Monovalent H1N1 Research Articles

Safety of Vaccines Used for Routine Immunization in the United States.

To conduct a systematic review of the literature on the safety of vaccines recommended for routine immunization of children, adolescents, and adults in the United States as of 2011. We included placebo-controlled clinical trials and cohort studies comparing vaccinated and unvaccinated patients. We also included the following types of post-licensure analyses: case-control studies, self-controlled case series, and multivariate risk factor analyses. We conducted an electronic search of PubMed from inception through August 2013, and reviewed Advisory Committee for Immunization Practices statements, vaccine package inserts, and previously published reviews to identify studies. Scientific Information Packets were requested from vaccine manufacturers. We reviewed the methodology of the 2011 Institute of Medicine (IOM) consensus report "Adverse Effects of Vaccines: Evidence and Causality" and accepted their findings. We augmented their work with new studies and additional vaccines. For studies not included in the IOM report, we abstracted data on the presence or absence of adverse health outcomes, characteristics of patients, study design, and vaccine description, including brand, potency, dosage, timing, and formulation, where available. We excluded formulations not used in the United States. The McHarm instrument was used to evaluate the quality of adverse events collection and reporting in each study. We were unable to pool results; we rated the overall strength of evidence (SOE) as high, moderate, low, or insufficient by using guidance suggested by the Agency for Healthcare Research and Quality for its Effective Health Care Program. A total of 20,478 titles were identified; after title, abstract, and full-text review, 166 studies were accepted for abstraction. The vast majority of studies either did not investigate or could not identify risk factors for adverse events (AEs) associated with vaccination. Similarly, the severity of AEs was inconsistently reported, as was information that would make independent severity determination possible. There is evidence that some vaccines are associated with serious adverse events; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide. Careful consideration should be given to the investigation of research gaps, including patient risk factors that may be associated with AEs; however, important factors must be taken into account when determining whether studies are warranted, including the severity and frequency of the AE being studied and the challenges of conducting sufficiently powered studies when investigating rare events.

Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements.

B cells produce a diverse antibody repertoire by undergoing gene rearrangements. Pathogen exposure induces the clonal expansion of B cells expressing antibodies that can bind the infectious agent. To assess human B cell responses to trivalent seasonal influenza and monovalent pandemic H1N1 vaccination, we sequenced gene rearrangements encoding the immunoglobulin heavy chain, a major determinant of epitope recognition. The magnitude of B cell clonal expansions correlates with an individual's secreted antibody response to the vaccine, and the expanded clones are enriched with those expressing influenza-specific monoclonal antibodies. Additionally, B cell responses to pandemic influenza H1N1 vaccination and infection in different people show a prominent family of convergent antibody heavy chain gene rearrangements specific to influenza antigens. These results indicate that microbes can induce specific signatures of immunoglobulin gene rearrangements and that pathogen exposure can potentially be assessed from B cell repertoires.

Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees

BackgroundThe efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine.MethodsSixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN-γ-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry.ResultsAt baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-γ-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination.ConclusionOur results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a significant increase in CD8+ T cell proliferation.

Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: A Phase 1 dose-escalation study in healthy adults

BackgroundNovel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). MethodsA first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15μg, 45μg and 90μg) with and without Alhydrogel®, in healthy adults 18–50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). ResultsThe experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90μg non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). ConclusionsThis is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production.

Seroprevalence of influenza A H1N1 and seroconversion of mothers and infants induced by a single dose of monovalent vaccine

ObjectiveTo determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Materials and MethodsSeropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥1:40. ResultsA total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (<1:40), the prevalence of negative titer in the women received AdimFlu-S (14.8%, 4/31) was lower (p = 0.025) than those received MF59-adjuvanted vaccine (50%, 5/10). ConclusionsSubclinical infection against H1N1 was low in Taiwanese pregnant women in the pandemic 2009. Seropositivity >75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine.

Influenza H1N1 vaccination and adverse pregnancy outcome

Although vaccines against influenza can reduce maternal morbidity and mortality, large-scale data on adverse effects in the offspring are scarce. Historical cohort study in Stockholm County, Sweden. We linked H1N1 vaccination data (Pandemrix(®), a mono-valent AS03 adjuvanted H1N1 vaccine) with pregnancy and birth data from 21,087 women with singleton offspring conceived between February 2009 and January 2010 (vaccinated during pregnancy: n=13,297 vs. unvaccinated: n=7,790). Data were analysed by conceptualizing the observational cohort as a series of nested cohorts defined at each week of gestation. Logistic regression estimated odds ratios (ORs) for low birth weight (LBW,<2,500g), preterm birth (<37 completed weeks), small-for-gestational age (SGA,<10th percentile of the gestational age-specific birth weight within the cohort), low 5-min Apgar score (<7), and caesarean section. Data were adjusted for potential confounders, including maternal age, body mass index, smoking, parity, civil status and comorbidities. Compared with infants of non-vaccinated women, infants of vaccinated women had similar adjusted ORs (95% CI) for LBW (0.91; 0.79-1.04), preterm birth (0.99; 0.89-1.10), SGA (0.97; 0.90-1.05), low Apgar score (1.05, 0.84-1.31), and a marginal risk reduction for caesarean section (0.94, 0.89-0.99). H1N1 vaccination during pregnancy, using an AS03-adjuvanted vaccine, does not appear to adversely influence offspring risks of LBW, preterm birth, SGA, or low Apgar score. Our results suggest that this vaccine is safe for the offspring when used in different stages of pregnancy.

