GRAd-COV2 gorilla adenovirus based candidate vax against COVID-19 safe, immunogenic in young, older adults

 Simone Lanini, Stefania Capone, Andrea Antinori, Stefano Milleri, Emanuele Nicastri, Roberto Camerini, Chiara Agrati, Concetta Castilletti, Federica Mori, Alessandra Sacchi, Giulia Matusali, Roberta Gagliardini, Virginia Ammendola, Eleonora Cimini, Fabiana Grazioli, Laura Scorzolini, Federico Napolitano, Maria Maddalena Plazzi, Marco Soriani, Aldo De Luca, Simone Battella, Andrea Sommella, Alessandra Maria Contino, Federica Barra, Michela Gentile, Angelo Raggioli, Youfang Shi, Enrico Girardi, Markus Maeurer, Maria Rosaria Capobianchi, Francesco Vaia, Mauro Piacentini, Guido Kroemer, Alessandra Vitelli, Stefano Colloca, Antonella Folgori, Giuseppe Ippolito

doi: https://doi.org/10.1101/2021.04.10.21255202

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.10.21255202v1.full.pdf

Abstract

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.

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)

https://www.medrxiv.org/content/10.1101/2021.04.10.21255202v1