Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study

Langley, Joanne M.; Risi, George; Caldwell, Michael S.; Gilderman, Larry; Berwald, Bruce; Fogarty, Charles; Poling, Terry L.; Riff, Dennis; Baron, Mira; Frenette, Louise; Sheldon, Eric; Collins, Harry; Shepard, Marc; Dionne, Marc; Brune, D.; Ferguson, Linda; Vaughn, David W.; Li, Ping; Fries, Louis

doi:10.1093/infdis/jir172

Cited by 72 publications

(43 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the AS03 adjuvant present in some vaccines promotes immunogenicity by modulating the expression of local cytokines and by increasing the antigen loading in monocytes (17). Although this adjuvant has been safely administered with the H1N1 and the H5N1 strains to thousands of healthy adults (18), more data are needed about the potential for allosensitization among patients with renal disease. Indeed, many reports show that de novo occurrence of posttransplant anti-HLA Abs is associated with chronic rejection and graft loss (19 -21).…”

Section: Introductionmentioning

confidence: 99%

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

Broeders

Hombrouck²,

Lemy³

et al. 2011

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients.Design, setting, participants, & measurements Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: Ն4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. ResultsThe GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P Ͻ 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P Ͻ 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P ϭ 1, 1, and 0.39). ConclusionsThe influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

show abstract

Section: Introductionmentioning

confidence: 99%

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

Broeders

Hombrouck²,

Lemy³

et al. 2011

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Other trials have reported a low incidence of adverse effects (0%-3%) and no significant difference in serious adverse events between influenza vaccine and placebo. [15][16][17] Of the RCTs, FLUCAD 31 was likely the most well designed. The authors attempted to minimize bias and confounding through appropriate randomization, use of intention-to-treat analyses, and minimal loss to follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…14 However, in prospective randomized trials that included CV outcomes for safety assessment, influenza vaccination was not associated with a reduction in CV events, [15][16][17][18] although these trials were limited by low event rates and potential for misclassification. 19 Both the American Heart Association/American College of Cardiology and the European Society of Cardiology recommend the influenza vaccine annually for individuals with established CVD [20][21][22] without specifically stating that the purpose is to reduce the risk of CV events.…”

Section: Introductionmentioning

confidence: 99%

Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review

LeBras

Barry

2017

CJHP

View full text Add to dashboard Cite

RÉSUMÉContexte : La grippe est une infection courante des voies respiratoires qui peut causer des complications, notamment des événements cardiovasculaires. On a montré que la grippe double les risques d'infarctus du myocarde. De plus, les patients atteints d'une maladie cardiovasculaire sont les plus menacés. La vaccination contre la grippe a été associée à une réduction des cas d'infarctus du myocarde, de maladie cérébrovasculaire et de décès.Objectif : Évaluer les données probantes montrant que la vaccination contre la grippe permet de réduire le nombre d'événements cardiovasculaires chez les patients déjà atteints d'une maladie cardiovasculaire. Extraction et synthèse des données : Dix études répondaient aux critères de recherche (trois essais cliniques non aléatoires, cinq essais cliniques à répartition aléatoire et deux méta-analyses). Les essais cliniques non aléa-toires et les essais cliniques à répartition aléatoire présentaient des résultats variables en ce qui touche aux décès d'origine cardiovasculaire et aux événements cardiovasculaires indésirables. Les deux méta-analyses, qui avaient en commun quatre essais cliniques à répartition aléatoire concernant des patients atteints d'une maladie cardiovasculaire, montraient que le vaccin contre la grippe permettait de réduire le nombre de décès d'origine cardiovasculaire d'environ 50 % comparativement au groupe témoin. La vaccination a aussi réduit le nombre d'événements cardiovasculaires graves d'environ 43 %; le pourcentage était plus important (54 %) dans le sous-groupe de patients ayant récemment (à l'intérieur d'un an) souffert d'un syndrome coronarien aigu. Cependant, ces résultats sont potentiellement faussés par la petite taille des échantillons, les faibles taux d'événements et la variabilité avec laquelle on signale les résultats. Il y avait aussi une forte hétérogénéité clinique entre les études, ce qui pourrait ne pas être représentatif de la pratique actuelle. ABSTRACTBackground: Influenza is a common respiratory infection that may cause complications, including cardiovascular events. Influenza illness has been shown to double the risk of myocardial infarction, with the highest risk among patients with established cardiovascular disease. Vaccination against influenza has been associated with reductions in myocardial infarction, cerebrovascular disease, and death.

show abstract

“…6,[10][11][12] The pandemic experience created the unusual situation in which much of what we know about the immunological impact of AS03 is derived from human studies. This body of work has demonstrated that AS03-adjuvanted, dose-sparing formulations can induce strong serum antibody responses that persist for at least 12 months in healthy children, [13][14][15][16][17] adults [18][19][20][21][22][23] and the elderly, [24][25][26] and that influenza-specific, poly-functional CD4C T cells can be detected in human PBMC samples for at least 6 months after vaccination. [27][28][29] We have previously shown that AS03 can induce powerful humoral 6,12 and cellular responses 6 to influenza antigens over a surprisingly wide range of Ag doses (100-to 1000-fold lower than a 'standard' 3 mg HA dose in mice) at 3 weeks after a booster immunization The objective of this study was to determine the persistence of these responses up to 34 weeks after LD-AS03-adjuvanted vs. HD-unadjuvanted vaccination.…”

Section: Discussionmentioning

confidence: 99%

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Yam

Brewer

Bleau

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulation. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 mg hemagglutinin (HA)/ dose) or low-dose (LD) formulations (0.03 mg or 0.003 mg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibodysecreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4C T cells that express cytokines (IL-2, IFNg, TNFa and IL-5) by flow cytometry. All formulations elicited robust serum antibody titers that persisted for at least 34 weeks. The number of antigen-specific ASCs in the spleen and BM were higher in the 2 LD CAS03 groups, but despite having fewer ASCs, the average spot size in the HD-unadjuvanted group was larger at later time-points, suggesting greater antibody production per cell. Striking differences in the long-term profiles induced by the different vaccine formulations may contribute to these different ASC profiles. The HD-unadjuvanted vaccine elicited strong Th2 cytokines during the first 6 weeks pb but LDCAS03 groups generated broader, more durable responses at later timepoints. Finally, the 0.03 mg HACAS03 group generated the greatest number of antigen-specific CD4C T cells and the highest percentage of polyfunctional cells that expressed 2 or more cytokines. Although all of the tested vaccines induced durable antibody responses, we show that different vaccine formulations (dose-sparing, adjuvant) generate distinct long-term immune profiles. Furthermore, our data suggest that the different profiles may be generated through unique mechanisms.

show abstract

Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study

Cited by 72 publications

References 24 publications

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Contact Info

Product

Resources

About