Does vaccine dose predict response to the monovalent pandemic H1N1 influenza a vaccine in children with acute lymphoblastic leukemia? A single‐centre study

Vaccination against influenza is an important strategy in preventing severe infection among children with acute lymphoblastic leukemia (ALL). Successful vaccination depends on both vaccine and host-related factors. We conducted a study on factors predicting the immunogenicity of the monovalent pandemic H1N1 (pH1N1) influenza A vaccine in children with ALL. Children with ALL in our hospital were recruited and received two doses of the inactivated split-virion AS03-adjuvanted vaccine. The serological response was measured before each vaccine dose (Day 0 and 28) and 3 months after the second dose. Antibody titres were measured using a hemagglutination-inhibition assay. Seroconversion was defined as a ≥fourfold increase in antibody titre and a post-vaccination titre ≥1:40. Pre and post-vaccination titres were available from 45 children with ALL after one dose of the vaccine and 39 children after two doses. The seroconversion rate was 11.1% after one dose and 25.6% after the second dose. Univariate analysis demonstrated a significantly higher (P = 0.01) seroconversion rate among children who received the adult dose (0.5 ml) of the vaccine and a trend towards increased seroconversion (P = 0.07) by multivariate analysis. Factors including age, gender, lymphocyte count, treatment phase and regimen did not significantly affect the seroconversion rate. Children who received the adult dose demonstrated a significantly greater magnitude of serological response after both one dose (P = 0.04) and two doses (P = 0.001). These data suggest that the immunogenicity of the pH1N1 vaccine among children with ALL is improved by repeated and adult doses of the vaccine.

Chart-Confirmed Guillain-Barre Syndrome After 2009 H1N1 Influenza Vaccination Among the Medicare Population, 2009-2010

Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.

Verifying Influenza and Pneumococcal Immunization Status of Children in 2009–2010 from Primary Care Practice Records and from the North Carolina Immunization Registry

The North Carolina Immunization Registry (NCIR) has been available since 2004. We sought to measure its utilization among practices that provide primary care for children who are enrolled in a prospective influenza surveillance study. This study included children aged 0.5-17 years who presented with fever or acute respiratory symptoms to an emergency department or inpatient setting in Winston-Salem, North Carolina, from September 1, 2009, through May 19, 2010. Study team members verified influenza and pneumococcal immunization status by requesting records from each child's primary care practice and by independently reviewing the NCIR. We assessed agreement of nonregistry immunization medical records with NCIR data using the kappa statistic. Fifty-six practices confirmed the immunization status of 292 study-enrolled children. For most children (238/292, 82%), practices verified the child's immunizations by providing a copy of the NCIR record. For 54 children whose practices verified their immunizations by providing practice records alone, agreement with the NCIR by the kappa statistic was 0.6-0.7 for seasonal and monovalent H1N1 influenza vaccines and 0.8-0.9 for pneumococcal conjugate and polysaccharide vaccines. A total of 221 (98%) of 226 enrolled children younger than 6 years of age had 2 or more immunizations documented in the NCIR. NCIR usage may vary in other regions of North Carolina. More than 95% of children younger than 6 years of age had 2 or more immunizations documented in the NCIR; thus, the Centers for Disease Control and Prevention 2010 goal for immunization information systems was met in this population. We found substantial agreement between practice records and the NCIR for influenza and pneumococcal immunizations in children.

Association between H1N1 vaccination and narcolepsy–cataplexy

After the beginning of the influenza A (H1N1 pdm09) pandemic in 2009, several monovalent pandemic H1N1 vaccines were licensed using fast track procedures, with limited safety data in children and adolescents.1 Nonadjuvant monovalent vaccines were used in the United States and Australia, and on a limited scale, in Europe (France, Spain) and other countries. Within the European Union (EU), 2 different vaccines with adjuvant were licensed, both containing a new generation of squalene-based adjuvant: Focetria (Novartis, Philadelphia, PA), with the MF59 adjuvant, and Pandemrix (GSK, Philadelphia, PA), containing AS03 (squalene and α-tocopherol). Arepanrix, similar to Pandemrix, was used in Canada and Brazil. The vaccine program started in the EU by September 2009; concurrently, the European Center for Disease Prevention & Control (ECDC), Vaccine Adverse Event Surveillance and Communication, and other agencies initiated an active surveillance program to monitor safety and adverse events associated with this vaccine.

