VRC 313: A Trivalent Virus-like Particle (VLP) Encephalitis Vaccine (WEVEE) in Healthy Adults

This is a Phase 1, randomized, open-label, dose-escalation study to examine the safety, tolerability, and immune response of three doses (6 mcg, 30 mcg, and 60 mcg) of the WEVEE vaccine (VRC-WEVVLP073-00-VP) alone or with alum adjuvant (VRC-GENMIX083-AL-VP) in a 2-product administration regimen.

Eligible subjects were randomized to WEVEE alone (Groups 1, 3, and 5) or WEVEE plus alum (Groups 2, 4, and 6, respectively) in each dose group. No more than 1 subject was randomized and vaccinated per day for the first 3 subjects at each dose. If the 6 mcg dose of WEVEE was assessed as not showing safety concerns by a Protocol Safety Review Team (PSRT), randomization began for Groups 3 and 4 (30 mcg WEVEE without alum and with alum, respectively). In a second safety review conducted on the first 3 subjects to receive 30 mcg, if the 30 mcg dose of WEVEE was assessed as not showing safety concerns by the PSRT, randomization began for Groups 5 and 6 (60 mcg WEVEE without and with alum, respectively).

The product was administered in the upper arm muscle as an intramuscular (IM) injection via needle and syringe at Day 0 and 8 weeks later.

For all groups, solicited reactogenicity was evaluated using a 7-day diary card. Assessment of vaccine safety included clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.

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.