The 2009 pandemic influenza A (H1N1) virus spread rapidly throughout Brazil. Non-adjuvanted and the adjuvanted influenza A H1N1/09 monovalent vaccine were recommended as a single dose to persons at risk including renal transplant recipients (RTR). We analyzed the safety and the immune response of 2 influenza A H1N1/09 monovalent vaccines in RTR, and identified factors influencing the immune response.
A total of 78 RTR received a single dose of either influenza A H1N1 2009 monovalent AS03-adjuvanted vaccine or a non-adjuvanted vaccine, and 58 healthy controls received a single dose of non-adjuvanted vaccine. Antibody responses to influenza A H1N1 were measured by hemagglutination inhibition assay and were compared between groups on the day of vaccination and 21-30 days thereafter, using geometric mean titer (GMT), and seroprotection (SP) and seroconversion (SC) rates.
Among RTR, after adjuvanted and non-adjuvanted H1N1 vaccination, the SP rate increased from 16.7% to 61.7% (P < 0.001) and to 50% (P < 0.001), and SC rates were 61.7% and 50%, respectively. For healthy controls, SP rate increased from 25.8% to 89.7% (P < 0.001), and SC rate was 87.9% after vaccination. Pre-vaccination GMT for the adjuvanted and non-adjuvanted RTR vaccine groups and healthy controls was 9.7 (95% confidence interval [CI] 7.3-13.1), 8.9 (95% CI 5.4-14.7), and 12.5 (95% CI8.7-18.2), and significantly increased to 49.8 (95% CI 31.3-79.4, P < 0.001), 43.2 (95% CI 16.3-114.4, P < 0.001), and 323.8 (95% CI 213.9-490.2, P < 0.001), respectively. Deceased-donor type transplant significantly reduced SP (odds ratio [OR] = 4.62, 95% CI 1.36-15.69, P = 0.014) and SC (OR = 6.29, 95% CI 1.89-20.98, P = 0.003) rates, and younger age positively affected SP (OR = 0.11; 95% CI 0.03-0.04, P = 0.001). Adverse events were mild, and renal function showed no change post vaccination.
RTR vaccinated with either an adjuvanted or non-adjuvanted monovalent influenza vaccine presented poor response compared with healthy controls. Post-vaccination adverse events were mild, and no rejection episode or renal dysfunction was observed.
"From the available data, the longer and more pronounced history of immunodeficiency of the patient with HIV, rather than the cross-sectional value of the CD4 before vaccination  , has been shown to influence the vaccine response. For the KT population who were conceptually immunodeficient, several factors potentially reduced the IG to the vaccine, consisting of patients' older age , deceased donor , use of mycophenolate   or mammalian target of rapamycin (m-TOR) inhibitor , and shorter time to vaccination post-KT  . Strategies to improve the immune response to the vaccine have remained the topic of current interest and ongoing research. "
[Show abstract][Hide abstract] ABSTRACT: Background
Data on the immunogenicity (IG) of the influenza vaccine among patients at high risk of influenza-related complication are limited.
We studied the antibody titer following a single dose of monovalent 2009 influenza A (H1N1) vaccine between groups of adult patients who were healthy, those with chronic renal failure (CRF), kidney transplant (KT) recipients, and human immunodeficiency virus (HIV)-infected patients. The IG (primary endpoints) was accessed at 4 weeks after vaccination. The secondary endpoint was safety of the vaccine.
A total of 293 patients were studied. Patients' mean age was 41(standard deviation [SD], 13.3) years old. At baseline, mean age (P < .001), history of vaccination in a prior year (P < .001), and geometric mean titers (GMT; P < .001) significantly differed between each groups and the majority (70%) of participants had the hemagglutination inhibition titer <1:10. The IG of the vaccine was highest in the healthy group (71.4 %). The response rate among CRF, KT, and HIV groups was 42.4% (risk ratios [RR], 0.72; 95% confidence interval [CI], 0.5–1.02), 31.9% (RR, 0.51; 95% CI, 0.34–0.76), and 29.7% (RR, 0.42; 95% CI, 0.3–0.6), respectively. The vaccine was well-tolerated in all studied groups. Thirty (10.2%) patients experienced at least 1 adverse reaction but systemic reaction was uncommon (3.4%).
A single dose of monovalent 2009 influenza A (H1N1) vaccine result in poor IG among high-risk populations, including CRF, KT and HIV patients.
[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
To highlight the latest evidence for the use of key vaccines that are recommended in organ transplant candidates and recipients.
Influenza vaccine is the best studied vaccine; factors affecting immunogenicity of this vaccine include time from transplant, use of mycophenolate mofetil and type of transplant. Newer formulations of influenza vaccine are available, but data for these are limited. Updated recommendations include giving conjugated pneumococcal vaccine to adult transplant candidates and recipients followed by the polysaccharide vaccine to increase serotype coverage. Human papillomavirus vaccine should also be given to transplant recipients, although the immunogenicity may be suboptimal. Quadrivalent meningococcal conjugate vaccine needs to be given in special circumstances such as to patients who are starting eculizumab therapy. Live vaccines in general are contraindicated, although increasing safety data are emerging for Varicella vaccine. Herpes Zoster vaccine may be offered prior to transplant, although the utility of this strategy regarding protection from shingles after transplant is not known. Newer vaccines such as inactivated zoster vaccine and vaccines for the prevention of cytomegalovirus are under study.
Immunization for organ transplant recipients is an important part of pretransplant evaluation and the long-term care of the transplant recipient.
Current Opinion in Infectious Diseases 06/2014; 27(4). DOI:10.1097/QCO.0000000000000078 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Author Summary
Infection with influenza viruses is associated with high morbidity and mortality. Therefore, vaccination is recommended in immunosuppressed patients, however often the post-vaccine induced protection is insufficient. Factors associated with reduced vaccine responses may guide preventive strategies and could offer novel targets for adjuvants. Here, we explore the impact of IL-28B on B- and T-cell responses during vaccination. We found that a single nucleotide polymorphism (minor allele genotype) in the IL-28B gene was associated with a significant increase in the antibody seroconversion rate following influenza vaccination. Interestingly, this SNP reduces the expression of IL-28B. In addition, in vitro stimulation of peripheral blood mononuclear cells from patients with the SNPs had increased IL-4 production in CD4 T-cells. As a potential mechanism, we show that recombinant IL-28B inhibits influenza stimulated Th2 cytokine release, B-cell activation/prol
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