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

• Published in: Open forum infectious diseases 2023-11, Vol.10 (Supplement_2)
• Main 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
• Format: Article
• Language: English
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofad500.1993

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 > 500 ELU/mL at 6 months, while 79% and 70% participants had nAbs > 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