The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target of neutralizing antibodies. Although they are infrequently elicited during infection or vaccination, antibodies that bind to the conformation-specific cryptic face of the RBD display remarkable breadth of binding and neutralization across . Here, we employed the immunofocusing technique PMD (protect, modify, deprotect) to create RBD immunogens (PMD-RBD) specifically designed to focus the antibody response toward the cryptic-face epitope recognized by the broadly neutralizing antibody S2X259.
View Article and Find Full Text PDFThe purpose of this technical report is to describe a modified tunnel surgical approach and connective tissue graft (CTG) stabilization technique for the treatment of gingival recessions with interproximal clinical attachment loss (ICAL). The partial-full-thickness (PFT) tunnel technique utilizes multiple vestibular incisions to facilitate creation of a split-mucoperiosteal tunnel that enhances tissue passivity and allows for coronal advancement of soft tissue with minimal tension. The supra-crestal sling (SCS) suture engages only the CTG, independent of the overlying tissue and stabilizes the CTG around the buccal and proximal root surfaces.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2024
The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from (EBOV)-one of three species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies.
View Article and Find Full Text PDFBackground: A previous case study reported periimplantitis and concomitant perigraftitis of a second implant placed at a site that had alveolar ridge preservation three decades earlier. Infection at the site persisted 4 months after implant removal by flapless implant reversal. A flap was subsequently reflected, the grafted bone was removed, and a second alveolar ridge preservation was performed with a freeze-dried bone allograft.
View Article and Find Full Text PDFThe pathways that induce macroautophagy (referred to as autophagy hereafter) in response to the stress of starvation are well conserved and essential under nutrient-limiting conditions. However, less is understood about the mechanisms that modulate the autophagy response. Here we present evidence that after induction of autophagy in budding yeast septin filaments rapidly assemble into discrete patches distributed along the cell cortex.
View Article and Find Full Text PDFEbola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from (EBOV) - one of three species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies.
View Article and Find Full Text PDFThe development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles.
View Article and Find Full Text PDFInt J Periodontics Restorative Dent
September 2024
This technical report describes the simplified subperiosteal sling (SPS) suture for connective tissue graft (CTG) stabilization in root coverage and phenotype modification of single and multiple reces- sion defects via the vestibular incisional subperiosteal tunnel access (VISTA). The simplified SPS suture engages only the CTG and stabilizes it to the tooth in the coronal-most position, inside the subperiosteal tunnel, independent of the overlying gingival tissue. The simplified SPS suture differs from the original SPS suture in that it engages the CTG first, and the needle and tail of the suture are knotted before the suture is introduced into the subperiosteal tunnel.
View Article and Find Full Text PDFWith the SARS-CoV-2 virus still circulating and evolving, there remains an outstanding question if variant-specific vaccines represent the optimal path forward, or if other strategies might be more efficacious towards providing broad protection against emerging variants. Here, we examine the efficacy of strain-specific variants of our previously reported, pan-sarbecovirus vaccine candidate, DCFHP-alum, a ferritin nanoparticle functionalized with an engineered form of the SARS-CoV-2 spike protein. In non-human primates, DCFHP-alum elicits neutralizing antibodies against all known VOCs that have emerged to date and SARS-CoV-1.
View Article and Find Full Text PDFInt J Periodontics Restorative Dent
November 2023
Although connective tissue grafts (CTGs) have been found to increase gingival thickness and reduce facial gingival recession in immediate implant placement and provisionalization (IIPP), they are associated with significant loss of buccal bone thickness. This loss is thought to be related to the preparation of the facial CTG recipient site. This technical report presents a modified dual-zone therapeutic concept in which the bone zone is grafted with bone graft and the tissue zone is grafted with tuberosity CTG without elevation of a facial partial- or full-thickness envelope.
