CD4+ T Cell Depletion in Human Immunodeficiency Virus (HIV) Infection: Role of Apoptosis

Human immunodeficiency virus (HIV) infection is principally a mucosal disease and the gastrointestinal (GI) tract is the major site of HIV replication. Loss of CD4+ T cells and systemic immune hyperactivation are the hallmarks of HIV infection. The end of acute infection is associated with the emergence of specific CD4+ and CD8+ T cell responses and the establishment of a chronic phase of infection. Abnormal levels of immune activation and inflammation persist despite a low steady state level of viremia. Although the causes of persistent immune hyperactivation remain incompletely characterized, physiological alterations of gastrointestinal tract probably play a major role. Failure to restore Th17 cells in gut-associated lymphoid tissues (GALT) might impair the recovery of the gut mucosal barrier. This review discusses recent advances on understanding the contribution of CD4+ T cell depletion to HIV pathogenesis

Identification of Cryptic MHC I–restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses

Pediatric Measles Vaccine Expressing a Dengue Antigen Induces Durable Serotype-specific Neutralizing Antibodies to Dengue Virus

Dengue disease is an increasing global health problem that threatens one-third of the world's population. Despite decades of efforts, no licensed vaccine against dengue is available. With the aim to develop an affordable vaccine that could be used in young populations living in tropical areas, we evaluated a new strategy based on the expression of a minimal dengue antigen by a vector derived from pediatric live-attenuated Schwarz measles vaccine (MV). As a proof-of-concept, we inserted into the MV vector a sequence encoding a minimal combined dengue antigen composed of the envelope domain III (EDIII) fused to the ectodomain of the membrane protein (ectoM) from DV serotype-1. Immunization of mice susceptible to MV resulted in a long-term production of DV1 serotype-specific neutralizing antibodies. The presence of ectoM was critical to the immunogenicity of inserted EDIII. The adjuvant capacity of ectoM correlated with its ability to promote the maturation of dendritic cells and the secretion of proinflammatory and antiviral cytokines and chemokines involved in adaptive immunity. The protective efficacy of this vaccine should be studied in non-human primates. A combined measles–dengue vaccine might provide a one-shot approach to immunize children against both diseases where they co-exist

CD4+ T Cell Depletion in Human Immunodeficiency Virus (HIV) Infection: Role of Apoptosis

Human immunodeficiency virus (HIV) infection is principally a mucosal disease and the gastrointestinal (GI) tract is the major site of HIV replication. Loss of CD4+ T cells and systemic immune hyperactivation are the hallmarks of HIV infection. The end of acute infection is associated with the emergence of specific CD4+ and CD8+ T cell responses and the establishment of a chronic phase of infection. Abnormal levels of immune activation and inflammation persist despite a low steady state level of viremia. Although the causes of persistent immune hyperactivation remain incompletely characterized, physiological alterations of gastrointestinal tract probably play a major role. Failure to restore Th17 cells in gut-associated lymphoid tissues (GALT) might impair the recovery of the gut mucosal barrier. This review discusses recent advances on understanding the contribution of CD4+ T cell depletion to HIV pathogenesis

Est-il envisageable d'utiliser le vaccin vivant atténué contre la rougeole comme vecteur de vaccination pédiatrique bivalent ?

Live-attenuated measles vaccine is one of the best human vaccines available. During the 30 last years, it has been given to hundreds of million of children and shown to be highly efficacious and safe. This vaccine induces a life-long immunity to reinfection after a single or two low-dose injections. It is easily produced on a large scale in most countries and can be distributed at low cost. Reversion to pathogenicity has never been observed. For these favorable characteristics, measles vaccine might be a very promising paediatric vector to immunize children against both measles and other viral infections like AIDS or flaviviroses in the developing world. To this end, we developed a replicating vector derived from the Schwarz attenuated vaccine strain of measles virus. We showed the capacity of this vector to strongly and stably express proteins from Human Immunodeficiency virus (HIV) or West Nile virus (WNV). This vector induces specific immune reponses against the heterologous antigens in vivo that, in the case of West Nile virus, are able to protect the animals from an experimental challenge. This work led to the setting of phase I/II clinical trials intended to evaluate the capacities of this vector to induce specific HIV immune reponses in adults with pre immunity against measles.Le vaccin antirougeoleux compte parmi les meilleurs vaccins disponibles. Au cours des trente dernieres années, il a été adminis- tré à des centaines de millions d'enfants et a montré son efficacite et son innocuité. Ce vaccin vivant attenué induit une immunité vie après une seule ou deux injections. II est facilement produit grande échelle dans de nombreux pays et il est distribue et bas prix. Ces caracteristiques favorables nous ont conduits à envisager son utilisation comme vecteur pediatrique pour simultanément proteger les enfants de la rougeole et les immuniser contre d'autres infections virales comme le sida ou les flaviviroses. Dans ce but, nous avons développé un vecteur vivant derive de la souche vaccinale attenuee Schwarz du virus de la rougeole. Nous avons montre que ce vecteur pouvait exprimer de maniere forte et stable des protéines du virus de I'immunodéficience humaine (VlH) et du virus du Nil occidental. Ce vecteur permet I'induction in vivo de reponses immunes specifiques capables, dans le cas du virus du Nil occidental, de proteger d'une épreuve expérimentale. Ces travaux ont amene à la mise en projet d'essais cliniques de phase I et IIII destinés à tester chez I'homme les capacit6s de ce vecteur à induire des réponses immunes spécifiques du VlH chez des adultes prealablement immunises contre la rougeole

La statuaire

International audienc

La statuaire

International audienc