2346. Preliminary results of durable immune response induced by a self-amplifying mRNA (samRNA) SARS-CoV-2 vaccine candidate, GRT-R910, in adults previously vaccinated with mRNA or AZD1222 primary series
Authors: Uriel Alison , Garbes Pedro , Nagare A , Kuan J C , Palmer Christine , Bae K , Jooss Karin , Rappaport A , Kachura Melissa , Kraemer L , Venkatraman Harshni , Jaroslavsky Jason , Kounlavouth Sonia , Marrali M , Hart Meghan , Betular J , Allen A , Green C , Osanlou O , Palfreeman Adrian , Turgut Tolga , Ustianowski Andrew 
Published: November 2023

Abstract

Background
Neutralizing antibodies (nAbs) induced by authorized SARS-CoV-2 vaccines wane within months, requiring frequent boosters. Preliminary safety and immunogenicity of a samRNA-based SARS-CoV-2 vaccine candidate (GRT-R910) administered as a booster following AZD1222 primary series in older (≥ 60 years) adults (Cohorts 1 & 2, CORAL-BOOST study, NCT05148962) were previously reported. Updated results of GRT-R910 administered as a 2-dose booster in older (≥ 60 years) adults who received a primary series of either AZD1222 or mRNA vaccines (Cohorts 3 (C3) & 4 (C4)) are now reported.

Methods
GRT-R910 encodes Wuhan Spike (S) and highly conserved non-S T cell epitopes, is being tested in this open-label phase I study, conducted in the UK. Two booster doses of 10µg GRT-R910 are assessed in older adults who have received (C3) or mRNA vaccines (C4) as primary series. Nine participants (C3) received an mRNA booster prior to enrollment. The primary objective is safety and secondary objectives include assessment of titers and durability of S-specific IgG (bAbs) and nAb responses of GRT-R910 boost vaccinations as well as T cell responses to S and non-S epitopes.

Results
Ten participants were enrolled in each cohort (C3 and C4). The majority of reactogenicity events were mild or moderate and transient in nature. Three subjects reported grade 3 solicited adverse events which resolved within 1-4 days. Local and systemic reactogenicities were milder with the 2nd booster compared to the 1st booster across all cohorts. All participants showed bAbs IgG &gt; 500 ELU/mL and nAbs against to the vaccine-specific strain and nAbs &gt; 500 ND50 at 6 months following GRT-R910 vaccination, regardless of age, primary vaccination series, or additional prior mRNA booster. T cell responses to S were boosted and maintained up to at least Day 57; analyses of non-S T cell responses are ongoing.

Conclusion
GRT-R910 was well tolerated as a booster in older adults regardless of primary SARS-CoV-2 vaccination series. The 2nd booster was less reactogenic than the 1st and less reactogenicity was observed in the older population. High and sustainable antibody responses were observed for at least 6 months against Wuhan Spike across different age groups. Data on other variants will also be presented.

Disclosures
Alison Uriel, MBBS, North Manchester General Hospital, UK. - Manchester (United Kingdom): Employee Pedro Garbes, MD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds|Gritstone bio, Inc.: Stocks/Bonds A. Nagare, MBBS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds JC Kuan, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Christine Palmer, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds K. Bae, PhD, Gritstone bio: Stocks/Bonds Karin Jooss, PhD, Gritstone bio: employee|Gritstone bio: Stocks/Bonds A. Rappaport, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Melissa Kachura, BS, Dynavax Technologies: WO2019040491A1|Dynavax Technologies: Stocks/Bonds|Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds L. Kraemer, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Harshni Venkatraman, MS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Jason Jaroslavsky, MS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Sonia Kounlavouth, BS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds M. Marrali, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Meghan Hart, ALM, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds J. Betular, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds A. Allen, MBBS, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Ownership Interest|Gritstone bio, Inc.: Stocks/Bonds C. Green, MBBS, University Hospitals Birmingham NHS Foundation Trust - Birmingham (United Kingdom): Employee O. Osanlou, MBBS, North Wales Clinical Research Facility - North Wales (United Kingdom) and Bangor University – North Wales (United Kingdom): Employee Adrian Palfreeman, MBBS, University Hospital of Leicester NHS Trust. - Leicester (United Kingdom): Employee Tolga Turgut, MBBS, North Manchester General Hospital, UK. - Manchester (United Kingdom): Employee Andrew Ustianowski, MD, PhD, Gilead: Honoraria|Gilead: Advisory Board|GSK: Honoraria|Janssen: Honoraria|Merck: Honoraria|Merck: Advisory Board|Sanofi: Honoraria|ViiV Healthcare/GSK: Advisory Board