UNASSIGNED: It is important to figure out the immunity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reinfection to understand the response of humans to viruses. A serological survey for previously infected populations in Jiangsu Province was conducted to compare the antibody level of SARS-CoV-2 in reinfection by Omicron or not.
UNASSIGNED: Reinfection with SARS-CoV-2 was defined as an individual being infected again after 90 days of the initial infection. Telephone surveys and face-to-face interviews were implemented to collect information. Experimental and control serum samples were collected from age-sex-matched reinfected and non-reinfected cases, respectively. IgG anti-S and neutralizing antibodies (Nab) concentrations were detected by the Magnetism Particulate Immunochemistry Luminescence Method (MCLIA). Antibody titers were log(2)-transformed and analyzed by a two-tailed Mann-Whitney U test. Subgroup analysis was conducted to explore the relationship between the strain type of primary infection, SARS-Cov-2 vaccination status, and antibody levels. Multivariate linear regression models were used to identify associations between reinfection with IgG and Nab levels.
UNASSIGNED: Six hundred thirty-one individuals were enrolled in this study, including 327 reinfected cases and 304 non-reinfected cases. The reinfection group had higher IgG (5.65 AU/mL vs. 5.22 AU/mL) and Nab (8.02 AU/mL vs. 7.25 AU/mL) levels compared to the non-reinfection group (p < 0.001). Particularly, individuals who had received SARS-CoV-2 vaccination or were initially infected with the Wild type and Delta variant showed a significant increase in antibody levels after reinfection. After adjusting demographic variables, vaccination status and the type of primary infection together, IgG and Nab levels in the reinfected group increased by log(2)-transformed 0.71 and 0.64 units, respectively (p < 0.001). This revealed that reinfection is an important factor that affects IgG and Nab levels in the population.
UNASSIGNED: Reinfection with Omicron in individuals previously infected with SARS-CoV-2 enhances IgG and Nab immune responses.

In this study, sodium pentaborate pentahydrate (NaB) and Hypericum perforatum (HP) oil were incorporated into polyvinyl alcohol (PVA) and chitosan (CH) polymer blend to obtain membranes by solution casting method. In order to see the synergistic effects of NaB and HP oil on the biological and physical properties of the membranes NaB and HP oil were incorporated into membrane matrix in different ratios. Fourier-transform infrared spectroscopy (FTIR) results showed that no significant bond formation between the bioactive components and the PVA:CH matrix. According to mechanical test results, Young\'s Modulus and elongation at break decreased from 426 MPa to 346 MPa and 52.23 % to 15.11 % for neat PVA:CH membranes and NaB and HP oil incorporated PVA:CH (PVA:CH@35NaB:HP) membranes, respectively. Antimicrobial activity tests have shown the membranes were over 99 % effective against Escherichia coli, Staphylococcus aureus, and Candida albicans, underlining their potential for infection control. Cytocompatibility assay performed with Human Dermal Fibroblast (HDFa) cells highlight the biocompatibility of the membranes, revealing 74.84 % cell viability after 72 h. The properties of NaB and HP oil doped PVA:CH based membranes obtained from these experiments reveal the promise of a versatile membrane for applications in wound healing, tissue engineering and other biomedical fields.

UNASSIGNED: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition.
UNASSIGNED: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA).
UNASSIGNED: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

Intra-articular adeno-associated virus (AAV) gene therapy has been explored as a potential strategy for joint diseases. However, concerns of low transduction efficacy, off-target expression, and neutralizing antibodies (Nabs) still need to be addressed. In this study, we demonstrated that AAV6 was the best serotype to transduce joints after screening serotypes 1 to 9. To develop a more effective AAV vector, a set of novel AAV capsids were rationally engineered. The mutant AAV62 created by swapping variable region I (VRI) of AAV2 into AAV6 induced a higher transduction efficiency per AAV genome copy number. To further investigate the roles of specific amino acids in the transduction of AAV62 and AAV6, we found out that AAV6D with the deletion of threonine at residue 265 induced a 2-fold higher transduction than AAV6, while the transduction efficiency from AAV6M with the mutation of alanine to glutamine at residue 263 was 10-fold lower. AAV6D efficiently transduced both synoviocytes and chondrocytes with low AAV genome copy numbers in other tissues and less Nab formation. This study demonstrates that novel AAV mutants with rational engineering may enhance joint transduction after intra-articular administration in mice, with the potential to evade AAV Nabs and minimize off-target effects in the liver.

Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is a matricellular protein involved in several biological processes including cell adhesion, growth factor availability, extracellular matrix remodeling and immune-regulation. SPARC has also been associated with a variety of diseases including diabetes, colon cancer, and leukemia. The expression of SPARC in different diseases exhibits some degree of ambiguity, especially in hemopathies. Herein, we review the current expression and effects of SPARC in various hematologic disorders with respect to nanoparticle albumin bound innovative therapies and related diagnostic research, providing a clinical perspective on the use of NAB technology in the frontier treatment of hematologic diseases.

