COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

This phase 2 clinical trial will evaluate the safety and immunogenicity of additionaldoses of prototype and variant (alone or in combination) vaccine candidates in previouslyvaccinated participants with or without prior severe acute respiratory syndromecoronavirus 2 (SARS‐CoV‐2) infection and will evaluate innate, cellular, and humoralimmune responses to inform on how to shift the immune response to cover new variants asthey emerge. A randomized open‐label, non‐placebo controlled, multi‐site, multi‐stageclinical trial in individuals, 18 years of age and older, who are in a stable state ofhealth, has received a complete authorized/approved vaccine series (primary series +booster either with homologous or heterologous vaccine products) >/= 16 weeks prior toenrollment. Subjects will be stratified by i) age (18‐64 years and = 65 years of age)(however arms 16 and 17 or stage 4 will only enroll participants between the ages of18‐49 years) and ii) history of confirmed prior SARS‐CoV‐2 infection, and randomlyassigned to receive one of several variant vaccines. Enrollment will target a goal ofapproximately 45% of each of the variant vaccine arms to be in older adults (= 65 yearsof age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID‐19 forall 4 stages. This is an adaptive design and may add arms of new vaccine platforms and/orvariant lineage spike vaccines as needed. The study arms will be conducted in differentstages (that could overlap) depending on public health needs and the availability ofstudy products (starting with the available mRNA vaccines). The primary objective is toevaluate humoral immune responses of candidate SARS‐CoV‐2 variant vaccines, alone or incombination. The secondary objective is to evaluate the safety of candidate SARS‐CoV‐2variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 daysfollowing each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended AdverseEvents (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical(NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12months after last vaccine dose.