Ab0092 Covid-19 Mrna Vaccines Based on the Ancestral Wuhan Strain Generate Anti-Sarscov2 Antibodies With Low Viral Inhibition Levels to Omicron Variants in People With Immune Mediated Inflammatory Diseases

Background: It is recommended that people with immune mediated inflammatory diseases (IMIDs) who take immunosuppressive medication receive at least 3 COVID-19 vaccinations in order to generate anti-SARSCoV2 antibody levels similar to those in general population. There is limited data for IMIDs regarding whether anti-SARSCoV2 antibodies developed following the original COVID-19 vaccines can inhibitory newer SARSCoV2 variants. Objectives: In people with IMIDs who received COVID-19 vaccines, to determine the ability of post vaccination antibodies to neutralize SARSCo-V2 variants. Methods: These data include individuals from a single centre participating in the Safety and immunogenicity of COVID-19 vaCcines in systemic immune mediated inflammatory Diseases (SUCCEED) project. Participants with inflammatory arthritis (IA n=36), systemic autoimmune rheumatic disease (SARDs N=28), or inflammatory bowel disease (IBD N=15) provided sera 1 and 3 months post COVID-19 vaccination. Samples with detectable post- vaccination anti-Spike and/or anti-receptor binding domain (RBD) antibodies 1 and 3 months post 3rd vaccination (1MV3, 3MV3) and 1 month post 4th vaccination (1MV4) with BNT162b2 or mRNA273 vaccines were tested for virus inhibition and compared to sera obtained from 59 COVID-19 vaccinated age-sex matched healthy controls < 90 days (PD3-1) or > 90 days (PD3-2) post 3rd and 4th vaccine (PD4-1). The Mesoscale Discovery V-PLEX SARS-CoV-2 Key Variant RBD Panel 1 (ACE2) kit was used to measure antibody viral inhibition capacity for the following SARSCoV2 variants: Wild type, Alpha B1.1.7, Beta B1.351, Delta B.1717.2, Omicron BA.1, Omicron BA, Omicron BA2.12, Omicron 2.75 and OMICRON BA.4/5. Pre-COVID-19 sera and pre-vaccine plasma samples were used to establish the lower limit of detection for virus inhibition (approximately 40% inhibition but variant-dependent). We report proportion of individuals having antibodies with any detectable inhibition and median (IQR) percent inhibition for each SARSCoV2 variant. Results: All participants received the original formulations of mRNA vaccines based on the ancestral Wuhan strain of SARSCoV2. We tested 263 samples from IMIDs (1 MV3 n=59, 3MV3 n=51, 1MV4 n=38) and controls (PD3-1 n=51, PD3-2 n=32, PD4-1 n=22). Fewer IMID participants than controls developed neutralizing antibodies to non-OMICRON variants (proportion with greater than threshold percent inhibition IMID vs Control: Wuhan wild type 87% vs 97% p=0.006; AlphaB1.1 87% vs 96% p=0.1; Beta B1.3 7%3 vs 87% p=0.1; Delta B1.7 85% vs 97% p=0.002). The proportion of individuals with neutralizing antibodies to OMICRON variants was low for both IMIDs and Controls (proportion with greater than threshold percent inhibition IMID vs Control for any OMICRON variant 59% vs 64%, OMICRON BA1 25% vs 26%, BA2 36% vs 45%, BA2.12 53% vs 61%, BA2.7 19% vs 22%, BA4.5 53% vs 62% all p=NS). The level of percent inhibition was generally highest after the 4th vaccine for most variants in both IMIDs and Controls (Figure 1). Across all time points IMIDs and controls had similar levels of anti-SARSCo-V2 antibody percent inhibition to each variant tested. Inhibition levels were lowest for the OMICRON variants. Conclusion: COVID-19 vaccination using original versions of mRNA vaccines leads to high levels of inhibiting antibodies to early COVID-19 variants but lower levels against OMICRON variants. While lower neutralizing levels do not imply less immune response to infection, these data support recommendations for revaccination with newer COVID-19 vaccines for people with IMIDs and for the general public. REFERENCES: NIL. Acknowledgements: Funding from the Public Health Agency of Canada and Research Manitoba. Disclosure of Interests: Carol A Hitchon advisory board Astra-Zeneca- unrelated product, Pfizer Canada- unrelated work, Jessica Ahmed: None declared, Paige Adams: None declared, Sandra Kiazyk: None declared, Charles N Bernstein Abbvie Canada, Janssen Canada, Pfizer Canada and Takeda Canada, Advisory board for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, JAMP Phamaceutical, Janssen Canada, Organon Canada, Pendopharm Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada (unrelated to work), Educational grants from AbbVie Canada, Bristol Myers Squibb Canada, Ferring Canada, Organon Canada, Pfizer Canada, Takeda Canada, Janssen Canada Research grants from AbbVie Canada, Amgen Canada, Janssen Pharmaceuticals, Pfizer, Sandoz Canada Takeda Canada, RuthAnn Marrie: None declared, John Kim: None declared, Sasha Bernatsky: None declared, Catherine Card: None declared.