0773: Additional Dose of SARS-CoV-2 Vaccine Improves Cross-Variant Neutralization Titers in Immunosuppressed Patients with Chronic Inflammatory Disease

Michael Paley¹, Parakkal Deepak², Wooseob Kim³, Monica Yang⁴, Vinay Chandrasekaran³, Guadalupe Oliva Escudero³, Katherine Huang³, Zhuoming Liu³, Lily McMorrow⁵, Mahima Thapa³, Matthew Ciorba³, Mehrdad Matloubian⁶, Lianne Gensler⁷, Mary Nakamura⁸, Sean Whelan³, William Buchser³, Ali Ellebedy³ and Alfred Kim⁵, ¹Washington University in St. Louis, Saint Louis, MO, ²Washington University in St. Louis, Saint Louis, ³Washington University in St. Louis, St. Louis, MO, ⁴UCSF, SF, CA, ⁵Washington University School of Medicine, St. Louis, MO, ⁶UCSF, San Francisco, CA, ⁷Department of Medicine, Division of Rheumatology, University of California San Francisco, San Francisco, CA, ⁸UCSF/SFVAHCS, San Francisco, CA

Background/Purpose: Most immunosuppressed patients with chronic inflammatory diseases (CID) mount total anti-Spike (S) IgG responses following vaccination with mRNA-based SARS-CoV-2 vaccines. Less is known, however, about cross-variant neutralization potential, an immune correlate of protection that highly associates with efficacy of vaccination. Here, we describe how an additional dose of SARS-CoV-2 mRNA vaccination influences both total anti-S IgG and neutralizing titers to variants of concern.

Methods: The COVID-19 Vaccine Responses in Patients with Autoimmune Disease (COVaRiPAD) study is a prospective assessment of mRNA-based vaccine immunogenicity and reactogenicity in patients with CID. A total of 340 adults with CIDs were enrolled, with 81 participants having samples available at both 5 months after completion of the initial series and 4 weeks after the third dose. Serum anti-SARS-CoV-2 spike (S) IgG⁺ binding and neutralizing antibody titers to vesicular stomatitis virus pseudotyped with S protein from D614G (common), (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.519 subvariant (Omicron) were quantified.

Results: When examining the effect of a third dose of vaccine, total anti-S IgG titers increased >100-fold for most classes with exception of those on B cell depleting therapies. The additional dose did increase neutralization titers to all variants tested in most immunosuppressive classes with n ≥ 4 (Table 2), including 3- to 9-fold increases in neutralization against Omicron.

Conclusion: Reassuringly, immunosuppressed patients with CID mounted improved total anti-S IgG and neutralizing antibody titers to variants of concern broadly across various immunosuppressive classes. This highlights the necessity to provide additional doses beyond the initial series, which likely will extend to doses beyond the third dose.
Table 1. Exponential fold change of total anti-S IgG titers between pre- and post-3rd dose of SARS-CoV-2 mRNA vaccination

Table 2. Exponential fold change of neutralizing titers to variants of concern (VOC) between pre- and post-3rd dose of SARS-CoV-2 mRNA vaccination
Disclosures: M. Paley, AbbVie/Abbott, Priovant Therapeutics, Inc., Lilly, JK Market Research; P. Deepak, None; W. Kim, None; M. Yang, None; V. Chandrasekaran, None; G. Oliva Escudero, None; K. Huang, None; Z. Liu, None; L. McMorrow, None; M. Thapa, None; M. Ciorba, AbbVie/Abbott, Pfizer, Bristol-Myers Squibb(BMS), Theravance, Incyte, Janssen; M. Matloubian, None; L. Gensler, Novartis, Pfizer Inc, UCB Pharma, AbbVie, Eli Lilly, Janssen, Gilead, Moonlake; M. Nakamura, Moderna; S. Whelan, Vir Biotechnology, AbbVie/Abbott, SAb Therapeutics; W. Buchser, None; A. Ellebedy, AbbVie/Abbott, Emergent BioSolutions; A. Kim, GlaxoSmithKline, Kypha Inc., Foghorn Therapeutics, Aurinia Pharmaceuticals, Exagen Diagnostics, Alexion Pharmaceuticals, Pfizer, AstraZeneca.