Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels.

Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.

Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2.

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.

Effect of bariatric surgery on obstructive sleep apnea and hypopnea syndrome, electrocardiogram, and pulmonary arterial pressure.

BACKGROUND: We evaluated the impact of surgically-induced weight loss on Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS), electrocardiographic changes, pulmonary arterial pressure and daytime sleepiness in morbidly obese patients. METHODS: 16 women and 13 men (n=29) underwent bariatric surgery in a 3-year period. The following tests were performed before and 1 year after surgery: nocturnal polysomnography, daytime Multiple Sleep Latency Test (MSLT), and echocardiogram. RESULTS: Mean age was 37.9+/-11 years (range 20-56). Preoperative body mass index was 56.5+/-12.3 kg/m(2) and it was 39.2+/-8.5 kg/m(2) at 13.7+/-6.6 months follow-up. Performed surgical procedures included: vertical banded gastroplasty in 6, Roux-en-Y gastric bypass in 12, and Distal Roux-en-Y gastric bypass in 11. Weight loss induced by surgery eliminated OSAHS in 46% of obese patients with an important improvement in oxygen saturation. Neck, thorax, waist and hip circumferences decreased significantly after surgical intervention but only neck circumference correlated significantly with the apnea/hypopnea index (Spearman rho=0.63, P <0.0001). Electrocardiographic abnormalities were present in 9 patients (31%) before surgery (sinus arrhythmia, ventricular arrhythmias, and sinus arrest). The number of electrocardiographic abnormalities decreased after surgery but new abnormalities appeared in some patients. Systolic pulmonary arterial pressure significantly decreased in the group of patients in whom OSAHS disappeared after surgery. Daytime sleepiness persisted after surgery in most patients. CONCLUSION: Bariatric surgery effectively reduces respiratory disturbances during sleep and improves pulmonary hypertension. Electro cardiographic abnormalities change after surgery. Daytime sleepiness appeared not to be related to respiratory disturbances during sleep.

[Ineffective motility in lower third of esophagus. Length of involved esophagus and severity of gastroesophageal reflux disease]. / Motilidad inefectiva en el tercio distal del esófago. Longitud del esófago afectado con relación a la gravedad de la enfermedad por reflujo gastroesofágico.

UNLABELLED: Ineffective esophageal motility (IEM) has been described in patients with gastroesophageal reflux disease (GERD). Exact prevalence of IEM is unknown; however, it is associated with more severe forms of GERD. There are no studies of IEM in patients with non-erosive GERD (NERD). Traditionally, IEM is identified by manometry at 3 and 8 cm above lower esophageal sphincter. Studies evaluating each cm of distal third of esophagus to detect IEM have not been carried out to date. AIM: To determine frequency of an IEM in NERD and erosive GERD as well as in mild and severe esophagitis, and to compare traditional criteria of IEM vs. manometry of each cm of distal third of esophagus. MATERIAL AND METHODS: Healthy controls and patients with NERD and mild and severe esophagitis were studied. Manometry of each cm of lower third of esophagus was performed. Amplitude of esophageal contractions and frequency of IEM were compared between different groups of subjects and patients. The ability to detect IEM by traditional criteria and proposed criteria was determined. RESULTS: Forty-four subjects were included, 13 controls, 10 patients with NERD, 12 with mild esophagitis, and nine with severe esophagitis. Amplitude of contractions was significantly different between groups. Controls showed higher amplitude than patients with severe esophagitis. Frequency of IEM was 0% in controls, 20% in NERD, 17% in mild esophagitis, and 33% in severe esophagitis. Frequency of IEM was similar when traditional criteria and proposed criteria were compared. CONCLUSIONS: IEM occurs in NERD as well as in mild and severe esophagitis, and IEM is associated with GERD severity. Traditional manometry detects similar proportion of patients with IEM as well as manometry of each cm of lower third of esophagus.