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Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.β, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.

Objectives: The aim of this study was to generate new evidence on how The Daily Mile (TDM), a popular school-based running programme in the UK, is implemented in a diverse and multiethnic city in the UK and also the barriers faced by non-implementer schools., Design: Mixed method cross-sectional study (including survey data collection and qualitative interviews)., Setting: Primary schools in a multiethnic city in the East Midlands, UK., Participants: Forty-two schools in Leicester city completed an online survey, and five teaching staff from five schools took part in follow-up semistructured qualitative interviews., Results: Overall, 40.5% of schools who completed the survey reported having never implemented TDM, and 96.0% of implementer schools reported delivering TDM on three or more days per week. Reported barriers included space limitations and safety issues, timetabling and curriculum pressures, and pupil and teacher attitudes. Facilitators of implementation were teacher engagement and school culture/ethos, communication of the initiative and substantial delivery adaptations., Conclusions: The findings from this study, based on data from schools in a multiethnic city in the UK, suggest that implementation of TDM is variable, and is influenced by a range of factors related to the school context, as well as the characteristics of TDM itself., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351., Methods: Nonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge., Results: Eight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID 50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log 10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge., Conclusions: Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP., One-Sentence Summary: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Background: Patients with type 2 diabetes mellitus (DM), obesity, and chronic kidney disease (CKD) are generally physically inactive and may benefit from exercise. Our objective was to determine the effects of structured exercise on physical fitness, kidney function, endothelial function, inflammation, and body composition in such patients., Methods: In this randomized, controlled trial, 36 male patients (age 49-81) were randomly assigned to exercise + diet management (n = 18) or diet alone (n = 18). Participants were eligible if they had type 2 DM, body mass index >30 kg/m2, CKD stages 2-4, and persistent proteinuria (>200 mg/g creatinine for >3 months). The exercise intervention was a 12-week (3 days per week) program of aerobic and resistance training followed by 40 weeks of home exercise. The primary outcome measure was change from baseline in urine protein to creatinine ratio (UPCR) at 12 and 52 weeks., Results: Thirty-two participants completed the study (14 exercise + diet, 18 diet-alone group). The change from baseline in UPCR was slightly greater in the diet-alone group at 12 weeks but not at 52 weeks. Changes in both symptom-limited and constant-workrate treadmill times were significantly higher in the exercise + diet group at 12 weeks but not at 52 weeks. There were no significant differences in urine albumin to creatinine ratio, estimated glomerular filtration rate, endothelial function, inflammation, or body composition between the groups., Conclusions: In obese diabetic subjects with CKD, structured exercise improved exercise capacity but not body composition or renal function. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Purpose: The purpose of this study was to compare the effects of a 24-week walking with poles rehabilitation program with a traditional 24-week walking program on physical function in patients with peripheral arterial disease (PAD)., Methods: Patients with PAD (n = 103, age = 69.7 ± 8.9 years, ankle-brachial index < 0.90 or evidence of calcified vessels) were randomized into a rehabilitation program of traditional walking (n = 52) or walking with poles (n = 51). Patients exercised 3 times per week for 24 weeks. Exercise endurance was measured by time walked on a constant work rate treadmill test at 6, 12, and 24 weeks. Perceived physical function was measured by the Medical Outcomes Study Short Form-36 and Walking Impairment Questionnaire. Tissue oxygenation was measured using near-infrared spectroscopy., Results: Patients assigned to the traditional walking group walked longer at 24 weeks than those assigned to the pole walking group (21.10 ± 17.07 minutes and 15.02 ± 12.32 minutes, respectively, P = .037). There were no differences between the groups in tissue oxygenation. However, there was a significant lengthening of time for which it took to reach minimum tissue oxygenation values (P < .001) within the groups on the constant work rate test. There were no differences between the groups in perceived physical function as measured by the Physical Function subscale on the Medical Outcomes Study Short Form-36 or perceived walking distance as measured by the Walking Distance subscale on the Walking Impairment Scale., Conclusions: Traditional walking was superior to walking with poles in increasing walking endurance on a constant work rate treadmill test for patients with PAD.

Continuing uncertainty about the extent of the problem posed by Lyme borreliosis, the risk of serious sequelae, and unsatisfactory laboratory techniques to investigate it have led to the collaboration of researchers from 12 European Union (EU) countries a