Applying peptide antigens onto bare skin: induction of humoral and cellular immune responses and potential for vaccination.

The development of non-invasive immunisation procedures is a top priority for public health agencies when it is realised that the current immunisation practices are unsafe, particularly in developing countries due to the widespread reuse of non-sterile syringes. There is a risk of abscess formation resulting in impairment of meat quality or the value of the hide, and the risk of transmission of infectious diseases when vaccines are administered to food animals by injection. Recently, the skin has emerged as an alternative route for non-invasive delivery of vaccines. Topical application of various types of antigens (mainly proteins and toxoids) with an adjuvant resulted in the induction of systemic and mucosal immune responses. However, due to skin barrier constraints and the physicochemical properties of large molecular weight proteins, the immune responses are variable and require further optimisation. Small molecular size synthetic peptides when applied onto bare skin with an adjuvant are effective immunogens, inducing both humoral and cellular immune responses. Their use as vaccines offers considerable advantages over conventional preparations in terms of safety, purity, stability, availability and cost. Therefore, they could be the most suitable candidate immunogens for skin immunisation. This review describes our recent observations on the immunogenicity of synthetic peptides applied onto bare skin in relation to vaccination.     

Modal Analysis of the Ancillary During Femoral Stem Insertion: A Study on Bone Mimicking Phantoms

Annals of Biomedical Engineering - The femoral stem primary stability achieved by the impaction of an ancillary during its insertion is an important factor of success in cementless surgery....     

Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients

OBJECTIVE: Several lines of evidence suggest that the immune system may control HIV-1 replication, but that it could fail in the long term. Strategies aimed to elicit specific immune responses may enable patients to contain virus replication. METHODS: HIV-1-infected patients were randomized to continue either their antiviral therapy alone (controls; n = 37) or with four boosts of vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8, 12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32) (Vac-IL-2 group; n = 34). RESULTS: Of the Vac-IL-2 group, 15/32 (47%) exhibited a stable HIV p24 antigen-proliferative response compared with 8/33 (24%) controls (P = 0.049). After vaccination, 19/33 (58%) of the Vac-IL-2 group exhibited a multiepitopic HIV-1-specific CD4 cell proliferative response compared with 9/36 (25%) of controls (P = 0.006). The breadth and the magnitude of HIV-specific interferon-gamma-producing CD8 T cells improved in the Vac-IL-2 group. After stopping antiviral drugs, 24% of the Vac-IL-2 group lowered their viral set point compared with 5% of controls (P = 0.027). Logistic-regression analysis demonstrated that vaccine-elicited immunological responses were predictive of virological control (P = 0.046 and 0.014 for stable and multiepitopic CD4 T cell responses, respectively). CONCLUSION: This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.     

Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated control

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR(+) NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR(+) NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK-cell-mediated innate pressure.     

Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients

Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1^u to RT1^a). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-γ-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1^u determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.     

Movement irregularities in atypical parkinsonian syndromes

This study examined discrete motor irregularities in ballistic aiming movements in patients with atypical parkinsonian syndromes (APS). Nine patients with APS were compared to 9 patients with idiopathic Parkinson's disease (PD) and 9 controls on ballistic arm extension movements performed on a digitizing tablet without visual feedback and without accuracy constraints. Patients with APS showed a higher number of irregularities in the acceleration and jerk time series compared to PD patients and controls. No difference was found between PD patients and controls. These discrete irregularities were not associated with general motor impairment, tremor, akinesia, or rigidity. These results suggest that atypical parkinsonism is associated with movement irregularities in ballistic movements, which may help differentiate APS from PD.     

Type 1 and 2 gastric carcinoid tumors: long-term follow-up of the efficacy of treatment with a slow-release somatostatin analogue

Little is known about the long-term results of treating gastric carcinoid tumors with a slow-release somatostatin analogue. We report three patients with type 1 and 2 gastric carcinoid tumors who were treated in the above mentioned way and followed for 27-50 months. In all cases, alternative endoscopic or surgical management was considered but deemed inappropriate. Treatment with a slow-release somatostatin analogue was begun in light of a favorable recent report. The result was regression or complete disappearance of macroscopic fundal tumors. No side-effects were reported and, most notably, none of the patients developed gallstones. This small study may help define the optimal duration, dose, and administration interval of the treatment. Slow-release somatostatin analogue is a safe and efficacious treatment for type 1 and 2 gastric carcinoid tumors, and can be used when tumors are growing rapidly. Slow-release somatostatin analogue represents an alternative to repeated endoscopic treatment or high-risk surgery.