Some persons who have recovered from Covid-19 have antibodies to the spike protein of SARS-CoV-2. In 43 such persons who had received a first mRNA vaccine dose, high levels of neutralizing antispike ...antibodies were produced — in many cases even higher than after a second dose in 67 persons without baseline antibodies to the virus. Systemic reactions were more common in those seropositive before vaccination.
Objective
The underlying mechanisms and molecular factors influencing intervertebral disc (IVD) homeostasis and degeneration remain clinically relevant. Tenomodulin (Tnmd) and chondromodulin (Chm1) ...are antiangiogenic transmembrane glycoproteins, with cleavable C-terminus, expressed by IVD cells that are implicated in the onset of degenerative processes. We evaluate the organ-level biomechanical impact of knocking out Tnmd alone, and Tnmd and Chm1, simultaneously.
Design
Caudal (c5-8) and lumbar vertebrae (L1-4) of skeletally mature male and female 9-month-old wildtype (WT), Tnmd knockout (Tnmd−/−), and Tnmd/Chm1 double knockout (Tnmd−/−/Chm−/−) mice were used (n = 9-13 per group). Disc height index (DHI), histomorphological changes, and axial, torsional, creep, and failure biomechanical properties were evaluated. Differences were assessed by one-way ANOVA with post hoc Bonferroni-corrected comparisons (P < 0.05).
Results
Tnmd−/−/Chm1−/− IVDs displayed increased DHI and histomorphological scores that indicated increased IVD degeneration compared to the WT and Tnmd−/− groups. Double knockout IVDs required significantly less torque and energy to initiate torsional failure. Creep parameters were comparable between all groups, except for the slow time constant, which indicated faster outward fluid flow. Tnmd−/− IVDs lost fluid faster than the WT group, and this effect was amplified in the double knockout IVDs.
Conclusion
Knocking out Tnmd and Chm1 affects IVD fluid flow and organ-level biomechanical function and therefore may play a role in contributing to IVD degeneration. Larger effects of the Tnmd and Chm1 double knockout mice compared to the Tnmd single mutant suggest that Chm1 may play a compensatory role in the Tnmd single mutant IVDs.
In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in ...vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.
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•Antibody responses after SARS-CoV-2 mRNA vaccination target RBD, NTD, and S2•SARS-CoV-2 mRNA vaccination induces a high rate of non-neutralizing antibodies•Crossreactive antibodies to seasonal β-coronaviruses are induced by vaccination•Variant mutation N501Y enhances affinity to human ACE2 while E484K reduces it
An analysis of mRNA vaccine-induced polyclonal antibodies and plasmablast-derived monoclonal antibodies from individuals vaccinated against SARS-CoV-2 identifies a high proportion of non-neutralizing antibodies and the induction of cross-reactive antibodies to seasonal coronaviruses and also maps the regions in the spike protein that are targeted, even among viral variants.
Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of ...USA-WA1/2020 strain in mouse lungs results in "mouse-adapted" SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.
It is thought that mRNA-based vaccine-induced immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes quickly, based mostly on short-term studies. Here, we analyzed the ...kinetics and durability of the humoral responses to SARS-CoV-2 infection and vaccination using >8,000 longitudinal samples collected over a 3-year period in New York City. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state antibody titers than naive individuals. Antibody kinetics were characterized by two phases: an initial rapid decay, followed by a stabilization phase with very slow decay. Booster vaccination equalized the differences in antibody concentration between participants with and without hybrid immunity, but the peak antibody titers decreased with each successive antigen exposure. Breakthrough infections increased antibodies to similar titers as an additional vaccine dose in naive individuals. Our study provides strong evidence that SARS-CoV-2 antibody responses are long lasting, with initial waning followed by stabilization.
