Superior efficacy of a human immunodeficiency virus vaccine combined with antiretroviral prevention in simian-human immunodeficiency virus-challenged nonhuman primates

International audienc

Rapid access to structured triacylglycerols acylated with n-3 polyunsaturated fatty acids for nutritional applications

International audienceIn order to better understand the metabolic fate of n-3 polyunsaturated fatty acids (PUFAs), an efficient access to symmetrical and unsymmetrical triacylglycerols (TGs), esterified with PUFAs, with known high purity, is required. In this context, we optimized the esterification of a mixture of glycerols protected as dioxane and dioxolane with PUFAs. The kinetics of this reaction depends on various factors, such as the fatty acid chain length and the stereochemistry of the dioxane. Then, one-pot acetal hydrolysis and esterification of hydroxyl groups led to the desired structured TGs without either double bond isomerization or acyl migration (except when symmetrical TGs are acylated with long-chain saturated fatty acids in external positions). PUFAs location on the glycerol backbone was assayed by NMR, HPLC and pancreatic lipase hydrolysis

The Fraction of a-Linolenic Acid Present in the sn-2 Position of Structured Triacylglycerols Decreases in Lymph Chylomicrons and Plasma Triacylglycerols during the Course of Lipid Absorption in Rats 1-3

International audienceLittle is known about the ability of a-linolenic acid (Ln) to remain in the sn-2 position of TG during the absorption process. The goal of this study was to determine the Ln distribution in the lymph (Study 1) and plasma (Study 2) TG of rats fed a single i.g. load of structured TG [300 mg/rat of either oleic acid (O)/Ln/O TG (OLnO) or Ln/O/O TG (LnOO), n = 7 rats]. In an early fraction (3-4 h) of lymph (OLnO group; 100%Ln in the sn-2 position), 46 6 2%Ln was maintained in this position in lymph TG. There was even less (29 6 6%) in the last fraction (7-24 h) (P , 0.05). Ln was also found (9 6 3%) in the sn-2 position of lymph TG in the LnOO group. The Ln content in lymph phospholipids was twice as high in rats when they were fed LnOO (4.2 6 0.1%) than OLnO (2.3 6 0.2%) (P , 0.005). Six hours postprandially (Study 2), 21 6 3% of the Ln incorporated into plasma TG was located in the sn-2 position in the OLnO group compared to 13 6 2%in the LnOO group (P , 0.001). Overall, these results indicate that the amount of Ln that moved fromthe sn-2 position of structured TG to the sn-1(3) position of lymph TG increased during absorption. This may account for a substantial hydrolysis of the 2-monolinolenylglycerols in enterocytes, leading to the intramolecular redistribution of Ln in lymph TG and, consequently, in plasma TG

Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative nanostructured lipid carriers as delivery systems: evidences in mice and non-human primates

Optimizing HIV p24 vaccine responses To date, HIV vaccines have resulted in poor or absent protection. A team led by Fabrice P. Navarro at the CEA LETI use the conserved HIV capsid protein p24 vectorized into cationic nanostructured lipid carriers (NLC-p24) along with NLC-delivered CpG. Owing to their small size, NLCs gain access to lymph nodes and deliver antigen directly to antigen presenting cells. Anti-p24 responses have been associated with effective HIV control, making them an attractive vaccine antigen, but they are poorly immunogenic. NLC-p24 shows a good safety profile while at the same time being able to elicit robust humoral and cellular immune responses in both mice and Cynomolgus macaques. NLC-mediated delivery of both p24 and CpG results in more effective immune stimulation than delivery of free antigen and adjuvant. These findings demonstrate the possibility of priming effective responses to a potent but otherwise poorly immunogenic HIV antigen

Timing of the last deglaciation in Lithuania

Boulders from the Gruda Moraine, which is associated with the maximum extent of the Scandinavian Ice Sheet (SIS) during the last glaciation, and the Baltija (also referred to as the South Lithuanian), the Middle and North Lithuanian moraines, which are associated with recessional stages of the SIS, were sampled for surface exposure dating using (10)Be. By combining these data with existing radiocarbon ages, we developed a chronology for the retreat of the SIS margin in Lithuania. Our new (10)Be ages suggest that the SIS margin began to retreat from its maximum extent at 18.3 +/- 0.8 (10)Be kyr. Based on a probable correlation of the Baltija Moraine with the Pomeranian Moraine in Poland, we infer that the Baltija Moraine was formed following a re-advance of the SIS margin. The ice margin retreated from the Baltija position at 14.0 +/- 0.4 (10)Be kyr. The SIS-margin retreat paused at least two more times to form the Middle Lithuanian Moraine at 13.5 +/- 0.6 (10)Be kyr and the North Lithuanian Moraine (tentatively correlated to the Pajuris Moraine) at 13.3 +/- 0.7 (10)Be kyr. Subsequent ice-margin retreat from the North Lithuanian Moraine represented the final deglaciation of Lithuania. Direct dating of these moraines better constrains the relation of ice-margin positions in Lithuania to those in adjacent countries as well as the SIS response to climate change

The works of Robert Louis Stevenson;

Half-title.I. New Arabian nights; The dynamiter.--II. Treasure Island; Kidnapped.--III. The black arrow; The merry men and other tales.--IV. Master of Ballantrae; Prince Otto.--V. An inland voyage; Travels with a donkey; The strange case of Dr. Jekyll and Mr. Hyde, etc.--VI. Memories and portraits; "Virginibus puerisque;" Memoir of Fleeming Jenkin.--VII. The South seas; Letters from Samoa, etc.--VIII. Stevenson as a poet [by E. Gosse]; Underwoods; A child's garden of verses, etc.--IX. Robert Louis Stevenson, by Leslie Stephen; Essays and reviews.--X. Familiar studies; Record of a family of engineers; Three letters.Mode of access: Internet.No.722 of 1000 numbered sets

A single lentivector DNA based immunization contains a late heterologous SIVmac251 mucosal challenge infection

Variety of conventional vaccine strategies tested against HIV-1 have failed to induce protection against HIV acquisition or durable control of viremia. Therefore, innovative strategies that can induce long lasting protective immunity against HIV chronic infection are needed. Recently, we developed an integration-defective HIV lentiDNA vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. A single immunization with such lentiDNA induced long-lasting T-cell and modest antibody responses in cynomolgus macaques. Here eighteen months after this single immunization, all animals were subjected to repeated low dose intra-rectal challenges with a heterologous pathogenic SIVmac251 isolate. Although the viral set point in SIVmac-infected cynomolgus is commonly lower than that seen in Indian rhesus macaques, the vaccinated group of macaques displayed a two log reduction of peak of viremia followed by a progressive and sustained control of virus replication relative to control animals. This antiviral control correlated with antigen-specific CD4+ and CD8+ T cells with high capacity of recall responses comprising effector and central memory T cells but also memory T cell precursors. This is the first description of SIV control in NHP model infected at 18 months following a single immunization with a non-integrative single cycle lentiDNA HIV vaccine. While not delivering sterilizing immunity, our single immunization strategy with a single-cycle lentivector DNA vaccine appears to provide an interesting and safe vaccine platform that warrants further exploration