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

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for Any Local Symptom is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).

Time frame: 7 days after each product administration, at approximately Week 1 and Week 9

Population: Population included all enrolled subjects who received at least one study injection and provided safety data (via diary card and/or laboratory results) following the injection.

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).

Time frame: 7 days after each product administration, at approximately Week 1 and Week 9

Population: Population included all enrolled subjects who received at least one study injection and provided safety data (via diary card and/or laboratory results) following the injection.

Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hemoglobin change from baseline, hematocrit, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC), differential, platelet, and ALT results were collected at screening (≤ 28 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 56, 70, 84, 168 and 252. Creatinine results were collected at screening, Day 0 and Day 56. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (modified from FDA Guidance, September 2007) were used.

Time frame: Day 0 through Day 252

Population: Population included all enrolled subjects who had laboratory results available at any study visit post baseline.

Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks of each study product administration, up to Week 12

Population: Population included all enrolled subjects who received at least one study injection and provided safety data (via diary card and/or laboratory results) following the injection.

SAEs were reported from receipt of first study product administration through the last expected study visit at Day 252. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through Day 252

Population: Population included all enrolled subjects who received at least one study injection and provided safety data (via diary card and/or laboratory results) following the injection.

WEVEE antigen-specific antibody responses as evaluated by virus-specific neutralization assays. Eastern Equine Encephalitis Virus (EEEV), Venezuelan Equine Encephalitis Virus (VEEV) and Western Equine Encephalitis Virus (WEEV) neutralizing titers were assessed using a plaque reduction neutralization test (PRNT) at baseline and 4 weeks after the second study injection. Geometric mean titers of the individual PRNT80 (80% plaque reduction neutralization) titer values are reported.

Time frame: 4 weeks after the last product administration, at Week 12

Population: Subjects who received 2 study injections per protocol. One Group 1 subject received only one injection due to an unrelated AE of Neutropenia.

A subject was a responder or met the threshold of a positive response if the post vaccination anti-Eastern Equine Encephalitis Virus (EEEV), Venezuelan Equine Encephalitis Virus (VEEV) or Western Equine Encephalitis Virus (WEEV) antibody titer was 10 or greater.

Time frame: 4 weeks after the last product administration, at Week 12

Population: Subjects who received 2 study injections per protocol. One Group 1 subject received only one injection due to an unrelated AE of Neutropenia.