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•COVID-19-vaccine-induced immunity wanes but stabilizes at an individual setpoint•Pre-existing immunity results in rapid antibody responses upon vaccination•Boosters equalize antibody titers between individuals with and without hybrid immunity•Antibody kinetics show two phases: an initial rapid decay followed by a steady state
SARS-CoV-2 mRNA-based vaccine-induced immunity is thought to wane quickly based on short-term studies. Using longitudinal data, Srivastava et al. find that participants with hybrid immunity show faster, higher antibody responses after initial vaccination, but boosters evened out differences. Modeling of antibody kinetics revealed an initial rapid decay followed by a stabilization phase, challenging the idea that vaccine immunity fades quickly.
The PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) cohort follows health care workers with and without documented coronavirus disease 2019 (COVID-19) since April 2020. We report our ...findings regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-binding antibody stability and protection from infection in the pre-variant era. We analyzed data from 400 health care workers (150 seropositive and 250 seronegative at enrollment) for a median of 84 days. The SARS-CoV-2 spike-binding antibody titers were highly variable with antibody levels decreasing over the first 3 months, followed by a relative stabilization. We found that both more advanced age (>40 years) and female sex were associated with higher antibody levels (1.6-fold and 1.4-fold increases, respectively). Only six percent of the initially seropositive participants “seroreverted.” We documented a total of 11 new SARS-CoV-2 infections (10 naive participants and 1 previously infected participant without detectable antibodies; P < 0.01), indicating that spike antibodies limit the risk of reinfection. These observations, however, only apply to SARS-CoV-2 variants antigenically similar to the ancestral SARS-CoV-2 ones. In conclusion, SARS-CoV-2 antibody titers mounted upon infection are stable over several months and provide protection from infection with antigenically similar viruses. IMPORTANCE SARS-CoV-2 is the cause of one of the largest noninfluenza pandemics of this century. This exceptional public health crisis highlights the urgent need for better understanding of the correlates of protection from infection and severe COVID-19. We established the PARIS cohort to determine durability and effectiveness of SARS-CoV-2 immune responses. Here, we report on the kinetics of SARS-CoV-2 spike-binding antibody after SARS-CoV-2 infection as well as reinfection rates using data collected between April 2020 and August 2021. We found that antibody levels stabilized at individual steady state levels after an initial decrease with seroreversion being found in only 6% of the convalescent participants. SARS-CoV-2 infections only occurred in participants without detectable spike-binding antibodies, indicating significant protection from reinfection with antigenically similar viruses. Our data indicate the importance of spike-binding antibody titers in protection prior to vaccination and the wide circulation of antigenically diverse variants of concern.
Postoperative range of motion (ROM) is an important measure for the functional outcome and overall success after total knee arthroplasty (TKA). While robotic knee systems have been shown to reduce ...pain and improve early function, the return of postoperative ROM specifically has not been adequately studied. The purpose of this study was to compare postoperative ROM in robotic and conventional TKA. We hypothesized that robotic TKA leads to an improvement in postoperative ROM.
A retrospective cohort study of 674 primary TKAs by a single surgeon between January 2018 and February 2023 was completed. Patients that did not have both a two-week follow up and eight-week follow up were excluded. Revision/conversion TKAs were excluded. The population was divided into two cohorts based on technique utilized: robotic versus conventional. Preoperative extension/flexion data, postoperative extension/flexion data at two-week and eight-week follow ups, and manipulation under anesthesia data were collected. ROM was defined as flexion minus extension. Chi-square tests were used to examine for differences between categorical variables and t-tests for continuous variables.
A total of 307 robotic and 265 conventional knees were included. There were no differences in demographics, mean follow up, or preoperative ROM between groups. The robotic group had significantly more flexion (99.20° vs. 96.98°; p=0.034) and ROM (97.81° vs. 95.56°; p=0.047) at the two-week follow up. The loss in ROM at the two-week follow up from preoperative ROM was significantly less for the robotic group (-11.21° vs. -14.16°; p=0.031). There were no significant differences in extension at either follow up, in flexion at the eight-week follow up, or in ROM at the eight-week follow up.
Robotic TKA leads to an improvement in postoperative flexion and ROM when compared to preoperative ROM at two-week follow up. These findings could partially explain the quicker recovery associated with robotic TKA.
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