Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

The Human Immunodeficiency Virus type 1 (HIV-1) is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU) and Homosexual (Homo) risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs) are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries

Conformational HIV-1 Envelope on particulate structures: a tool for chemokine coreceptor binding studies

The human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 presents conserved binding sites for binding to the primary virus receptor CD4 as well as the major HIV chemokine coreceptors, CCR5 and CXCR4

Challenges in cancer vaccine development for hepatocellular carcinoma

SummaryHepatocellular carcinoma (HCC) is the most common liver malignancy, representing the third and fifth leading cause of death from cancer worldwide in men and women, respectively.The main risk factor for the development of HCC is the hepatitis B and C virus (HBV and HCV) infection; non-viral causes (e.g., alcoholism and aflatoxin) are additional risk factors.HCC prognosis is generally poor because of the low effectiveness of available treatments and the overall 5-year survival rate is approximately 5–6%.In this framework, immunotherapeutic interventions, including cancer vaccines, may represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that improvements in several aspects of the immunotherapy approaches need to be implemented.In particular, identification of novel specific tumor antigens and evaluation of most advanced combinatorial strategies could result in unprecedented clinical outcomes with great beneficial effect for HCC patients.The state of the art in immunotherapy strategies for HCC and future perspectives are reported in the present review

A Compensatory Liability Regime to Promote the Exchange of Microbial Genetic Resources for Research and Benefit Sharing

Female rhesus macaques were immunized with HIV virus-like particles (HIV-VLPs) or HIV DNA administered as sequential combinations of mucosal (intranasal) and systemic (intramuscular) routes, according to homologous or heterologous prime-boost schedules. The results show that in rhesus macaques only the sequential intranasal and intramuscular administration of HIV-VLPs, and not the intranasal alone, is able to elicit humoral immune response at the systemic as well as the vaginal level.funding agencies|Simian Vaccine Evaluation Unit (SVEU) of the Division of AIDS||European Community|201433|</p

Effects of adjuvants on IgG subclasses elicited by virus-like Particles

<p>Abstract</p> <p>Background</p> <p>Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model.</p> <p>Results</p> <p>Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced T_H2 pattern, VLPs formulated with either adjuvant elicited a T_H1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826.</p> <p>Conclusions</p> <p>The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.</p

A simple tool to measure spasticity in spinal cord injury subjects.

This work presents a wearable device and the algorithms for quantitative modelling of joint spasticity and its application in a pilot group of subjects with different levels of spinal cord injury. The device comprises light-weight instrumented handles to measure the interaction force between the subject and the physical therapist performing the tests, EMG sensors and inertial measurement units to measure muscle activity and joint kinematics. Experimental tests included the passive movement of different body segments, where the spasticity was expected, at different velocities. Tonic stretch reflex thresholds and their velocity modulation factor are computed, as a quantitative index of spasticity, by using the kinematics data at the onset of spasm detected through thresholding the EMG data. This technique was applied to two spinal cord injury subjects. The proposed method allowed the analysis of spasticity at muscle and joint levels. The obtained results are in line with the expert diagnosis and qualitative spasticity characterisation on each individual

Molecular and phylogenetic analysis of HIV-1 variants circulating among injecting drug users in Mashhad-Iran

Genetic and phylogenetic information on the HIV-1 epidemic in Middle-East Countries, and in particular in Iran, are extremely limited. By March 2004, the Iranian Ministry of Health officially reported a cumulative number of 6'532 HIV positive individuals and 214 AIDS cases in the Iranian HIV-1 epidemic. The intra-venous drug users (IDUs) represent the group at highest risk for HIV-1 infection in Iran, accounting for almost 63% of all HIV-infected population. In this regards, a molecular phylogenetic study has been performed on a sentinel cohort of HIV-1 seropositive IDUs enrolled at the end of 2005 at the University of Mashhad, the largest city North East of Tehran. The study has been performed on both gag and env subgenomic regions amplified by Polymerase Chain Reaction (PCR) from peripheral blood mononuclear cells (PBMCs) and characterized by direct DNA sequence analysis. The results reported here show that the HIV-1 subtype A is circulating in this IDUs sentinel cohort. Moreover, the single phylogenetic cluster as well as the intra-group low nucleotide divergence is indicative of a recent outbreak. Unexpectedly, the Iranian samples appear to be phylogenetically derived from African Sub-Saharan subtype A viruses, raising stirring speculations on HIV-1 introduction into the IDUs epidemic in Mashhad. This sentinel study could represent the starting point for a wider molecular survey of the HIV-1 epidemics in Iran to evaluate in detail the distribution of genetic subtypes and possible natural drug-resistant variants, which are extremely helpful information to design diagnostic and therapeutic strategies

Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). The HIV-VLP(A)s induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLP(A)s on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLP(A )stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLP(A)s at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers