Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

Rademeyer, Cecilia,Korber, Bette,Seaman, Michael S.,Giorgi, Elena E.,Thebus, Ruwayhida,Robles, Alexander,Sheward, Daniel J.,Wagh, Kshitij,Garrity, Jetta,Carey, Brittany R.,Gao, Hongmei,Greene, Kelli M Public Library of Science 2016 PLoS pathogens Vol.12 No.7

<▼1><P>The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC<SUB>50</SUB> titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa.</P></▼1><▼2><P><B>Author Summary</B></P><P>Vaccine and passive immunization prophylactic trials that rely on antibody-mediated protection are planned for HIV-1 clade C epidemic regions of southern Africa, which have amongst the highest HIV-1 incidences globally. This includes a phase 2b trial of passively administered monoclonal antibody, VRC01; as well as a phase 3 trial using the clade C modified version of the partially efficacious RV144 vaccine. The extraordinary diversity of HIV-1 poses a major obstacle to these interventions, and our study aimed to determine the implications of viral diversity on antibody recognition. Investigations using our panel of very early viruses augment current knowledge of vulnerable targets on transmitted viruses for vaccine design and passive immunization studies. Evidence of antigenic drift with viruses becoming more resistant over time suggests that these prevention modalities will need to be updated over time and that combinations of antibodies will be necessary to achieve coverage in passive immunization studies. We further show that it may be more difficult to obtain protection in the genetically diverse clade C epidemic compared to RV144 where the epidemic is less diverse, although it should be noted that the correlates of infection risk are yet to be defined in the clade C setti

Encapsulation of Bifidobacterium adolescentis Cells with Legume Proteins and Survival under Stimulated Gastric Conditions and during Storage in Commercial Fruit Juices

Jiapei Wang,Darren R. Korber,Nicholas H. Low,Michael T. Nickerson 한국식품과학회 2015 Food Science and Biotechnology Vol.24 No.2

Highly acid-sensitive Bifidobacterium adolescentis (ATCC 15703) cells were entrapped in pea, soy, faba, and lentil protein-alginate capsules and subjected to challenge studies in synthetic gastric juice (SGJ, pH 2.5/37oC) and intestinal fluids (SIF, pH 6.5/37oC). B. adolescentis cells trapped in pea, soy, faba, and lentil protein-alginate capsules showed 1.9, 3.3, 5.1, and 5.5 log reductions in cell numbers, respectively after a 2 h challenge. Release of encapsulated B. adolescentis cells in SIF over 3 h indicated that after the first 10 min, almost all cells were released, regardless of the wall material. Storage of pea protein-based capsules was also tested in commercial orange, pineapple, and white grape juices at 4 and 22℃ for a 6-week duration. Encapsulated B. adolescentis cells survived in pineapple and white grape juice, but not in orange juice.

Anterior capsular reconstruction with acellular dermal allograft for subscapularis deficiency: a report of two cases

Raffy Mirzayan,Shane Korber 대한견주관절학회 2024 대한견주관절의학회지 Vol.27 No.1

Anterior glenohumeral instability with an irreparable subscapularis tear is a challenging problem for the orthopedic shoulder surgeon. Current techniques, including tendon transfers, yield inconsistent results with high rates of recurrent instability. Acellular dermal allografting has been used in young patients with massive superior rotator cuff tears with early success, but acellular dermal allografting is comparatively unstudied in anterior deficiency. We present two cases of anterior capsular reconstruction with an acellular dermal allograft in patients ages 66 and 58 years with irreparable subscapularis tendon tears. Follow-up for both patients exceeded 4 years, with forward flexion >140°, external rotation exceeding 60°, a Single Assessment Numeric Evaluation score >90 points, a visual analog scale score of 0 points, and an American Shoulder and Elbow Score of 98 points. In conclusion, acellular dermal allografting can be used to reconstruct the anterior capsule in patients with massive irreparable subscapularis tears, similar to its use in superior capsular reconstruction in patients with massive posterosuperior rotator cuff tears.

