Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 Omicron-specific , monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3.
Omicron variants, although more infective, are associated with lower rates of hospitalization and death compared with previous SARS-CoV-2 strains. Studies have shown that the intrinsic severity of the Omicron variant is similar to that of its predecessors and cross-reactive protection from vaccination and/or infection plays an important role in reducing the severity of Omicron-associated COVID-19 exhibited a more than 50% decrease in T cell reactivity to the Omicron spike.
The platform used to develop GEMCOVAC-OM has certain advantages over the other mRNA vaccines approved for COVID-19. GEMCOVAC-OM is administered intradermally using a needle-free injection system called Tropis. The dermis has a rich network of dendritic cells, macrophages and T cells. Additionally, the absence of a needle obviates challenges of need for sharps disposal, needle-stick injuries, cross-contamination and needle phobia.
In phase 3, consecutive 420 in the immunogenicity cohort were randomized in a 2:1 ratio into GEMCOVAC-OM and ChAdOx1 nCoV-19 by stratified block randomization through the IWRS. A randomization code was assigned to each participant in sequence in the order of enrollment, and then the participants received the investigational products labeled with the same code. This was an open-label study, and no masking was performed.
Participants were provided an e-diary or a paper diary to record the solicited AEs till day 7 and unsolicited AEs as well as concomitant medication taken, if any, till the end of the study. A telephone call was placed to all the participants at day 7 to record any additional AEs, if any. Participants visited the study site for visit 2 , visit 3 and visit 4 . Blood for assessing immunogenicity was drawn at visit 1 before vaccination , day 29 and day 90.
PBMCs were isolated using BD Vacutainer CPT with sodium citrate tubes following the manufacturer’s guidelines and subsequently cryopreserved in liquid nitrogen. For immune-phenotyping purposes, frozen PBMCs were thawed and allowed to rest in complete RPMI 1640 culture medium supplemented with 10% FBS, 100 U mlstreptomycin for 18–22 h. Gating strategies for both T cell and B cell experiments are given in Extended Data Fig..