Non-Clinical Safety of GRAd Vector-Based COVID-19 and HIV Vaccines Supports a Platform Regulatory Approach
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vaccines-14-00157.pdf
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Author(s)
Paalangara, Reji
Gohin, Stephanie
Menard, Alexis
Amy, Charlotte
Berrabah, Wahiba
Rogue, Alexandra
Getz, Matthew A.
Alrubayyi, Aljawharah
Battella, Simone
Raggioli, Angelo
Date Issued
February 6, 2026
Journal
Vaccines
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Paalangara, Reji, Stephanie Gohin, Alexis Menard, Charlotte Amy, Wahiba Berrabah, Alexandra Rogue, Matthew A. Getz, Aljawharah Alrubayyi, Simone Battella, Angelo Raggioli, and et al. 2026. "Non-Clinical Safety of GRAd Vector-Based COVID-19 and HIV Vaccines Supports a Platform Regulatory Approach" Vaccines 14, no. 2: 157.
Version
Final published version
Abstract
Background/Objectives: The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. With the aim to provide scientific evidence supporting a “vaccine platform approach”, here we present the complete non-clinical studies for two investigational vaccines, GRAd-COV2 and GRAdHIVNE1, based on GRAd, a gorilla-derived group C adenoviral vector. Methods: The biodistribution of GRAd genomes following the intramuscular administration of the vaccines was assessed in rats by a sensitive qPCR method. Local tolerance and systemic toxic effects were evaluated in single- and repeated-dose toxicity studies in rabbits. Results: GRAd-COV2 and GRAdHIVNE1 were well-tolerated. Distribution was highly confined to the injection site and draining lymph nodes, and toxicity profile consisted of transient, non-adverse inflammatory responses, while the expected immune responses to the encoded antigens were successfully induced. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. Conclusions: The established non-clinical safety profile of the GRAd platform provides a robust foundation for a more efficient and streamlined regulatory pathway. By leveraging this prior knowledge, future GRAd-based vaccines can achieve accelerated clinical development while fully adhering to the ethical principles of replacement, reduction, and refinement of animal use in research.
MIT Department
Ragon Institute of MGH, MIT and Harvard
Harvard-MIT Program in Health Sciences and Technology
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.3390/vaccines14020157
