Cellular Immune Responses Induced with Dose-Sparing Intradermal Administration of HIV Vaccine to HIV-Uninfected Volunteers in the ANRS VAC16 Trial

The objective was to compare the safety and cellular immunogenicity of intradermal versus intramuscular immunization with an HIV-lipopeptide candidate vaccine (LIPO-4) in healthy volunteers.A randomized, open-label trial with 24 weeks of follow-up was conducted in France at six HIV-vaccine trial sites. Sixty-eight healthy 21- to 55-year-old HIV-uninfected subjects were randomized to receive the LIPO-4 vaccine (four HIV lipopeptides linked to a T-helper-stimulating epitope of tetanus-toxin protein) at weeks 0, 4 and 12, either intradermally (0.1 ml, 100 microg of each peptide) or intramuscularly (0.5 ml, 500 microg of each peptide). Comparative safety of both routes was evaluated. CD8+ T-cell immune responses to HIV epitopes (ELISpot interferon-gamma assay) and tetanus toxin-specific CD4+ T-cell responses (lymphoproliferation) were assessed at baseline, two weeks after each injection, and at week 24.No severe, serious or life-threatening adverse events were observed. Local pain was significantly more frequent after intramuscular injection, but local inflammatory reactions were more frequent after intradermal immunization. At weeks 2, 6, 14 and 24, the respective cumulative percentages of induced CD8+ T-cell responses to at least one HIV peptide were 9, 33, 39 and 52 (intradermal group) or 14, 20, 26 and 37 (intramuscular group), and induced tetanus toxin-specific CD4+ T-cell responses were 6, 27, 33 and 39 (intradermal), or 9, 46, 54 and 63 (intramuscular). In conclusion, intradermal LIPO-4 immunization was well tolerated, required one-fifth of the intramuscular dose, and induced similar HIV-specific CD8+ T-cell responses. Moreover, the immunization route influenced which antigen-specific T-cells (CD4+ or CD8+) were induced.ClinicalTrials.gov NCT00121121

OA04-01. Safety and immunogenicity of LIPO-5, a HIV-1 lipopeptide vaccine: results of ANRS VAC18, a phase 2, randomized, double-blind, placebo-controlled trial

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Immune activation, smoking, and vaccine response

International audienceHere, we tested the hypothesis that chronic immune activation might fuel interindividual variability in vaccine response in the model of hepatitis B virus vaccine in HIV-1-infected adults. We observed that the marker of inflammation soluble tumour necrosis factor receptor I (sTNFRI) is predictive for vaccine efficiency. We also established that the link between tobacco smoking and impaired vaccine response might be mediated by inflammation. These data are a step forward in personalized vaccination

Long-term immunogenicity of two doses of 2009 A/H1N1v vaccine with and without AS03(A) adjuvant in HIV-1-infected adults.

International audienceOBJECTIVE: In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. DESIGN AND METHODS: In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. RESULTS: In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). CONCLUSION: In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination

Immune activation, smoking, and vaccine response

International audienceHere, we tested the hypothesis that chronic immune activation might fuel interindividual variability in vaccine response in the model of hepatitis B virus vaccine in HIV-1-infected adults. We observed that the marker of inflammation soluble tumour necrosis factor receptor I (sTNFRI) is predictive for vaccine efficiency. We also established that the link between tobacco smoking and impaired vaccine response might be mediated by inflammation. These data are a step forward in personalized vaccination

Long-term safety and vaccine-induced seropositivity in healthy volunteers from HIV vaccine trials

International audienceBackground: The ANRS COV1-COHVAC cohort was a long-term safety cohort of healthy volunteers who received preventive HIV-vaccine candidates in 17 phase I/II clinical trials.Methods: Data collected from the first vaccine candidate administration and annually after inclusion in the cohort included grade 3/4 adverse events and all grade adverse events suggestive of neurological, ophthalmological and immune disorders, self-administered questionnaires on behaviors and HIV ELISA results. Age-and-sex-standardized mortality ratios (SMRs) were calculated with respect to the French population. The cohort was early terminated in 2016 due to the absence of safety signal.Results: Of 496 volunteers, 488 were included: 355 in the 7-year prospective follow-up and 133 in the retrospective data collection only. The total follow-up after the first vaccination was 4934 person-years (median: 10 years) and 270 (76%) volunteers completed their follow-up. No relevant adverse event possibly related to the vaccine was reported. Breast cancer incidence and woman mortality did not differ from those of the French general population (standardized incidence ratio = 1.47, P = 0.45 and SMR = 0.65, P = 0.28, respectively) while man mortality was significantly lower (SMR = 0.26, P = 0.0003). At the last visit, 21/29 (72%) volunteers who received the recombinant HIV gp160 protein still showed vaccine-induced seropositivity after a median follow-up of 23 years. Only a few volunteers reported risky sexual practices (men: 20/192, women: 2/162).Conclusion: Volunteers showed a sustained high commitment. No long-term safety alert was identified during the postvaccine follow-up. Participating in vaccine trials did not increase risky behaviors for HIV infection. Vaccine-induced seropositivity may persist for more than 23 years after receiving rgp160

Evidence for glycosylphosphatidylinositol (GPI)-anchored eosinophil-derived neurotoxin (EDN) on human granulocytes

International audienceEosinophil-derived neurotoxin (EDN) is one of the four basic proteins stored in specific eosinophil granules. Here we demonstrate that EDN can also be detected at the surface of granulocytes. Reduction of EDN membrane expression after phosphatidylinositol-specific phospholipase C treatment suggests that a glycosylphosphatidylinositol (GPI) anchor is involved in the membrane association of EDN. The presence of a GPI anchor was confirmed by a lower expression of membrane EDN on granulocytes from patients with paroxysmal nocturnal hemoglobinuria which present cells lacking GPI anchor proteins. Furthermore, metabolic labeling with GPI anchor components supports biochemical evidence of GPI anchoring of EDN

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination

International audienceObjectives: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination.Methods: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves.Results: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection.Conclusion: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history

A comparison of Sars-Cov-2 vaccine platforms: the CoviCompare project

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