Recombinant Influenza Vaccine Versus Standard Egg-Based Inactivated Influenza Vaccine in Adults 18-64 Years

This randomized, active comparator trial will compare the clinical efficacy of recombinant influenza vaccine (RIV) to standard-dose egg-based inactivated influenza vaccine (SD IIV) among adults aged 18-64 years. The primary study hypothesis is that the clinical efficacy of RIV is superior to that of SD IIV to prevent and attenuate influenza-like illness (ILI)-associated influenza virus infection. Relative efficacy will be assessed by comparing rates of ILI-associated reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza virus infection and measures of infection and illness attenuation among participants who receive RIV versus SD IIV. A secondary hypothesis is that humoral and cell-mediated immune responses to RIV are superior to responses to SD IIV. Relative immunogenicity will be assessed by comparing markers of humoral and cell-mediated immune responses post-vaccination among a subset of participants who receive RIV versus SD IIV.

Inclusion Criteria: * Aged 18-64 years * Comfortable reading and responding to text messages or emails sent in either English, Spanish, or Chinese * Currently enrolled as a student in a college or graduate degree program AND attending in-person classes with other students. OR Currently employed as a frontline worker defined as an occupation that cannot be done from home or alone AND have direct face-to-face contact, defined as being within 6 feet, or about two arms' lengths, with co-workers, patients or the public as part of full-time (at least 20 hours per week) job responsibilities. * Have daily access to the internet and a mobile phone that can send and receive text messages. * Plan to continue to live/work in the study area through May 2023 (if trial season 1) or May 2024 (if trial season 2). For students in college or graduate degree programs, this is defined as living/working in the area excluding brief absences during school vacation periods. Exclusion Criteria: * Lives with another person who is already enrolled in this study as reported by the subject. * Previous hypersensitivity reaction to the study vaccines as reported by the subject. * Has already received current year influenza vaccine on our after July 1, 2022 as reported by the subject.