Self-amplifying mRNA COVID-19 vaccine 'immunogenicity enhancer’ enters Phase 1 trial

The vaccine candidate, GRT-R910, delivers antigens from both the spike protein and non-spike proteins in the hope of offering broad protection across variants.

The new Manchester, UK trial will see the booster used in 20 volunteers aged 60+ who were initially vaccinated with AstraZeneca’s Vaxzevria (AZD1222): evaluating the ability of GRT-R910 to boost and expand the immunogenicity of first-generation vaccines.

The hypothesis is that a difference vaccine might complement the primary immune response from pre-existing vaccination in such a way that it would provide more benefit than an additional dose of the same vaccine.

Searching for longer-lasting immunity

GRT-R910 is part of Gritstone’s CORAL program, a second-generation COVID-19 vaccine platform that uses a self-amplified mRNA vector formulated with lipid nanoparticles to deliver a broad set of antigens against SARS-CoV-2 that includes both stabilized spike protein and highly conserved viral protein regions containing T cell epitopes.

Thanks to the self-amplifying mRNA, extended duration and magnitude of antigen production with such vaccines may offer the opportunity of lowering vaccine doses or eliminate the need for repeat administrations, and has potential to safely elicit strong, durable and broad immune responses across SARS-CoV-2 variants, according to Gritstone.

The new UK study, in collaboration with The University of Manchester and Manchester University NHS Foundation Trust, will assess GRT-R910’s ability to boost and expand the immunogenicity of first-generation COVID-19 vaccines.

“Our self-amplifying mRNA COVID vaccine is designed to drive robust CD8+ T cell responses, in addition to strong neutralizing antibody responses, offering the promise of longer lasting immunity, especially in more vulnerable populations,”​ said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone.

“Additionally, since viral surface proteins like the spike protein are evolving and sometimes partially evading vaccine-induced immunity, we designed GRT-R910 to have broad therapeutic potential against a wide array of SARS-CoV-2 variants by also delivering highly conserved viral proteins that may be less prone to antigenic drift.”​

This open-label dose-escalation design study will examine dose, safety, tolerability, and immunogenicity of GRT-R910 at two dose levels at least 4 months after the second administration of their initial vaccine. Data from the trial is expected in the first quarter of 2022. 

The program is assessing candidates under four different trials: including a trial sponsored by the US National Institutes of Health which is assessing the vaccine in both previously unvaccinated individuals and as a booster after vaccines authorized in the US (mRNA or adenoviral-vectored vaccines) across wider age ranges.