VRC 313: A Trivalent Virus-like Particle (VLP) Encephalitis Vaccine (WEVEE) in Healthy Adults
Condition: Venezuelan Equine Encephalitis; Western Equine Encephalitis; Eastern Equine Encephalitis; Alphavirus Infections
MeSH terms: Encephalomyelitis, Equine; Encephalomyelitis, Venezuelan Equine; Encephalomyelitis, Eastern Equine; Encephalomyelitis, Western Equine; Alphavirus Infections; Encephalitis
Intervention: VRC-WEVVLP073-00-VP; VRC-GENMIX083-AL-VP
Intervention description: VRC-WEVVLP073-00-VP is composed of 1:1:1 ratio of WEE, EEE, and VEE virus-like particles (VLP); VRC-GENMIX083-AL-VP is an adjuvant
Intervention MeSH terms: Aluminum Hydroxide
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Subjects were randomized into:
WEVEE vaccine alone (Group 1, Group 3, and Group 5) or, WEVEE vaccine mixed with alum (Group 2, Group 4, and Group 6, respectively).
The study started by randomizing subjects to get a dose of 6 mcg in Group 1 or Group 2. Safety data were reviewed after 2 weeks to make sure this vaccine dose had no safety concerns before subjects were randomized to get the next dose of 30 mcg in Group 3 or Group 4. Safety data were reviewed again to make sure the 30 mcg vaccine dose had no safety concerns before subjects were randomized to the 60 mcg dose in Group 5 or Group 6.
A total of 30 subjects were randomized among the 6 groups.
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Alphavirus; VEE; WEE; EEE; Vaccine; Virus-like particles

Summary:

      Western Equine Encephalitis Virus (WEEV), Eastern Equine Encephalitis Virus (EEEV), and
      Venezuelan Equine Encephalitis Virus (VEEV) are transmitted to humans by infected mosquitoes
      and can cause encephalitis (swelling of the brain) and other neurological manifestations,
      including fever, chills, discomfort, feeling sick, muscle pain and then headache, vomiting,
      restlessness, irritability, seizures, coma, and death.

      Vaccines teach the body to prevent or fight an infection. When the body learns to fight an
      infection, this is called an immune response. Researchers developed a vaccine against
      Western, Eastern and Venezuelan equine encephalitis viruses to help the body make an immune
      response. There are no live or killed viruses in the vaccine, so you cannot get infected with
      any of these 3 viruses from getting the vaccine.

      The experimental trivalent encephalitis vaccine, VRC-WEVVLP073-00-VP, is composed of Western
      equine encephalitis (WEE), Eastern equine encephalitis (EEE), and Venezuelan equine
      encephalitis (VEE) virus-like particles (VLP).

      The purpose of this study is to test three doses (6 mcg, 30 mcg, and 60 mcg) of this
      experimental vaccine against Western, Eastern and Venezuelan equine encephalitis viruses.
    

Eligibility criteria:

        Inclusion Criteria:

        A volunteer must have met all of the following criteria:

          -  Age 18 to 50 years

          -  Available for clinical follow-up through 36 weeks after randomization

          -  Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process

          -  Able and willing to complete the informed consent process

          -  Willing to donate blood for sample storage to be used for future research

          -  In good general health, without clinically significant medical history, and has
             satisfactorily completed screening

          -  Physical examination and laboratory results without clinically significant findings
             within the 28 days prior to randomization

        Laboratory Criteria within 28 days prior to randomization:

          -  Hemoglobin within institutional normal range or accompanied by Principal Investigator
             (PI) or designee approval

          -  White blood cell (WBC) and differential either within institutional normal range or
             accompanied by PI or designee approval

          -  Total lymphocyte count: ≥800 cells/mm3

          -  Platelets: 125,000-500,000/mm3

          -  Alanine aminotransferase (ALT): ≤ 1.25 x upper limit of normal range

          -  Serum creatinine: ≤1.1 x upper limit of normal

          -  Negative for HIV infection by an FDA-approved method of detection

        Criteria applicable to women of childbearing potential:

          -  Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on
             day of randomization before receiving the study product

          -  Agrees to use an effective method of birth control, if sexually active, from at least
             21 days prior to randomization through the last study visit.

        Exclusion Criteria:

        A volunteer was excluded if one or more of the following conditions applied:

        Female-Specific Criteria

        • Breast-feeding or planning to become pregnant while participating in the study

        Volunteer received any of the following:

          -  More than 10 days of systemic immunosuppressive medications or cytotoxic medications
             within the 4 weeks prior to randomization or any within the 14 days prior to
             randomization

          -  Blood products within 16 weeks prior to randomization

          -  Immunoglobulin within 8 weeks prior to randomization

          -  Prior vaccinations with an investigational alphavirus vaccine

          -  Investigational research agents within 4 weeks prior to randomization or planning to
             receive investigational products while on study

          -  Live attenuated vaccines within 4 weeks prior to randomization

          -  Inactivated vaccines within 2 weeks prior initial study vaccine administration unless
             approved by the PI

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

        Volunteer has a history of any of the following clinically significant conditions:

          -  A history of confirmed or suspected viral encephalitis infection

          -  Serious reactions to vaccines that preclude receipt of study vaccinations as
             determined by the investigator

          -  Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

          -  Asthma that is not well controlled

          -  Diabetes mellitus (type I or type II) with the exception of gestational diabetes

          -  Thyroid disease that is not well controlled

          -  Hypertension that is not well controlled

          -  Evidence of autoimmune disease or immunodeficiency

          -  Idiopathic urticaria within the last year

          -  Malignancy that is active or history of malignancy that is likely to recur during the
             study

          -  Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with intramuscular (IM) product administration or blood draws

          -  Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol
             withdrawal more than 3 years ago, or 3) seizures or treatment for a seizure disorder
             within the last 3 years

          -  Asplenia, functional asplenia or any condition resulting in absence or removal of the
             spleen

          -  Psychiatric condition that precludes compliance with the protocol; past or present
             psychoses; or within 5 years prior to randomization, a history of suicide plan or
             attempt

          -  Any other chronic or clinically significant medical, psychiatric or social condition
             that, in the judgement of the investigator is a contraindication to protocol
             participation or impairs a volunteer's ability to give informed consent.