2372. Preliminary evidence of durable immune responses induced by self-amplifying mRNA (samRNA) vaccine candidates against SARS-CoV-2 in vaccine-naive South African population

BACKGROUND: CORAL-CEPI (NCT05435027) is the first test of samRNA-based SARS-CoV-2 vaccines in the African population, under-represented in SARS-CoV-2 vaccine studies. Antibody transience is an issue with first generation SARS-CoV-2 vaccines. This is a preliminary safety and immunogenicity report, showing durable IgG and neutralizing antibody (nAb) responses induced by samRNA vaccine candidates in a South African population. [Figure: see text] METHODS: This is an ongoing Phase I, open-label, dose-escalation study of samRNA candidates (R914, R912) encoding full-length Spike (S, Beta) and sequences of Nucleocapsid or selected non-S T cell epitopes (TCEs) (Fig.1). R914 (Part A; 3, 10 and 30 mcg) and R912 (Part B; 3 and 10 mcg) were administered as 1 or 2 doses in adults (18-65 years) in two cohorts (Fig.2): SARS-CoV-2 anti-N IgG seronegative or seropositive at baseline. Primary objective is safety and secondary objectives assess (at Vismederi srl) S-specific binding IgG (bAb) and nAbs against Beta and Delta variants of concern (VoC) as well as T cell responses against S and additional TCEs. [Figure: see text] RESULTS: Most reactogenicities were grade 1 or 2 and transient in nature (Fig.3). Ten out of 180 participants reported grade 3 solicited adverse events which resolved within 1-4 days. 99% of participants showed bAbs > 500 ELU/mL at 6 months, while 79% and 70% participants had nAbs > 500 ND(50) against Beta (included in vaccine), and Delta (cross-reactive), at 6 months in Part A, respectively. Antibody responses were durable up to at least 6 months after R914 and up to at least D57 after R912. The majority of subjects who received GRT-R914 had T cell responses to Non-Structural Protein (NSP) and Nucleocapsid antigens. T cell data from subjects vaccinated with GRT-R912 is pending. Fig.3 [Figure: see text] CONCLUSION: All doses of R914 and R912 were well-tolerated. Both vaccine candidates increased IgG titers against WT as well as nAb titers against selected VoCs. Antibody levels were durable up to at least 6 months after R914 and 57 days after R912 at all dose levels. Humoral immunity against additional VoCs and additional T cell data will be presented. These results showing similar nAb durability are observed with another samRNA vaccine assessed as boost following primary series with ChAdOx1 or mRNA (NCT05148962). DISCLOSURES: A. Koen, MD, Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit, South Africa – Johannesburg (South Africa): Employee E. Mitha, MBChB, Newtown Clinical Research Centre, South Africa - Newtown (South Africa): Employee J. Allagappen, MD, Setshaba Research Centre - Pretoria (South Africa): Employee A. Nagare, MBBS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds M. Dhar, MBBS, Shandukani Research - Johannesburg (South Africa): Employee M. Marrali, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Christine Palmer, 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 JC Kuan, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds L. Kraemer, PhD, Gritstone: Employee|Gritstone: Stocks/Bonds L. Arcebuche, PhD, Gritstone bio: Employee|Gritstone bio: Stocks/Bonds L. Hernandez, PhD, Gritstone bio: Employee|Gritstone bio: Stocks/Bonds Meghan Hart, ALM, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Sonia Kounlavouth, BS, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds Pedro Garbes, MD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Stocks/Bonds|Gritstone bio, Inc.: Stocks/Bonds A. Allen, MBBS, PhD, Gritstone bio, Inc.: Employee|Gritstone bio, Inc.: Ownership Interest|Gritstone bio, Inc.: Stocks/Bonds Karin Jooss, PhD, Gritstone bio: employee|Gritstone bio: Stocks/Bonds Shabhir A. Mahdi, PhD, Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit, South Africa – Johannesburg (South Africa): Employee