Veronique Bachy

Publications of Veronique Bachy

• Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1.

  Authors: Adel Benlahrech, Julian Harris, Andrea Meiser, Timos Papagatsias, Julia Hornig, Peter Hayes, Andre Lieber, Takis Athanasopoulos, Veronique Bachy, Eszter Csomor, Rod Daniels, Kerry Fisher, Frances Gotch, Len Seymour, Karen Logan, Romina Barbagallo, Linda Klavinskis, George Dickson, Steven Patterson

  Proceedings of the National Academy of Sciences of the United States of America. 11/2009;

  In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-gamma production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.

• Mouse vaccination with dendritic cells loaded with prion protein (PrP) peptides overcomes tolerance and delays scrapie.

  Authors: Veronique Bachy, Clara Ballerini, Pauline Gourdain, Aurelie Prignon, Saci Iken, Nadine Antoine, Martine Rosset, Claude Carnaud

  The Journal of general virology. 10/2009;

  Prion diseases are presumably caused by the accumulation in the brain of a pathological protein called prion protein scrapie which results from the transconformation of cellular PrP, a ubiquitousPrion diseases are presumably caused by the accumulation in the brain of a pathological protein called prion protein scrapie which results from the transconformation of cellular PrP, a ubiquitous glycoprotein expressed in all mammals. Since all isoforms of PrP are perceived as self by the host immune system, a major problem in designing efficient immunoprophylaxis or immunotherapy is to overcome tolerance. The present study was aimed at seeing whether bone-marrow-derived dendritic cells loaded with peptides previously shown to be immunogenic in PrP-deficient mice, can overcome tolerance in PrP-proficient wild type mice and protect them against scrapie. Results show that peptide-loaded dendritic cells elicit in such mice both lymphokine release by T cells and antibody secretion against native cellular PrP. Repeated recalls with peptide-loaded dendritic cells reduces the attack rate of 139A scrapie inoculated i.p. and retards by 40 days disease duration. Most interestingly, survival time in individual mice appears to be correlated with the level of circulating antibody against native cellular PrP.