View Article and Find Full Text PDFThis report describes the utilization of multiple subperiosteal sling (SPS) sutures to stabilize connective tissue grafts in the treatment of multiple recession defects using subperiosteal tunnels via vestibular and intrasulcular accesses. The SPS sutures engage only the graft and stabilize it against teeth inside the subperiosteal tunnel without engaging the overlying soft tissue, which is neither sutured nor coronally advanced. At sites with deep recessions, the graft is left exposed over the denuded root surfaces and allowed to epithelialize, which results in root coverage and increased attached keratinized tissue.
View Article and Find Full Text PDFWhile the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1.
View Article and Find Full Text PDFThe development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) performance in mice and (2) stability profiles.
View Article and Find Full Text PDFWhile the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1.
View Article and Find Full Text PDFFerritin-based, self-assembling protein nanoparticle vaccines are being developed against a range of viral pathogens, including SARS-CoV-2, influenza, HIV-1, and Epstein-Barr virus. However, purification of these nanoparticles is often laborious and requires customization for each potential nanoparticle vaccine. We propose that the simple insertion of a polyhistidine tag into exposed flexible loops on the ferritin surface (His-Fer) can mitigate the need for complex purifications and enable facile metal-chelate-based purification, thereby allowing for optimization of early stage vaccine candidates.
View Article and Find Full Text PDFVaccine scaffolds and carrier proteins increase the immunogenicity of subunit vaccines. Here, we developed, characterized, and demonstrated the efficacy of a novel microparticle vaccine scaffold comprised of bacterial peptidoglycan (PGN), isolated as an entire sacculi. The PGN microparticles contain bio-orthogonal chemical handles allowing for site-specific attachment of immunogens.
View Article and Find Full Text PDFIntroduction: Although alveolar ridge preservation may minimize alveolar ridge shrinkage following tooth extraction, there is a paucity of data on the effects of alveolar ridge preservation on implant-related outcomes. The purpose of this manuscript is to report on peri-implantitis of an implant placed at a site that had alveolar ridge preservation three decades earlier, and the subsequent dislodgement of an approximately 1-cm grafted bone specimen during degranulation 4 months after implant reversal.
Case Presentation: A 58-year-old male had #18 removed and the extraction socket grafted in the 1980s.
Introduction: Currently, inflammation of tissue around implants is diagnosed as either periimplant mucositis or periimplantitis, and the etiology is bacterial biofilm colonization of the implant and its transmucosal component. The purpose of this manuscript is to report a case of "periimplant mucositis" secondary to infection of a residual bone allograft embedded in the periimplant sulcus of a patient with diabetes.
Case Presentation: A #8 implant was placed and provisionalized in a 46-year-old male patient.
Introduction: Odontogenic fibroma is a rare benign neoplasm of mature fibrous connective tissue with variable amounts of inactive-looking odontogenic epithelium. Few recurrences of central odontogenic fibroma (COF) have been reported in the literature. This manuscript reports the enucleation of a recurrent COF and bone regeneration of the osseous defect with enamel matrix derivative and bone allograft.
View Article and Find Full Text PDFIntroduction: Periodontal regeneration of maxillary molar proximal furcation defects are challenging due to limited access. While combination therapy of open flap debridement with barrier membrane, bone graft, and biologics are reported to be more successful than monotherapeutic approaches, combination therapy can be complicated and costly.
Case Presentation: A total of four teeth in three patients are presented to demonstrate radiographic bone regeneration of deep Class 2 maxillary molar proximal furcation defects (MMPFD) treated with microscope-assisted papilla preservation technique (PPT) and demineralized freeze-dried bone allograft (DFDBA).
Int J Periodontics Restorative Dent
July 2019
This report describes a minimally invasive surgical approach using the vestibular incision subperiosteal tunnel access and a suture called the subperiosteal sling (SPS) to stabilize the connective tissue graft (CTG) for periodontal plastic surgery. The SPS suture engages only the CTG and stabilizes the CTG against the tooth independent of the overlying tissue, which minimizes the risk of graft mobility caused by muscle movement.
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