Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally ...profile innate and adaptive immune responses in 102 adults after the first, second, and third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, we identify key differences in the immune responses induced by ChAdOx1-S and BNT162b2 that correlate with antigen-specific antibody and T cell responses or vaccine reactogenicity. Unexpectedly, we observe that vaccination with ChAdOx1-S, but not BNT162b2, induces an adenoviral vector-specific memory response after the first dose, which correlates with the expression of proteins with roles in thrombosis with potential implications for thrombosis with thrombocytopenia syndrome (TTS), a rare but serious adverse event linked to adenovirus-vectored vaccines. The COVID-19 Vaccine Immune Responses Study thus represents a major resource that can be used to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.
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•Multi-omics profiling of responses in 102 adults after COVID-19 vaccination•Baseline and innate responses correlate with vaccine immunogenicity/reactogenicity•ChAdOx1-S, but not BNT162b2, induces an adenoviral memory response after the first dose•ChAdOx1-S memory response correlates with expression of pro-thrombotic proteins
Ryan et al. use a multi-omics approach to longitudinally profile innate and adaptive immune responses in blood collected from 102 adults at baseline and post-vaccination with the ChAdOx1-S, BNT162b2, or mRNA-1273 vaccines. The study reveals key differences in immune responses to adenovirus-vectored compared with mRNA COVID-19 vaccines.
To compare the effects of (three-dimensional) 3D vs. two-dimensional (2D) radiation therapy (RT) for carcinoma of the prostate on the prevalence and pathophysiology of anorectal dysfunction.
...Anorectal symptoms, motility, sensory function, and anal sphincter morphology were evaluated before and up to 2 years after randomly assigned hypofractionated vs. conventionally fractionated RT in 67 patients (median age, 69 years; range, 54-82 years) with localized prostate carcinoma, using either a 3D (n = 29) or 2D (n = 38) treatment technique.
Anorectal symptoms increased 4 to 6 weeks after RT and persisted in both patient groups. At 2 years, abnormalities included increased stool frequency (55% vs. 53%, p = NS), urgency of defecation (72% vs. 47%, p < 0.05), fecal incontinence (28% vs. 26%, p = NS), and rectal bleeding (38% and 42%, p = NS). Anorectal motility and sensory function deteriorated after RT in both groups with reductions in basal anal pressures, anal pressures in response to squeeze, rectal compliance, and rectal volumes associated with the desire to defecate. External but not internal sphincter thickness changed in the treatment groups although in different directions. However no differences in motility or sensory function were detected between the groups. Baseline anorectal motility but not treatment technique and the hypofracionated schedule were of independent prognostic significance for anorectal motor dysfunction and rectal bleeding respectively at 2 years.
The prevalence and pathophysiology of anorectal dysfunction 2 years after RT for prostate carcinoma was largely independent of the treatment techniques used in this study.
To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate.
Thirty-eight patients, median age 71 (range, ...50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT.
Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency.
Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.
