GRAd-COV2 vaccine provides potent and durable immunity in randomised placebo-controlled phase 2 trial (COVITAR)

Background SARS-CoV-2 ongoing pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccines portfolio. We report safety and immunogenicity of GRAd-COV2, a novel gorilla adenovirus-based COVID-19 vaccine, in a phase 2 trial aimed at identifying the appropriate dose and schedule. Method 917 eligible adults aged 18 years or older, including participants with co-morbidities, were randomised to receive, 21 days apart, a single vaccine administration at 2×1011 viral particles (vp) followed by placebo, or repeated vaccine administration at 1×1011 vp, or two doses of placebo. Primary endpoints were the incidence of local and systemic solicited AEs for 7 days post each dose and the post-treatment (35 days after the first dose), geometric mean titers (GMTs) and geometric mean fold rise (GMFRs) of ELISA antibody responses to Spike protein. Additional humoral and cellular immune response parameters were monitored for up to six months. Results The safety profile of GRAd-COV2 was characterized by short-term, mild-to-moderate pain and tenderness at injection site, fatigue, headache, malaise, and myalgia. Neither related SAEs nor deaths were reported. Humoral (binding and neutralizing) Ab responses peaked at day 35 after a single administration, were boosted by a second vaccination, were sustained until day 57 to then decline at day 180. Potent, VOC cross-reactive T cell responses peaked already after first dose with high frequencies of long-lived CD8 T cells. Conclusion GRAd-COV2 was safe, and induced robust immune responses after a single immunization; the second administration increased humoral but not cellular immune responses. Trial Registration [ClinicalTrials.gov][1] [NCT04791423][2]. Funding ReiThera Srl ### Competing Interest Statement SCapo, RCam, RD, FG, SBa, AMC, GP, SCo AF are full employees of ReiThera Srl. SCo and AF are shareholders of Keires AG. SCo is named inventor of the Patent Application No. 20183515.4 titled GORILLA ADENOVIRUS NUCLEIC ACID- AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF. LV is full employee of Exom, the CRO in charge of the COVITAR study management. SLC received honoraria from Gilead, ViiV, GSK, Janssen, MSD, has participated to the Advisory Board of Gilead, ViiV, GSK, Janssen, MSD and received support for attending meetings from Gilead. MLic received honoraria and support for attending meetings from Gilead, MSD, ViiV, participated to Advisory Boards of ViiV, Abbvie and MSD, and received grants through the institution from Gilead and Abbvie. RCar was member of the COVITAR study steering committee. CI received financial support from Exom for statistical analysis of COVITAR study. ### Clinical Trial Clinical trial ID# [NCT04791423][2] ### Funding Statement This study was funded by ReiThera srl ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the Italian COVID national Ethics Committee (Lazzaro Spallanzani Institute), and the local Ethics Committees of the other 23 clinical centers gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04791423&atom=%2Fmedrxiv%2Fearly%2F2022%2F10%2F10%2F2022.10.08.22280836.atom