GRAd-COV2, a gorilla adenovirus based candidate vaccine against COVID-19, is safe and immunogenic in young and older adults

Safe and effective vaccines against coronavirus disease 2019 (COVID-19) are urgently needed to control the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand. We have developed a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized pre-fusion SARS-CoV-2 Spike protein, named GRAd-COV2. We aimed to assess the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. To this purpose, a phase 1, dose-escalation, open-label trial was conducted including 90 healthy subjects, (45 aged 18-55 years and 45 aged 65-85 years), who received a single intramuscular administration of GRAd-CoV2 at three escalating doses. Local and systemic adverse reactions were mostly mild or moderate and of short duration, and no serious AE was reported. Four weeks after vaccination, seroconversion to Spike/RBD was achieved in 43/44 young volunteers and in 45/45 older subjects. Consistently, neutralizing antibodies were detected in 42/44 younger age and 45/45 older age volunteers. In addition, GRAd-COV2 induced a robust and Th1-skewed T cell response against the S antigen in 89/90 subjects from both age groups. Overall, the safety and immunogenicity data from the phase 1 trial support further development of this vaccine. One Sentence Summary GRAd-COV2, a candidate vaccine for COVID-19 based on a novel gorilla adenovirus, is safe and immunogenic in younger and older adults ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: SCa, RC, FM, VA, FG, FN, MS, SB, ASo, AMC, FB, MG, AR, AV, SCo and AF are employees of ReiThera Srl. AF and SCo are also shareholders of Keires AG. SCo, AR, and AV are inventors of the Patent Application No. 20183515.4 titled GORILLA ADENOVIRUS NUCLEIC ACID- AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF. All remaining authors declare that they have no competing interests. ### Clinical Trial NCT04791423 ### Funding Statement The phase 1 study has been funded by Regione Lazio and Italian Ministry of research. INMI authors are supported by the Italian Ministry of Health (Ricerca Corrente line 1, COVID-2020-12371735 and COVID-2020- 12371817) ### 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 study was conducted according to the Declaration of Helsinki, and approved by the Italian Regulatory Drug Agency (AIFA) and the Italian National Ethical Committee for COVID-19 clinical studies. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 Full dataset can be required and will be availbale on request by 1 year after the end of the study