Optimization of Atmospheric Cold Plasma Treatment with Different Gases for Reduction of Escherichia coli in Wheat Flour

Lee, Jeongmin,Park, Seul-Ki,Korber, Darren,Baik, Oon-Doo The Korean Society for Microbiology and Biotechnol 2022 Journal of microbiology and biotechnology Vol.32 No.6

In this study we aimed to derive the response surface models for Escherichia coli reduction in wheat flour using atmospheric cold plasma (ACP) with three types of gas. The jet-type atmospheric cold plasma wand system was used with a 30 W power supply, and three gases (argon, air, and nitrogen) were applied as the treatment gas. The operating parameters for process optimization considered were wheat flour mass (g), treatment time (min), and gas flow rate (L/min). The wheat flour samples were artificially contaminated with E. coli at a concentration of 9.25 ± 0.74 log CFU/g. ACP treatments with argon, air, and nitrogen resulted in 2.66, 4.21, and 5.55 log CFU/g reduction of E. coli, respectively, in wheat flour under optimized conditions. The optimized conditions to reduce E. coli were 0.5 g of the flour mass, 15 min of treatment time, and 0.20 L/min of nitrogen gas flow rate, and the predicted highest reduction level from modeling was 5.63 log CFU/g.

Survival of probiotics in pea protein-alginate microcapsules with or without chitosan coating during storage and in a simulated gastrointestinal environment

Natallia Varankovich,Maria F. Martinez,Michael T. Nickerson,Darren R. Korber 한국식품과학회 2017 Food Science and Biotechnology Vol.26 No.1

Pea protein-alginate microcapsules with or without a chitosan coating and containing Lactobacillus rhamnosus R0011 and L. helveticus R0052 were produced by extrusion and tested for survivability during storage and in an in vitro gastrointestinal environment. Both microcapsule formulations provided significant protection for cells incubated in synthetic stomach juice at 37oC for 2 h, followed by 3 h in simulated intestinal fluid, relative to non-encapsulated bacteria. However, evaluation of cell viability during 9 weeks of storage at room temperature revealed that chitosan coating significantly improved microcapsule performance compared to non-coated microcapsules. Refrigerated storage had no negative impact on the microcapsule protection ability of both types of microcapsules. Notably, chitosan-containing microcapsules showed much higher bacterial survival counts during challenge tests even after storage. Moreover, the addition of chitosan to the microcapsule formulation did not increase the microcapsule size.

Bacterial Diversity and Composition of an Alkaline Uranium Mine Tailings-Water Interface

Nurul H. Khan,Viorica F. Bondici,Prabhakara G. Medihala,John R. Lawrence,Gideon M. Wolfaardt,Jeff Warner,Darren R. Korber 한국미생물학회 2013 The journal of microbiology Vol.51 No.5

The microbial diversity and biogeochemical potential associated with a northern Saskatchewan uranium mine watertailings interface was examined using culture-dependent and -independent techniques. Morphologically-distinct colonies from uranium mine water-tailings and a reference lake (MC)obtained using selective and non-selective media were selected for 16S rRNA gene sequencing and identification, revealing that culturable organisms from the uranium tailings interface were dominated by Firmicutes and Betaproteobacteria;whereas, MC organisms mainly consisted of Bacteroidetes and Gammaproteobacteria. Ion Torrent (IT) 16S rRNA metagenomic analysis carried out on extracted DNA from tailings and MC interfaces demonstrated the dominance of Firmicutes in both of the systems. Overall, the tailings-water interface environment harbored a distinct bacterial community relative to the MC, reflective of the ambient conditions (i.e., total dissolved solids, pH, salinity, conductivity,heavy metals) dominating the uranium tailings system. Significant correlations among the physicochemical data and the major bacterial groups present in the tailings and MC were also observed. Presence of sulfate reducing bacteria demonstrated by culture-dependent analyses and the dominance of Desulfosporosinus spp. indicated by Ion Torrent analyses within the tailings-water interface suggests the existence of anaerobic microenvironments along with the potential for reductive metabolic processes.