Values 1

Values 1.0?U/mL were interpreted as positive for anti\N SARS\CoV\2 antibodies and indicative of prior infection. respective DMT classes versus no DMT (reference). ACN3-9-1643-s001.docx (204K) GUID:?D537D660-0E01-4A49-9E1F-722B64592196 Abstract Objective To compare hybrid immunity (prior COVID\19 infection plus vaccination) and post\vaccination immunity to SARS CoV\2 in MS patients on different disease\modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post\vaccination immune responses. Methods Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18C60, who completed primary COVID\19 vaccination series 6?weeks previously were evaluated for SARS CoV\2\specific antibody responses with electro\chemiluminescence and multiepitope bead\based immunoassays and, in a subset, live virus immunofluorescence\based microneutralization assay. SARS CoV\2\specific cellular responses were assessed with cellular stimulation TruCulture IFN and IL\2 assay and, in a subset, with IFN and IL\2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID\19 infection while controlling for age, sex, DMT at vaccination, time\to\vaccine, and vaccine product. Results Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6?years; 76% female; 53% non\White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine\1\phosphate receptor modulators 13%; and no DMT 8%). Vaccine\to\collection time was 18.7 (7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory\confirmed prior COVID\19 infection had significantly increased antibody and cellular post\vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of Butoconazole antibody and cellular responses, while Butoconazole race/ethnicity was not. Interpretation Prior COVID\19 infection is associated with enhanced antibody and cellular post\vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups. Introduction Some of the disease\modifying therapies (DMTs) for MS suppress the immune system, which results in reduced immune responses to vaccinations. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 In a meta\analysis of COVID\19 vaccine studies in MS, post\vaccine seroconversion rates were 13\fold lower Butoconazole among patients on B\cell depleting anti\CD20 therapies (aCD20) and eightfold lower with S1P receptor modulators (S1P) as compared to patients not on a DMT. 24 Post\vaccine T\cell activation post\vaccine is suppressed with S1P 18 , 21 , 22 , 25 but largely intact with B\cell depleting therapies even in the absence of antibody responses. 4 , 6 , 8 , 10 , 16 , 17 , 18 , 21 , 22 , 25 , 26 , 27 An important unanswered question is whether post\vaccination immune responses are enhanced in MS patients who previously experienced SARS CoV\2 infection compared to PRKDC those without prior infection. The clinical relevance of hybrid immunityinfection plus vaccinationis increasing with the rising prevalence of SARS CoV\2 infection. As of November 2021 (pre\Omicron variant), 40% of the world population has already been infected with SARS CoV\2 at least once, 28 and in some areas, the prevalence was even higher, for example, 68% in South Africa. 29 Since the advent of the Omicron variant, half of the U.S. population was infected within months of this variant’s emergence. 30 Thus, hybrid immunity is the dominant mode of immunity in most countries and, by extension, among the MS patients in these countries. Several large, population\based studies have demonstrated that hybrid immunity affords a higher level of protection against reinfection and hospitalization than infection or vaccination alone. 31 , 32 , 33 , 34 , 35 The main mechanism underlying enhanced immunity is the strength and breadth of the antibody responses after vaccination of previously SARS\CoV\2Cinfected persons with secondary contributions from Spike\ and non\Spike\specific T\cell memory. 36 For example, persons with prior infection (PI) exhibit elevated induction of IFN\producing Spike\reactive CD4+ T cells following vaccination compared to those with no prior infection (NPI) 37 and expansion of spike\specific memory CD8+ T cells. 38 There is preliminary evidence that immunologic benefits of hybrid immunity may extend to patients with immune suppression, such as kidney and other solid organ transplant recipients. These patients have very attenuated humoral responses to vaccines but still exhibit a more robust post\vaccination Butoconazole antibody response if they had PI. Butoconazole 39 , 40 How antibody and cellular responses to COVID\19.