BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)a biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-Gastroenterology 2021;-:1-14 CLINICAL ATspike antibody levels and functional activity, anti-TNFa levels and adverse events (AEs) were detected longitudinally. RE-SULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFa, 118 non-anti-TNFa), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas w7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFa treated compared with non-anti-TNFa treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFa treated compared with non-anti-TNFa treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFa drug levels and vaccine responses did not affect anti-spike levels. Infection rate (w2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFa, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

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Shigella is a leading cause of diarrhea among children globally and of diarrheal deaths among children under 5 years of age in low-and middle-income countries. To date, no licensed Shigella vaccine exists. We review evidence that serum IgG antibodies to Shigella LPS represent a good correlate of protection against shigellosis; this could support the process of development and evaluation of Shigella vaccine candidates.Case-control and cohort studies conducted among Israeli soldiers serving under field conditions showed significant serotype-specific inverse associations between pre-exposure serum IgG antibodies to Shigella LPS and shigellosis incidence. The same serum IgG fraction showed a dose-response relationship with the protective efficacy attained by vaccine candidates tested in phase III trials of young adults and children aged 1-4 years and in Controlled Human Infection Model studies and exhibited mechanistic protective capabilities. Identifying a threshold level of these antibodies associated with protection can promote the development of an efficacious vaccine for infants and young children.

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SignificanceTissues are made up of cells and an extracellular matrix (ECM), a cross-linked network of stiff biopolymers. Cells actively alter the ECM structure and mechanics by applying contractile forces, which allow them to sense other distant cells and regulate many tissue functions. We study theoretically the decay of cell-induced displacements in fibrous networks, while quantifying the changes in the elastic properties of the cell's local environment. We demonstrate that cell contraction induce an anisotropic elastic state, i.e., unequal principal elastic moduli, in the ECM which dictates the slow decay of displacements. These observations suggest a new mechanical mechanism through which cells can mechanically communicate over long distances, and may provide biomaterials design parameters to guide morphogenesis in tissue engineering. AbstractThe unique nonlinear mechanics of the fibrous extracellular matrix (ECM) facilitates long-range cell-cell mechanical communications that would be impossible on linear elastic substrates. Past research has described the contribution of two separated effects on the range of force transmission, including ECM elastic non-linearity and fiber alignment. However, the relation between these different effects is unclear, and how they combine to dictate force transmission range is still elusive. Here, we combine discrete fiber simulations with continuum modeling to study the decay of displacements induced by a contractile cell in fibrous networks. We demonstrate that fiber non-linearity and fiber reorientation both contribute to the Page 2 of 32 strain-induced anisotropy of the elastic moduli of the cell's local environment. This elastic anisotropy is a "lumped" parameter that governs the slow decay of the displacements, and it depends on the magnitude of applied strain, either an external tension or an internal contraction as a model of the cell. Furthermore, we show that accounting for artificially-prescribed elastic anisotropy dictates the displacement decay induced by a contracting cell. Our findings unify previous single effects into a mechanical theory that explains force transmission in fibrous networks. This work provides important insights into biological processes that involve the coordinated action of distant cells mediated by the ECM, such that occur in morphogenesis, wound healing, angiogenesis, and cancer metastasis. It may also provide design parameters for biomaterials to control force transmission between cells, as a way to guide morphogenesis in tissue engineering.In addition, we find in Fig. 3C that the data points of 2 / 1 for all types of fibers can be approximately fitted by a master curve if plotted versus the normalized strain, / crit . Here crit is the critical strain, a characteristic parameter of the network, in which 2 / 1 becomes smaller than 0.9, and the strain-induced elastic anisotropy is significant. The normalized strain, / crit , similar to the normalized cell contraction, / crit in cell contraction networks, is another "emergent" dimensionless p...