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SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

ABSTRACT: mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

SUBMITTER: Jaycox JR

PROVIDER: S-EPMC9996559 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

Jaycox Jillian R JR Lucas Carolina C Yildirim Inci I Dai Yile Y Wang Eric Y EY Monteiro Valter V Lord Sandra S Carlin Jeffrey J Kita Mariko M Buckner Jane H JH Ma Shuangge S Campbell Melissa M Ko Albert A Omer Saad S Lucas Carrie L CL Speake Cate C Iwasaki Akiko A Ring Aaron M AM

Nature communications 20230309 1

mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses a ...[more]

PMID: 36894554

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Project description:IntroductionPatients on peritoneal dialysis (PD) present an impaired humoral response against SARS-CoV-2, at least after the initial vaccination and booster dose. Until now, the effect of a fourth dose has not been established. The aim of the present study is to evaluate the long-term dynamics of the humoral response of PD patients to multiple doses of SARS-CoV-2 vaccines, focusing on the effect of the fourth dose.MethodsThis is an analysis of the prospective and multicentric SENCOVAC study. We included patients on PD without additional immunosuppression that had received at least 3 SARS-CoV-2 mRNA vaccine doses. We evaluated anti-spike antibody titers after the initial vaccination, third and fourth doses, using prespecified fixed assessments (i.e., baseline, 28 days, 3, 6, and 12 months after completing the initial vaccine schedule). Breakthrough infections were also collected.ResultsWe included 164 patients on PD (69% males, 62 ± 13 years old). In patients who had received only two doses, the rates of positive humoral response progressively decreased from 96% at 28 days to 80% at 6 months, as did with anti-spike antibody titers. At 6 months, 102 (62%) patients had received the third vaccine dose. Patients with the third dose had higher rates of positive humoral response (p = 0.01) and higher anti-spike antibody titers (p < 0.001) at 6 months than those with only 2 doses. At 12 months, the whole cohort had received 3 vaccine doses, and 44 (27%) patients had an additional fourth dose. The fourth dose was not associated to higher rates of positive humoral response (100 vs. 97%, p = 0.466) or to statistically significant differences in anti-spike antibody titers as compared to three doses (p = 0.371) at 12 months. Prior antibody titers were the only predictor for subsequent higher anti-spike antibody titer (B 0.53 [95%CI 0.27-0.78], p < 0.001). The 2 (1.2%) patients that developed COVID-19 during follow-up had mild disease.ConclusionsPD presents an acceptable humoral response with three doses of SARS-CoV-2 vaccines that improve the progressive loss of anti-spike antibody titers following two vaccine doses.

Project description:Background With the persisting low vaccination intake, particularly in children of low-and middle-income countries (LMICs), seroepidemiological studies are urgently needed to guide and tailor COVID-19 pandemic response efforts in schools and to put mitigation strategies in place for a future post-pandemic resurgence. However, there is limited data on SARS-CoV-2 infection-induced and vaccine-induced humoral immunity in schoolchildren in LMICs, including Ethiopia. Methods As the spike receptor binding domain (RBD) is the major target for neutralization antibodies and useful to predict the correlates of protection, we used an in-house anti-RBD IgG ELISA to assess and compare infection-induced antibody response at two-time points and BNT162b2 (BNT) vaccine-induced antibody response at a one-time point in schoolchildren in Hawassa, Ethiopia. In addition, we measured and compared the levels of binding IgA antibodies to spike RBD of SARS-CoV-2 Wild type, Delta, and Omicron variants in a small subset of unvaccinated and BNT-vaccinated schoolchildren. Results When we compare SARS-CoV-2 infection-induced seroprevalences among unvaccinated school children (7-19 years) at the two blood sampling points with a 5-month interval, we observed an over 10% increase, from 51.8% (219/419) in the first week of December 2021 (post-Delta wave) to 67.4% (60/89) by the end of May 2022 (post-Omicron wave). Additionally, we found a significant correlation (p = 0.001) between anti-RBD IgG seropositivity and a history of having COVID-19-like symptoms. Compared to the levels of SARS-CoV-2 infection-induced anti-RBD IgG antibodies before vaccination, higher levels of BNT vaccine-induced anti-RBD IgG antibodies were observed even in SARS-CoV-2 infection-naïve schoolchildren of all age groups (p = 0.0001). Importantly, one dose of the BNT vaccine was shown to be adequate to elicit a strong antibody response in schoolchildren with pre-existing anti-RBD IgG antibodies comparable to that of SARS-CoV-2 infection-naive schoolchildren receiving two doses of BNT vaccine, suggesting a single dose administration of the BNT vaccine could be considered for schoolchildren who had prior SARS-CoV-2 infection when a shortage of vaccine supply is a limiting factor to administer two doses irrespective of their serostatus. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Irrespective of schoolchildren’s vaccination status, we observed a similar pattern of significantly higher levels of IgA antibodies to Delta-RBD than to Omicron-RBD (p < 0.001) in a randomly selected subset of schoolchildren, yet comparable to Wuhan-RBD, suggesting these schoolchildren were more likely to have had SARS-CoV-2 infection with Delta variant. Additionally, we noted a broader IgA antibody reactivity to SARS-CoV-2 variants in vaccinated schoolchildren with prior SARS-CoV-2 infection, supporting the superiority of hybrid immunity. Conclusion Our serological data indicate a significant increase in SARS-CoV-2 seroprevalence in children at a post-Omicron five-month follow-up compared to a post-Delta enrolment. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Hybrid immunity would likely provide a broader humoral immunity against Wuhan strain, Delta, and Omicron variants than natural infection or vaccination alone does. However, future longitudinal cohort studies in SARS-CoV-2-naïve and COVID-19-recovered schoolchildren receiving the BNT vaccine are needed for a better understanding of the kinetics, breadth, and durability of BNT vaccine-induced multivariant-cross reactive immunity.

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SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

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SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

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