UNASSIGNED: COVID-19 pandemic causes severe acute respiratory syndrome and requires rapid action. The development of effective safe vaccines become a global priority for achieving herd immunity. Vaccination is expected to form specific antibodies against the SARS-CoV-2 spike protein which can neutralize the virus, preventing the virus from binding with ACE 2 receptors.
UNASSIGNED: Evaluating and to know if there any differences of kinetics antibody levels from recipient\'s anti-IgG S-RBD and NAb with complete second dose CoronaVac Vaccine, to determine the antibody response in preventing SARS-CoV-2.
UNASSIGNED: A prospective-cohort study using observational analytics was conducted from January-April 2021 at Dr. Soetomo Hospital, Surabaya. A total of 50 subjects are healthcare workers who received two doses of CoronaVac. The IgG S-RBD and NAb levels were measured on Maglumi 800 device (SNIBE, China). Differences in IgG S-RBD and NAb levels before vaccination and after second dose CoronaVac vaccination on 14th day, on 28th day, ware tested using Friedman and Wilcoxon tests.
UNASSIGNED: Mean values of IgG S-RBD and NAb have fluctuated. There was a significant difference between IgG S-RBD and NAb levels on day-0 (0.090 vs 18.630; p < 0.001) and day-28 (141.266 vs 116.640; p = 0.037). The median value showed the IgG S-RBD level on day-28 was much better than NAb value (141,266 v 116,640).
UNASSIGNED: CoronaVac will form persistent antibodies. Despite antibody development, the acquired humoral immunity decreased at 28 days after full CoronaVac immunization. Kinetics of antibody NAb decreased more rapidly than IgG S-RBD.

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against the coronavirus disease 2019 (COVID-19) pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of an antibody targeting a conserved and universal epitope is urgently needed. A subset of neutralizing antibodies (NAbs) against COVID-19 from convalescent patients were isolated in our previous study. In this study, we investigated the accommodation of these NAbs to SARS-CoV-2 variants of concern (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of the SARS-CoV-2 Omicron variant. In addition, we determined the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 spike (S) protein complexed with three monoclonal antibodies targeting different epitopes, including 553-49, 553-15, and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes the virus by disassembling S trimers. IgG 553-15, an antibody that neutralizes all of the VOCs except Omicron, cross-links two S trimers to form a trimer dimer, demonstrating that 553-15 neutralizes the virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 553-49 and other antibodies targeting this highly conserved epitope as promising therapeutic reagents for COVID-19. IMPORTANCE The emergence of the Omicron strain of SARS-CoV-2 caused higher immune escape, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. In this study, we identified a SARS-CoV-2 neutralizing antibody, 553-49, which neutralizes all variants by targeting a completely conserved novel epitope. In addition, we revealed that IgG 553-15 neutralizes SARS-CoV-2 by cross-linking virions and that 553-60 functions by blocking receptor binding. Comparison of different receptor binding domain (RBD) epitopes revealed that the 553-49 epitope is hidden in the S trimer and keeps a high degree of conservation during SARS-CoV-2 evolution, making 553-49 a promising therapeutic reagent against the emerging Omicron and future variants of SARS-CoV-2.

Neutrophil extracellular traps (NETs) are an important means by which the body fights against exogenous bacteria. However, studies have shown that excessive NETs release can damage other cells. Accumulating evidence has shown that butyric acid can alleviate the inflammatory response of cells. However, the effect of butyric acid on Staphylococcus aureus-induced NETs formation and its underlying mechanism are still unclear. In this study, western blotting, immunofluorescence and CCK-8 assays were used to examine the effect of NETs formation by sodium butyrate (NaB). The results showed that NaB suppressed the release of S. aureus-induced NETs formation, as indicated by decreases in the levels of DNA, histones, myeloperoxidase, and neutrophil elastase. S. aureus can induce autophagy, and autophagy plays a key role in the formation of NETs. Our data showed that NaB activated mammalian target of rapamycin (mTOR) and the kinases protein kinase B (AKT) and unc-51 like kinase 1 (ULK1) at Ser757 and inhibited AMP-activated protein kinase (AMPK). To explore whether NaB inhibited the formation of NETs by inhibiting autophagy, we added 3-methyladenine (autophagy inhibitor) (3-MA, 5 mM) to bovine neutrophils, and the results showed that 3-MA significantly inhibited NETs release. Furthermore, we found that NETs and their component histones exhibited significantly increased the cytotoxic effects on bovine mammary epithelial cells (BMECs), indicating that NETs and their component histones play a key role in BMEC damage. In conclusion, NaB can reduce the excessive formation of NETs by inhibiting autophagy, thus reducing the damaging effect of NETs on BMECs.