Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults

Participants 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. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Local Symptom is the number of participants 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 H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=25).

Participants 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. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of participants 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 H10ssF-6473 product administration, at approximately Week 1 and at approximately Week 17

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=25).

Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete Blood Count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at Day 14, 28, and 280 (Group 1) or at Day 14, 28, 112, 140 and 280 (Groups 2A-2B). Iron and serum ferritin were collected at Day 28 (Group 1) or at Days 112 and 140 (Groups 2A-2B). Creatinine results were collected at Day 14 (Group 1) or at Days 14 and 140 (Groups 2A-2B). Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.

Time frame: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

Population: Population included all enrolled participants who had laboratory results available at any study visit post product administration. If several cases of the same type of abnormal lab value/AE were detected in a participant, the participant was counted one time at the highest severity.

Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit. ILI was defined as fever (temperature of 100 degrees F \[37.8 degrees C\] or greater) and a cough and/or sore throat in the absence of a known cause other than influenza. Collection of nasopharyngeal swabs were used for laboratory confirmation of influenza by polymerase chain reaction (PCR) in participants who met criteria for ILI. Subsequently, results of any reported laboratory testing for identification of pathogens were included for cases meeting initial criteria for ILI. The severity of illness in participants with laboratory confirmed influenza illness were captured on a case report form rather than on an Adverse Event (AE) form.

Time frame: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection (N=25).

New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 40. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection (N=25).

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), influenza-like illness (ILI) or influenza and new chronic medical conditions that required ongoing medical management (reported as separate outcomes) 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 participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks after each H10ssF-6473 product administration, up to Week 20

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection (N=25).

SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 40. 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 participant with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 after H10ssF-6473 product administration through the study participation, up to Week 40

Population: Population included all enrolled participants who received at least one H10ssF-6473 study injection (N=25).

Stem-specific H10ss antibody titers were measured by Electrochemiluminescence Assay (ECLIA) using a Meso Scale Discovery (MSD) platform. Serum samples collected at baseline and at 2 weeks after the single and/or last product administration were tested in the assay. Area under the curve (AUC) was calculated for each serum sample tested in the 8-fold serial dilutions. The AUC measurement is calculated for each single timepoint sample (baseline, week 2: 2 weeks after the single vaccination and week 18: 2 weeks after the final vaccination). The AUC is calculated with GraphPad Prism™ using the trapezoid rule from the raw sample response (ECL response) over an 8-fold dilution series (dilution factor) for each sample. Group geometric mean AUCs and 95% Confidence Intervals are reported.

Time frame: Baseline to 2 weeks after the single or first injection, at Week 2 and from Week 16 to 2 weeks after the second injection, at Week 18

Population: Baseline and Week 2 analyses included all who received at least one H10ssF-6473 study injection for which samples were available (N=25). Week 18 analysis included all who received two H10ssF-6473 injections for which samples were available (N=22).