Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

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BACKGROUND Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2–specific immunity correlate with disease severity. METHODS In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4 + T cells dominated over CD8 + T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 + and CD8 + T cells in general. CONCLUSION Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.

In this study of players in the NFL, the majority of ACL tears involved a noncontact mechanism, with the lower extremity exhibiting a dynamic valgus moment at the knee. These findings suggest that ACL injury prevention programs may reduce the risk of noncontact ACL tears in American football players.

Introduction Extensor tendon irritation and attritional tendon ruptures are potentially serious complications after open reduction and internal fixation of distal radius fractures. These complications are well recognized after dorsal plating of distal radii; and these are now being reported after errant screw placement during volar fixedangle plating. Intraoperative detection of improper screw placement is critical, as corrective action can be taken before completion of the operative procedure. The purpose of this study was to define the extensor tendon compartments at risk secondary to dorsal screw penetration and to compare pronation and supination fluoroscopic images with standard lateral images in demonstrating dorsal screw prominence during volar locked plating.Methods Eight fresh-frozen human cadaveric upper extremities underwent fixation with a volar, fixed-angle distal radius locked plate (Wright Medical Technology, Arlington, TN). Three fluoroscopic views (lateral, supinated, and pronated) followed by dorsal wrist dissections were compared to determine accuracy in detecting dorsal screw prominence and extensor tendon compartment violation. Subsequently, screws measuring 2, 4, 6, 8, and 10(mm longer than the measured depths were sequentially inserted into each distal locking screw, with each image deemed either "in" (completely inside the bone) or "out" (prominent screw tip dorsally-would typically be exchanged for a shorter screw intraoperatively). Results The radial most distal locking screw (position 1) violated either the first (25%) or second (75%) extensor tendon compartments. The average screw prominence required for radiographic detection was: 6.5(mm for lateral views and 2(mm for supinated views. Pronated views did not identify prominent screws. Screws occupying plate position 2 consistently entered Lister's tubercle, with 5/8 exiting the apex and 3/8 exiting the radial base. The average screw prominences for radiographic detection were: 2.75(mm-lateral views and 3.0(mm-supinated views. Although the screws entered the second dorsal compartment, they did not encroach upon either of the tendons. Screws occupying plate position 3 violated the third extensor tendon compartment in 7/8 specimens with 1/8 exiting the Ulan base of Lister's tubercle. The average screw prominences for radiographic detection were: 3.5 (mm-lateral views and 2.5(mm-pronated views. Supinated views did not identify prominent hardware. Screws occupying plate position 4 all violated the IV dorsal extensor compartment-2/8 screws were noted to tent the posterior interosseous nerve. The average screw prominences required for radiographic detection were: 4.0(mm-lateral HAND (2007) Conclusions Volar fixed-angle plating has shown great promise in the advancement of distal radius fracture management. We have seen in our referral practices and in the literature an increase in the number of extensor tendon complications arising from unrecognized dorsally prominent screws, pegs, or tines. Standard PA and lateral radiographs cann...

VZV-specific CD4-T cells in patients with zoster bear typical features of anergy. This phenotype is reversible and may serve as adjunct tool for monitoring VZV reactivations in high-risk patients.

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Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.