ABSTRACT
BACKGROUND: Despite annual immunization, solid organ transplant (SOT) patients remain at increased risk for severe influenza infection because of suboptimal vaccine immunogenicity. We aimed to compare the CD4+ and CD8+ T-cell responses of the high-dose (HD) and the standard-dose (SD) trivalent inactivated vaccine. METHODS: We collected peripheral blood mononuclear cells pre- and postimmunization from 60 patients enrolled in a randomized trial of HD versus SD vaccine (30 HD; 30 SD) during the 2016-2017 influenza season. RESULTS: The HD vaccine elicited significantly greater monofunctional and polyfunctional CD4+ and CD8+ T-cell responses against influenza A/H1N1, A/H3N2, and B. For example, median vaccine-elicited influenza-specific polyfunctional CD4+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza A/H1N1 (1193 vs 0 per 106 CD4+ T cells; P = .003), A/H3N2 (1154 vs 51; P = .008), and B (1102 vs 0; P = .001). Likewise, vaccine-elicited influenza-specific polyfunctional CD8+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza B (367 vs 0; P = .002). CONCLUSIONS: Our study provides novel evidence that HD vaccine elicits greater cellular responses compared with the SD vaccine in SOT recipients, which provides support to preferentially consider use of HD vaccination in the SOT setting.
Subject(s)
Immunity, Cellular/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Humans , Immunocompromised Host/immunology , Immunogenicity, Vaccine , Influenza Vaccines/administration & dosage , Influenza, Human/virology , Male , Middle Aged , Organ Transplantation , Vaccine PotencyABSTRACT
Background: The annual standard-dose (SD) influenza vaccine has suboptimal immunogenicity in solid organ transplant recipients (SOTRs). Influenza vaccine that contains higher doses of antigens may lead to greater immunogenicity in this population. Methods: We conducted a randomized, double-blind trial to compare the safety and immunogenicity of the 2016-2017 high-dose (HD; FluzoneHD, Sanofi) vs SD (Fluviral, GSK) influenza vaccine in adult SOTRs. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay. Results: We enrolled 172 patients who received study vaccine, and 161 (84 HD; 77 SD) were eligible for analysis. Seroconversion to at least 1 of 3 vaccine antigens was present in 78.6% vs 55.8% in HD vs SD vaccine groups (P < .001), respectively. Seroconversions to A/ H1N1, A/H3N2, and B strains were 40.5% vs 20.5%, 57.1% vs 32.5%, and 58.3% vs 41.6% in HD vs SD vaccine groups (P = .006, P = .002, P = .028, respectively). Post-immunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group (P = .007, P = .002, P = .033). Independent factors associated with seroconversion to at least 1 vaccine strain were the use of HD vaccine (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.56-6.67) and use of mycophenolate doses <2 g daily (OR, 2.76; 95% CI, 1.12-6.76). Conclusions: HD vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population. Clinical Trials Registration: NCT03139565.
Subject(s)
Dose-Response Relationship, Immunologic , Influenza Vaccines/immunology , Transplant Recipients , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral , Antigens, Viral , Double-Blind Method , Female , Humans , Influenza Vaccines/administration & dosage , Male , Middle Aged , Organ Transplantation , Seroconversion , Young AdultABSTRACT
OBJECTIVES: To report the outcomes of patients who underwent Boston type 1 keratoprosthesis (Kpro) surgery at the University Health Network (Toronto, Ont.) and the University of Ottawa Eye Institute (Ottawa, Ont.) between June 2008 and July 2013. DESIGN: Retrospective case series. PARTICIPANTS: Forty-four eyes of 43 patients who underwent Kpro surgery. METHODS: A retrospective review was conducted of all Kpro procedures performed by 4 attending cornea surgeons. The preoperative characteristics and postoperative course of each patient were analyzed. RESULTS: In 31 eyes (70%), the primary indication for a Kpro was failed corneal transplantation. The remaining 13 eyes (30%) had Kpro as a primary procedure. In all eyes, preoperative visual acuity (VA) was 20/150 or worse, with 39 eyes (89%) having a VA of counting fingers, hand movement, or light perception. Mean follow-up time was 21 ± 12 months (range 12-57 months). The retention rate at the last follow-up was 95%. Best-achieved median VA was 20/100 (range 20/20 to no light perception [NLP]), with 37% of patients achieving a VA of >20/40 at some point during their postoperative course. At the last follow-up, median VA was 20/400 (range 20/30 to NLP). The 2 most common complications included retroprosthetic membrane formation (23 eyes, 52%) and elevated intraocular pressure (10 eyes, 23%). There were 5 cases (11%) of stromal melt and 1 case (2%) of infective keratitis. CONCLUSIONS: This study demonstrates that Kpro improves VA in a majority of cases, and is a viable option in situations in which there is a poor prognosis for traditional penetrating keratoplasty.
