Safety and Immunogenicity of a Genetically Engineered Human Immunodeficiency Virus Vaccine

A phase 1 trial of a candidate human immunodeficiency virus type 1 (HIV-I) vaccine was done in 25 healthy seronegative subjects. The antigen, env2-3 (SF2), was a nonglycosylated polypeptide representing the gp120 region of the env gene of the HIV-l(SF2) isolate. It was produced in genetically engineered yeast as a denatured molecule incapable of binding CD4. A synthetic lipophilic muramyl tripeptide (MTP-PE) was used as an adjuvant. Ten subjects received adjuvant alone and 15 received 50- or 25O-µg doses of env2-3 (SF2) administered intramuscularly in two immunization regimens. In general, adjuvant and vaccine were well tolerated. Antibody responses to both the homologous antigen, env2-3 (SF2), and antigens from other highly divergent HIV isolates were elicited in the majority of vaccine recipients. However, antibody titers were low, without neutralizing activity. In 9 of 11 subjects who received the complete vaccine immunization series, a significant specific T lymphocyte response was observe

Comportements de subsistance paléolithiques et relations entre l’Homme et les Carnivores à la grotte aux Points (Aiguèze, Gard) au travers de l’archéozoologique et taphonomique des restes fauniques

International audienc

Faunes paléolithiques des Peyrugues à Orniac, Lot

National audienc

HLA antigens are risk factors for development of AIDS

HLA-A, -B, -C, -DR, and -DQ antigens were determined by serology and in cases of severe lymphopenia by RFLP-DNA typing in 51 Caucasians with a diagnosis of AIDS (32 with opportunistic infections and 19 with secondary cancers). In addition, 86 HIV-1 seropositive and 39 HIV-1 seronegative drug abusers and 148 healthy controls were also studied. No significant differences in HLA antigen frequencies were found in comparison of HIV-1 seropositive and HIV-1 seronegative drug abusers with controls, suggesting that HLA polymorphism does not represent a genetic risk for infection with HIV-1. In contrast, a significant increased frequency of B35 (p less than 0.01) and CW4 (p less than 0.01) was observed in both groups of AIDS patients as compared to controls. Moreover, DR2 was increased in frequency in patients with opportunistic infections (p less than 0.01) and DR3 was completely absent in patients with secondary cancers (p less than 0.05). In the latter group, the DR5 frequency was increased, although nonsignificantly. These findings provide strong evidence for the existence of HLA-linked factors of susceptibility and host resistance to AIDS

Hautes doses d'immunoglobulines par voie intraveineuse pour le traitement des neutropénies "auto-immunes"

Two patients respectively with acute agranulocytosis and with chronic neutropenia were treated with high-dose immunoglobulins. In the first case, immunologic tests revealed the presence of antigranulocytic autoantibodies: all other tests (antinuclear antibodies, anti-DNA antibodies, immune complexes, latex) were negative. In the second case, all the above mentioned tests were negative. In both patients, neutrophil number returned to normal after the second immunoglobulin injection. Eight months after treatment, the neutrophil count was normal in the first patient and anti-granulocyte tests had become negative. In the second patient there was a late recurrence of neutropenia. The diagnosis of autoimmune neutropenia is difficult to confirm. In the case of peripheral "idiopathic" neutropenia, with infectious complications, high-dose immunoglobulin administration thus appears justified regardless of the results of the immunologic tests. This therapy also has the advantage of avoiding side effects of steroid treatment or of splenectomy

HLA-DPB1 DNA polymorphism in the Swiss population : linkage disequilibrium with other HLA loci and population genetics affinities

Allelic diversity at the HLA-OPBl locus was determined by PCR-oligotyping in a sample of 125 healthy Swiss individuals. A total of 17 alleles were detected among which four main alleles (DPBP1*0401, *0201, *0301, *0402) reached a cumulative frequency 0f 74.8%. HLA-A and -B (by serology) and HLA-DRBl (by oligotyping) allelic pOlymorphisms were analysed also. HLA-B and HLA-DRBl loci were highly polymorphic with 25 and 28 alleles respectively and similar heterozygosity levels of 0.93 and 0.92. These two loci were found to be more polymorphic than expected under neutrality, while lower heterozygosity levels were found for HLA-A (0.87) and DPB 1 (0.81) loci. This paper presents also a global comparison of DPBl allelic frequencies among 15 populations from four continents. As opposed to the DRBl locus, overall DPB1 is shown to have a lower level of polymorphism and may be considered as neutral in all tested populations. DPB1 genetic diversity is correlated significantly with geography also, as found previously for DRBl. Two- and four-locus haplotype frequencies were determined and the significance of their linkage disequilibrium tested by an original non-parametric method. A significant positive linkage disequilibrium was found for 11 A-B, 16 B-DRB1, 7 DRBI-DPBl and 3 A-B-DRBI-DPBl haplotypes. The overall linkage disequilibrium between DRB1 and DPB1 was much lower than expected from the physical distance and lower than for A-B and B-DRB 1 pairs. The implications of these results for bone marrow transplantation and for the evolution of HLA loci are discussed

Comparative efficacy of repetitive nerve stimulation, exercise, and cold in differentiating myotonic disorders.

The decremental response of the compound muscle action potential (CMAP) to provocative tests is not characterized in genetically verified myotonic disorders. We therefore studied the relationship between decremental responses and mutation type in 10 patients with recessive myotonia congenita (rMC), two with paramyotonia congenita (PMC), nine with myotonic dystrophy type 1 (DM1), four with DM2, and 14 healthy people. CMAPs were measured at rest, just after a short exercise test (SET), and during short, 5- and 10-HZ, repetitive nerve stimulation (RNS) trains at 32 degrees C and at 20 degrees C. The degree of decrement was not related to the severity of clinical myotonia. Controls and PMC patients had similar responses when warm, but with cooling PMC patients had a persistent decrement of CMAPs. In the rMC patients the decremental responses were related to the type of mutation of the CLCN1 gene, as a decrement was encountered in the T268M, R894X, IVS17+1 G>T, K248X, and 2149 del G, but not with the IVS1+3 A>T, F167L, or dominant A313T mutations. In DM1 patients there was no relationship between decrement and CTG repeats. The degree of partial inexcitability in myotonic muscle membrane therefore depends on the mutation type rather than degree of clinical myotonia. RNS at 10 HZ is more sensitive than SET for demonstrating abnormalities in rMC patients when warm; differences are less marked when cold, which is useful to diagnose PMC. Provocative tests are therefore useful in myotonias to demonstrate muscle inexcitability, which depends on the chloride or sodium channelopathy