Shigellosis is a diarrheal disease and the World Health Organization prompts the development of a vaccine against Shigella flexneri. The autotransporters SigA, Pic and Sap are conserved among Shigella spp. We previously designed an in silico vaccine with immunodominat epitopes from those autotransporters, and the GroEL protein of S. typhi as an adjuvant. Here, we evaluated the immunogenicity and protective efficacy of the chimeric multiepitope protein, named rMESF, in mice against lethal infection with S. flexneri. rMESF was administered to mice alone through the intranasal (i.n.) route or accompanied with Complete Freund’s adjuvant (CFA) intradermically (i.d.), subcutaneously (s.c.), and intramuscular (i.m.), as well as with Imject alum (i.m.). All immunized mice increased IgG, IgG1, IgG2a, IgA and fecal IgA titers compared to PBS+CFA and PBS+alum control groups. Furthermore, i.n. immunization of mice with rMESF alone presented the highest titers of serum and fecal IgA. Cytokine levels (IFN-γ, TNF-α, IL-4, and IL-17) and lymphocyte proliferation increased in all experimental groups, with the highest lymphoproliferative response in i.n. mice immunized with rMESF alone, which presented 100% protection against S. flexneri. In summary, this vaccine vests protective immunity and highlights the importance of mucosal immunity activation for the elimination of S. flexneri.
Introduction
Gestational diabetes (GDM) is one of the most common complications in pregnancy, with a prevalence that continues to rise. At the time of the COVID-19 epidemic, immediate reorganisation and adjustment of the system was needed. Telemedicine support was offered in order to provide high-quality treatment to pregnant women. However, the success of the treatment is unknown. We therefore aimed to evaluate COVID-19 epidemic effects on pregnancy outcomes in GDM.
Methods
The maternal outcomes (insulin treatment, gestational weight gain, caesarean section, hypertensive disorders) and perinatal outcomes (rates of large and small for gestational age, preterm birth and a composite child outcome) of women visiting a university hospital diabetes clinic from March to December 2020 were compared with those treated in the same period in 2019.
Results
Women diagnosed with GDM during the COVID-19 epidemic (n=417), were diagnosed earlier (23.9 [11.7–26.0] vs. 25.1 [21.8–26.7] gestational week), had higher fasting glucose (5.2 [5.0–5.4] vs. 5.1 [4.8–5.3] mmol/l) and earlier pharmacological therapy initiation, and had achieved lower HbA1c by the end of followup (5.1% (32.2 mmol/mol) [4.9% (30.1 mmol/mol)–5.4% (35.0 mmol/mol)] vs. 5.2% (33.3 mmol/mol) [5.0% (31.1 mmol/mol) – 5.4%·(35.5 mmol/mol)], p<0.001) compared to a year before (n=430). No significant differences in perinatal outcomes were found.
Conclusions
Although GDM was diagnosed at an earlier gestational age and higher fasting glucose concentration was present at the time of diagnosis, the COVID-19 epidemic did not result in worse glucose control during pregnancy or worse pregnancy outcomes in Slovenia.
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