Microbes and Infection最新文献

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies usually rely on cross-sectional data of large cohorts but limited repeated samples, overlooking significant inter-individual antibody kinetic differences. By combining Luminex, activation-induced marker (AIM) and IFN-γ/IL-2 Fluorospot assays, we characterized the IgM, IgA, and IgG antibody kinetics using 610 samples from 31 healthy adults over two years after COVID-19 vaccination, and the T-cell responses six months post-booster. Antibody trajectories varied among isotypes: IgG decayed slowly, IgA exhibited an initial sharp decline, which gradually slowed down and stabilized above the seropositivity threshold. Contrarily, IgM rapidly dropped to undetectable levels after primary vaccination. Importantly, three vaccine doses induced higher and more durable anti-spike IgG and IgA levels compared to two doses, whereas infection led to the highest antibody peak and slowest antibody decay rate compared to vaccination. Comparing with ancestral virus, antibody levels recognizing Omicron subvariants had a faster antibody decay. Finally, polyfunctional T cells were positively associated with subsequent IgA responses. These results revealed distinctive antibody patterns by isotype and highlight the benefits of booster doses in enhancing and sustaining antibody responses.

Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood. We investigated the importance of C3 in L. interrogans serovar Kennewicki strain Pomona Fromm (LPF) infection. Lack of C3 leads to decreased leukocyte number, impaired inflammatory response and failure to eliminate bacteria during the early stages of infection, which may cause interstitial nephritis later. These findings could be explained, at least in part, by the lower presence of local opsonins. Furthermore, antibody production against Leptospira was compromised in the absence of C3, highlighting the importance of CR2 in B lymphocyte proliferation and the adjuvant role of C3d in humoral immunity. Leptospires can be eliminated through the urine, and according to our study, the lack of C3 delays the elimination of LPF through urine during the early stages of the infection. These results strongly suggest the crucial role of C3 protein in orchestrating an appropriate inflammatory response against LPF infection and in effectively eliminating the bacteria from the body during the acute phase of leptospirosis.

Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.

Streptococcus pneumoniae, a leading cause of corneal infections worldwide, are extremely aggressive despite antibiotic sensitivity and exhibit increased resistance towards antibiotics. Antimicrobial peptides are often considered as potent alternatives against antibiotic resistance and here we have investigated the possible roles of S100A12, a host defense peptide, in wound healing and S. pneumoniae infection. S100A12 significantly inhibited growth of S. pneumoniae by disruption of membrane integrity along with increased generation of reactive oxygen species. Additionally, S100A12 accelerated cell migration and wound closure in human corneal epithelial cells and in a murine corneal wound model by activation of EGFR and MAPK signaling pathways.

Human norovirus (HuNoV) is a major global cause of acute gastroenteritis, with vaccine development facing several challenges. Despite years of research, there are currently no licensed vaccines available for controlling HuNoVs. Here, we describe the construction and testing of a replication-deficient Sendai virus (SeV) vector as a potential vaccine candidate against the HuNoV GII.4 genotype. SeV was chosen as the vaccine backbone due to its non-pathogenic nature in humans, its capability for long-term antigen expression in mammalian cells, and its suitability for mucosal administration. By inserting the HuNoV GII.4 capsid gene, VP1, into the SeV genome, we generated a replication-deficient SeV (SeV/dP.VP1) vector. The resultant SeV/dP.VP1 virus were observed to successfully express the inserted NoV VP1 gene upon infection. Inoculating the vaccine into wild-type mice elicited NoV-specific IgG antibodies, along with INF-γ and IL-2-producing T cells, through both intranasal (i.n.) and intramuscular (i.m.) immunization. Furthermore, a significant level of NoV-specific IgA was detected in lung homogenates after i.n. immunization, particularly using a high dose of the viral vector. Additionally, a synergistic effect was observed with heterologous prime-boost regimens using SeV/dP.VP1 and MVA.VP1 vectors, indicating the potential for more robust immune responses when the vaccine design is optimized. Our study demonstrates the potential of a SeV vaccine candidate in eliciting a broad immune response and lays the foundation for further exploration of the SeV vector platform's potential as a HuNoV vaccine. Additionally, the results emphasize the importance of vaccine dosage and administration route, highlighting the need for tailored immunization strategies.