Safety and Immunogenicity of the Bris10 M2SR and Sing2016 M2SR H3N2 Monovalent Influenza Vaccines

This is a Phase I double-blind, randomized, placebo-controlled study in 250 healthy adults, 18-49 years of age, inclusive, who are in good health and meet all eligibility criteria. This dose escalation clinical study is designed to assess the safety, tolerability/reactogenicity, and immunogenicity of H3N2 M2SR investigational vaccines for prevention of influenza, when delivered at increasing dosages or in two doses. Subjects will be enrolled in five groups in a 1:1:1:1:1 ratio. Arm 1 will receive a low dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 2 will receive a medium dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 3 will receive a high dose of Sing2016 M2SR intranasally on days 1 and 29. Arm 4 will receive a low dose of Bris16 M2SR intranasally on days 1 and 29. Arm 5 will receive a placebo intranasally on days 1 and 29. Study duration will be approximately 8 months with subject participation duration approximately 7 months. The primary study objective is to assess the safety and reactogenicity of a monovalent live single replication influenza H3N2 M2SR vaccine. The secondary study objectives are to evaluate systemic and mucosal immune responses induced by H3N2 M2SR vaccination.

Inclusion criteria

• Give written informed consent to participate.
• Age 18 - 49 years old.
• Judged suitable by the PI, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations.
• Willing to use oral, implantable, transdermal or injectable contraceptives, or sexual abstinence, from screening and until 28 days after second vaccine dose.
• Willing to adhere to the requirements of the study and willing and able to communicate with the Investigator and understand the requirements of the study.

Exclusion criteria

• Abnormal screening hematology or chemistry value per the FDA Toxicity Guidance.
• Pulse rate or blood pressure outside the reference range for this study population and considered as clinically significant by the Investigator.
• Has an acute or chronic medical condition or history of a medical condition that, in the opinion of the Investigator, would render the study procedures unsafe or would interfere with the evaluation of the responses.
• Presence or clinically significant history of lung disease, asthma, chronic obstructive pulmonary disease (COPD), or otherwise poor lung function.
• Any confirmed or suspected immunosuppressive or immunodeficient state.
• Presence of household member or close personal or professional (i.e., healthcare worker) who is a child under one year of age; is pregnant; has known immunodeficiency or is receiving immunosuppressant medication; is undergoing or soon to undergo cancer chemotherapy; has been diagnosed with emphysema, COPD, or other severe lung disease and resides in a nursing home; and/or has received a bone marrow or solid organ transplant.
• Females who are pregnant or lactating.
• Acute febrile illness within 72 hours prior to vaccination.
• Any condition, in the opinion of the Investigator, (such as subjects who have medically high-risk conditions) that might interfere with the primary study objectives for safety of the study subject.