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
Authors: Koen A , Mitha E , Allagappen J , Nagare A , Dhar M , Marrali M , Palmer Christine , Venkatraman Harshni , Jaroslavsky Jason , Kuan J C , Kraemer L , Arcebuche L , Hernandez L , Hart Meghan , Kounlavouth Sonia , Garbes Pedro , Allen A , Jooss Karin , Mahdi Shabhir A 
Published: November 2023

Abstract

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.Fig. 1GRT-R914 encoding full-length Beta spike and partial sequences of Nucleocapsid, ORF3a, Membrane, and Non-structural Proteins (NSP) genes to provide T cell epitopes (TCE) outside of Spike GRT-R912 encoding full-length Beta spike and full sequences of Nucleocapsid, ORF3a, Membrane, and Non-structural Proteins (NSP) genes to provide TCE outside of Spike

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.

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 &gt; 500 ELU/mL at 6 months, while 79% and 70% participants had nAbs &gt; 500 ND50 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

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