions apply:

Female-Specific Criteria

1. Woman who is breast-feeding or planning to become pregnant during the time projected
for individual study participation

2. Systemic immunosuppressive medications or cytotoxic medications within 12 weeks prior
to enrollment [with the exceptions that a short course of corticosteroids (less than
or equal to10 days duration or a single injection) for a self-limited condition at
least 2 weeks prior to enrollment will not exclude study participation]

3. Blood products within 16 weeks prior to enrollment

4. Immunoglobulin within 8 weeks prior to enrollment

5. Prior vaccinations with an investigational CHIKV vaccine

6. Investigational research agents within 4 weeks prior to enrollment

7. Live attenuated vaccines within 4 weeks prior to enrollment

8. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or
allergy treatment with antigen injections, within 2 weeks prior to enrollment

9. Current anti-TB prophylaxis or therapy

Subject has a history of any of the following clinically significant conditions:

10. A history of confirmed or suspected CHIKV infection

11. A history of immune-mediated or clinically significant arthritis

12. Serious reactions to vaccines that preclude receipt of study vaccinations as
determined by the investigator

13. Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of
angioedema

14. Asthma that is unstable or required emergent care, urgent care, hospitalization or
intubation during the past two years or that is expected to require the use of oral
or intravenous corticosteroids

15. Diabetes mellitus (type I or II), with the exception of gestational diabetes

16. Idiopathic urticaria within the past year

17. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
platelet disorder requiring special precautions) or significant bruising or bleeding
difficulties with IM injections or blood draws

18. Malignancy that is active, or treated malignancy for which there is not reasonable
assurance of sustained cure, or malignancy that is likely to recur during the period
of the study

19. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol
withdrawal more than 3 years ago, or 3) seizures that have not required treatment
within the last 3 years

20. Asplenia, functional asplenia or any condition resulting in the absence or removal of
the spleen

21. Psychiatric condition that may preclude compliance with the protocol; past or present
psychoses; disorder requiring lithium; or within five years prior to enrollment, a
history of suicide plan or attempt

22. Any medical condition (such as thyroid disease or hypertension that are not well
controlled by medication, or viral hepatitis) that, in the judgment of the
investigator, is a contraindication to protocol participation or impairs a
volunteer's ability to give informed consent