Relationship between natural and infection-induced antibodies in systemic autoimmune diseases (SAD): SLE, SSc and RA
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Authors: Borocz, K.; Simon, D.; Erdo-Bonyar, S.; Kovacs, K. T.; Tuba, E.; Czirjak, L.; Nemeth, P.; Berki, T.
Abstract
Infection or vaccine-induced T cell-dependent immune response and the subsequent high-affinity neutralizing antibody production have been extensively studied, while the connection between natural autoantibodies (nAAbs) and disease-specific antibodies has not been thoroughly investigated. Our goal was to find the relationship between immunoglobulin (Ig)M and IgG isotype nAAbs and infection or vaccine-induced and disease-related autoantibody levels in systemic autoimmune diseases (SAD). A previously described indirect enzyme-linked immunosorbent assay (ELISA) test was used for detection of IgM/IgG nAAbs against citrate synthase (anti-CS) and F4 fragment (anti-F4) of DNA topoisomerase I in 374 SAD samples, with a special focus on systemic lupus erythematosus (SLE) (n = 92), rheumatoid arthritis (n = 73) and systemic sclerosis (n = 157) disease groups. Anti-measles IgG and anti-dsDNA IgG/IgM autoantibodies were measured using commercial and in-house indirect ELISA tests. In all SAD groups the anti-measles IgG-seropositive cases showed significantly higher anti-CS IgG titers (P = 0 center dot 011). In anti-dsDNA IgG-positive SLE patients, we detected significantly higher levels of anti-CS and anti-F4 IgG nAAbs (P = 0 center dot 001 and < 0 center dot 001, respectively). Additionally, we found increased levels of IgM isotypes of anti-CS and anti-F4 nAAbs in anti-dsDNA IgM-positive SLE patients (P = 0 center dot 002 and 0 center dot 016, respectively). The association between IgG isotypes of pathogen- or autoimmune disease-related antibodies and the IgG nAAbs may underscore the immune response-inducible nature of the diseases investigated. The relationship between protective anti-dsDNA IgM and the IgM isotype of anti-F4 and anti-CS may provide immunoserological evidence for the beneficial roles of nAAbs in SLE patients.
Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults
NATURE
Authors: Mulligan, Mark J.; Lyke, Kirsten E.; Kitchin, Nicholas; Absalon, Judith; Gurtman, Alejandra; Lockhart, Stephen; Neuzil, Kathleen; Raabe, Vanessa; Bailey, Ruth; Swanson, Kena A.; Li, Ping; Koury, Kenneth; Kalina, Warren; Cooper, David; Fontes-Garfias, Camila; Shi, Pei-Yong; Tuereci, Oezlem; Tompkins, Kristin R.; Walsh, Edward E.; Frenck, Robert; Falsey, Ann R.; Dormitzer, Philip R.; Gruber, William C.; Sahin, Ugur; Jansen, Kathrin U.
Abstract
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(1), a pandemic. With rapidly accumulating numbers of cases and deaths reported globally(2), a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 mu g, 30 mu g or 100 mu g of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 mu g was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-mu g dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.