Biology subjects

Battella, S.

Publications and source records attributed to Battella, S..

3 recordsLinked to original sources

bioRxiv2025

Non-clinical safety of GRAd vector-based COVID-19 and HIV vaccines supports a platform regulatory approach

The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. Here we present the complete non-clinical studies for two investigational vaccines based on the GRAd platform, a gorilla-derived group C adenoviral vector. When administered intramuscularly, GRAd-COV2 and GRAdHIVNE1 were well tolerated. Studies in rats and rabbits showed localized distribution and transient, non-adverse inflammatory responses, while successfully inducing expected immune responses to their respective antigens. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. 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.

pharmacology and toxicology↗

bioRxiv2022

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature.

Although the prime/boost interval can impact vaccine responses, the criteria for deciding its time length are poorly defined. To address this, we examined CD8 T cell responsiveness to boost in a BALB/c mouse model of intramuscular (i.m.) vaccination by priming with HIV-1 gag-encoding Chimpanzee adenovector, and boosting with HIV-1 gag-encoding Modified Vaccinia virus Ankara. We found that boost was more effective at day(d)100 than at d30 post-prime, as evaluated at d45 post-boost by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-expression (as a guide to memory status) and in vivo killing. RNA-sequencing of splenic gag-primed CD8 T cells at d100 revealed a quiescent, but highly responsive signature, that trended toward a central memory (CD62L+) phenotype. Interestingly, gag-specific CD8 T cell frequency selectively diminished in the blood at d100, relative to the spleen, lymph nodes and bone marrow. These results move forward the rational design of prime/boost intervals.

immunology↗

bioRxiv2020

Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19

The COVID-19 pandemic caused by the emergent SARS-CoV-2 coronavirus threatens global public health and there is an urgent need to develop safe and effective vaccines. Here we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV2. We show that our vaccine candidate, GRAd- COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies which neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, Th1- dominated cellular response in the periphery and in the lung. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV2 neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of GRAd-COV2 vaccine in a currently ongoing Phase I clinical trial (NCT04528641).

immunology↗