Biology subjects

Regev-Yochay, G.

Publications and source records attributed to Regev-Yochay, G..

6 recordsLinked to original sources

bioRxiv2022

Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T-cell recognition epitopes

The continued evolution of the SARS-CoV-2 Omicron variant has led to the emergence of numerous sublineages with different patterns of evasion from neutralizing antibodies. We investigated neutralizing activity in immune sera from individuals vaccinated with SARS-CoV-2 wild-type spike (S) glycoprotein-based COVID-19 mRNA vaccines after subsequent breakthrough infection with Omicron BA.1, BA.2, or BA.4/BA.5 to study antibody responses against sublineages of high relevance. We report that exposure of vaccinated individuals to infections with Omicron sublineages, and especially with BA.4/BA.5, results in a boost of Omicron BA.4.6, BF.7, BQ.1.1, and BA.2.75 neutralization, but does not efficiently boost neutralization of sublineages BA.2.75.2 and XBB. Accordingly, we found in in silico analyses that with occurrence of the Omicron lineage a large portion of neutralizing B-cell epitopes were lost, and that in Omicron BA.2.75.2 and XBB less than 12% of the wild-type strain epitopes are conserved. In contrast, HLA class I and class II presented T-cell epitopes in the S glycoprotein were highly conserved across the entire evolution of SARS-CoV-2 including Alpha, Beta, and Delta and Omicron sublineages, suggesting that CD8+ and CD4+ T-cell recognition of Omicron BQ.1.1, BA.2.75.2, and XBB may be largely intact. Our study suggests that while some Omicron sublineages effectively evade B-cell immunity by altering neutralizing antibody epitopes, S protein-specific T-cell immunity, due to the very nature of the polymorphic cell-mediated immune, response is likely to remain unimpacted and may continue to contribute to prevention or limitation of severe COVID-19 manifestation.

immunology↗

bioRxiv2022

Enterobacteriaceae isolated from patients share antibiotic resistance conferring plasmids recently acquired from those isolated from sinks in the same treatment room

Identifying how and where pathogens acquire antibiotic resistance is crucial to developing effective strategies to limit its spread. Many bacterial species carry and share plasmids harboring antibiotic resistant genes. Plasmids are mobile genetic elements whose horizontal transmission is difficult to assess through genomic comparison due to assembly issues when using short-read sequencing alone. In this study, we use hybrid assembly to fully assemble plasmids that are shared between different Enterobacteriaceae isolated from patients and sinks in the same hospital rooms. We isolated and sequenced pairs of carbapenem resistant Enterobacter hormaechei subsp. xiangfangensis and Klebsiella pneumoniae from patients and sinks within the same hospital room. The isolate pairs share plasmids that putatively confer antibiotic resistance, including carbapenem resistance. These plasmids differ by few mutations and structural changes, while the isolates carry unique plasmids. Together, this suggests that plasmids can act as vectors of antibiotic resistance spread from sink reservoirs to patients.

microbiology↗

bioRxiv2020

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study

ObjectivesTo compare the burden of environmental shedding of toxigenic C. difficile among asymptomatic carriers, C. difficile infected (CDI) patients and non-carriers, in an inpatient non-epidemic setting. MethodsC. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatc patients. Active CDI was defined as a positive 2-step EIA/PCR test in patients with >3 unformed stools/24 hours. C. difficile environmental contamination was assessed by obtaining specimens from 10 sites in the patients rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. Results117 rooms were screened; 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (Control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which 3 (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of none carriers OR 12.23 and 11.16 (95%CI:1.5-99.96 P=0.0195, and 1.19-104.49 p=0.035), respectively. ConclusionHere we show that C. difficile carriers rooms are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

microbiology↗

bioRxiv2019

Patterns and predictors of Staphylococcus aureus carriage during the first year of life; a longitudinal study

ObjectivesTo determine the patterns of S. aureus carriage in the first year of life, its determinants and dynamics of transmission between mothers and infants.\n\nMethodsProspective longitudinal cohort study of S. aureus carriage among mothers and their infants. Monthly screenings from pregnancy/birth through the first year of the infants life. Medical and lifestyle data was collected. Infant S. aureus carriage was detected by rectal and nasal swabs and maternal carriage by nasal swabs. Multivariate analysis and an NLMixed model were used to determine predictors of carriage and S. aureus persistence.\n\nResults130 S. aureus carrier women and their 132 infants were included in the study. 93% of the infants acquired S. aureus sometime during the first year of life, 64% of them acquired the maternal strain, mostly (66%) during the first month of life. 70 women (52.50%) and 17 infants (14%) carried S. aureus persistently. Early acquisition of S. aureus carriage was associated with longer duration of initial carriage and was the most significant predictor of S. aureus persistence, while day-care center attendance was negatively associated with persistent carriage.\n\nConclusionsEarly acquisition of S. aureus, mostly from the mother, is an important determinant of carriage persistence in infancy.

epidemiology↗

bioRxiv2018

Comparison of early effects of PCV7, PCV10 and PCV13 on S. pneumoniae (SP) nasopharyngeal carriage in a population based study; the Palestinian-Israeli Collaborative Research (PICR)

BackgroundPneumococcal conjugate vaccines (PCVs), PCV10 and PCV13, are currently used in different countries. We have previously reported the effectiveness of PCV7, following its introduction in Israel and before PCVs were introduced in Palestine. Here, we extended the study and compared the initial impact of PCV10 to that of PCV7/13.\n\nMethodsFour cross-sectional surveys of S. pneumoniae carriage among children <5y through 2009-2014 were preformed among two proximate populations, living under two distinct health authorities, with different vaccination policies. In East-Jerusalem (EJ), PCV7 was implemented in 2009 and replaced by PCV13 in late 2010, while in Palestine (PA), PCV10 was implemented in 2011.\n\nResultsA total of 1267 and 2414 children from EJ and PA were screened. Implementation of both PCV7 (in EJ) and PCV10 (in PA) did not affect overall S. pneumoniae carriage ([~]30%), but resulted in a significant decrease in carriage of VT7 strains. In the pre-vaccine era, VT7/VT13 strains consisted 47.0%/62.0% and 41.2%/54.8% of pneumococci in EJ and PA, respectively. A 48.6% and 53.9% decrease was observed within 3 years of PCV7 implementation in EJ (p= 0.001) and PCV10 in PA (p<0.0001), respectively. These vaccination policies also resulted in [~]50% reduction in VT13-added serotypes especially 6A (from 11.0% to 0.0% (EJ) and 9.5% to 4.9% (PA)). Three years after PCV13 implementation in EJ, an additional 67% decrease in VT13 strains was observed, yet an increase in serotype 3 was observed (0.0% to 3.4%, p=0.056). The prevalence of non-VT13 strains increased during the study period from 38% and 45.3% to 89.8% and 70.7%, in EJ and in PA respectively.\n\nConclusionsWithin the first three years following PCV implementation, we observed similar reductions in carriage of VT10 and VT13 strains with either vaccination policies, with no effect on overall carriage. Further follow-up is needed to compare the long-term effects.

microbiology↗

bioRxiv2018

Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children

Vaccinating children with pneumococcal conjugate vaccines disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccination strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission. We used data from Israel to evaluate how the build-up of vaccine-associated immunity in children was associated with declines in IPD due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from a unique study conducted among children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on invasive pneumococcal disease in adults were obtained from a nationwide surveillance study. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the trajectory of decline of colonization prevalence and trajectory of increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage in children in the range of 36-59 months of age. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs.

epidemiology↗