Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif.

The HIV-1 gp41 Membrane Proximal External Region (MPER) is recognized by broadly neutralizing antibodies and represents a promising vaccine target. However, MPER immunogenicity and antibody activity are influenced by membrane lipids. To evaluate lipid modulation of MPER immunogenicity, we generated a 1-Palmitoyl-2-oleoylphosphatidylcholine (POPC)-based proteoliposome collection containing combinations of phosphatidylserine (PS), GM3 ganglioside, cholesterol (CHOL), sphingomyelin (SM) and the TLR4 agonist monophosphoryl lipid A (MPLA). A recombinant gp41-derived miniprotein (gp41-MinTT) exposing the MPER and a tetanus toxoid (TT) peptide that favors MHC-II presentation, was successfully incorporated into lipid mixtures (>85%). Immunization of mice with soluble gp41-MinTT exclusively induced responses against the TT peptide, while POPC proteoliposomes generated potent anti-gp41 IgG responses using lower protein doses. The combined addition of PS and GM3 or CHOL/SM to POPC liposomes greatly increased gp41 immunogenicity, which was further enhanced by the addition of MPLA. Responses generated by all proteoliposomes targeted the N-terminal moiety of MPER overlapping the 2F5 neutralizing epitope. Our data show that lipids impact both, the epitope targeted and the magnitude of the response to membrane-dependent antigens, helping to improve MPER-based lipid carriers. Moreover, the identification of immunodominant epitopes allows for the redesign of immunogens targeting MPER neutralizing determinants.

Bone Remodeling around Implants Placed in Augmented Sinuses in Patients with and without History of Periodontitis.

BACKGROUND: Susceptible individuals may be more prone to bone loss after augmentation procedures. PURPOSE: Identify plausible clinical and biological factors influencing apical and marginal bone remodeling at implants placed in augmented sinuses, in patients with and without history of periodontitis. MATERIALS AND METHODS: This prospective cross-sectional clinical study analyzed implant bone levels in a group of 104 patients with and without history of periodontitis undergoing 139 sinus augmentation procedures. Marginal and apical bone loss (MBL/ABL) was measured post-loading using a standardized digital technique. Measurements were taken preoperatively, at second stage implant uncovery, one year after loading and at an average of 53-months follow-up. Odds ratios were calculated to evaluate risks factors of contributing variables, such as, smoking, history of periodontitis, membrane perforation, surgical approach, grafting material, use of PRP, and implant design/dimensions. RESULTS: Patients with history of periodontitis were 8.43 times more likely to present more than 2mm of MBL than patients without it (p =.041; CI95%: 1.09-65.12). Smokers were 4.97 times more likely to present over 2 mm of MBL than non-smokers (p =.003; CI95%: 1.70-14.54). Sinus membrane perforations were 11.4 times more likely to present ABL than those without perforation (p = 0.007; CI95%: 1.94-66.93). Mean MBL/ABL after 1-year post-loading and at last control were 0.49/0.56 mm and 0.67/0.46 mm, respectively. The use of a collagen membrane to cover the antrostomy and only xenograft as grafting material decreased ABL by 0.9 mm. The combination of autologous/xenograft bone was 4.04 times more likely to present higher ABL than xenograft alone (p = 0.023; CI95%: 1.21-13.45). Overall implant survival/success rates were 94.39%/91.33%, respectively. CONCLUSIONS: Smoking and previous history of periodontitis negatively affects implant MBL. Sinus membrane perforation was associated with higher ABL. Lack of association between bone remodeling at marginal and apical areas suggests that they are different and independent processes.