Risk of presentation to hospital with epileptic seizures after vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix): self controlled case series study

Objective To assess the risk of epileptic seizures in people with and without epilepsy after vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix; Glaxo SmithKline, Sweden).Design Register...

Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients

sBackgroundHemodialysis (HD) patients have multiple causes of immune dysfunction and poor immune response to influenza vaccination. We investigated the antibody response rate to a pandemic H1N1/2009 influenza vaccination and clinical parameters influencing the induction of antibody responses in HD patients.MethodsA total of 114 HD patients were vaccinated with a monovalent adjuvanted H1N1 inactivated influenza vaccine. Titers of neutralizing antibodies were evaluated by hemagglutination inhibition (HI) assay at pre- and 4 weeks after vaccination. Seroconversion was defined as either a pre-vaccination HI titer < 1:10 and a post vaccination HI titer > 1:40 or a pre-vaccination HI titer ≥ 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seventeen out of 114 HD patients (14.9%) tested positive for antibodies against influenza A/H1N1/2009 before vaccination. The remaining 97 baseline sero-negative patients were included in the analysis.ResultsOnly 30 (30.9%) HD patients had seroconversion 4 weeks after vaccination. The elderly patients, those over 65 years of age, showed significantly lower seroconversion rate compared to younger HD patients (20.5% vs. 39.6%, p = 0.042). Furthermore, patients with hemoglobin values less than 10 g/dL had a significantly lower seroconversion rate compared to those with higher hemoglobin values (20.0 vs. 38.6%, p = 0.049). By multivariate logistic regression analysis, only age ≥65 years (OR = 0.336, 95% confidence interval (CI) 0.116-0.971, p = 0.044) and hemoglobin levels <10 g/dL (OR = 0.315, 95% CI 0.106-0.932, p = 0.037) were independently associated with seroconversion after vaccination.ConclusionsOur data show that HD patients, especially who are elderly with low hemoglobin levels, are at increased risk for lower seroconversion rate after influenza A/H1N1 vaccination. Further studies are needed to improve the efficacy of vaccination in these high risk patients.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand

Background: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza® Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries.Results:At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8–41.6) and 35.0% (95%CI 15.4–59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05).Methods:We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40.Conclusions:A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.

An Immunization Information System to Meet Evolving Needs During the 2009-2010 Influenza A (H1N1) Vaccination Campaign

In 2009, a monovalent H1N1 influenza (H1N1) vaccine was manufactured in response to the pandemic of 2009 influenza A (H1N1) virus infection that emerged earlier in the year. The overall allocation of the H1N1 vaccine to the states was the purview of the federal government; thereafter, the states were accountable for distributing and reporting the number of doses of H1N1 vaccine administered weekly. This report describes how the Wisconsin Immunization Registry (WIR) was updated and used during the H1N1 immunization campaign and its role in meeting the federal H1N1 immunization reporting requirements. Activities to enhance the registry's functionality included the creation of a rapid data entry screen for providers to facilitate the entry of data into the WIR, and enhancing the reporting capabilities of the WIR to generate H1N1-related reports at the local level. Results of these activities included an increase in the number of WIR users, higher reported numbers of seasonal influenza doses administered, and the establishment of data streams from new users. Data completeness, the ability to accurately forecast doses needed, and validating administered doses were challenges in the changing environment.

High Non‐Specific T Lymphocyte Response to the Adjuvanted H1N1 Vaccine in Comparison with the H1N1/H3N2/B‐Brisbane Vaccine without Adjuvant

Shortly after the report of pandemic 2009 influenza A (H1N1), vaccine manufacturers, in conjunction with public agencies, started developing a H1N1 vaccine. In 2009, various approaches were implemented around the globe. The United States and Australia finally approved only non-adjuvanted H1N1 influenza vaccines, whereas Canada and the EU also approved adjuvanted vaccines. In 2010, seasonal influenza vaccine without adjuvant was again widely accepted in both hemispheres. The addition of adjuvant to the vaccine enhances the immunogenity of the vaccine in the presence of a relatively low amount of antigen. However, it might also induce undesirable non-specific immune response. For this reason, we conducted a prospective observational study to monitor T cell absolute count and H1N1-specific immunogenicity after 2009 and 2010 immunization. Fourteen healthy volunteers received the monovalent H1N1 AS03 adjuvanted influenza vaccine (3.5 μg of H1N1 and squalene-based adjuvant) in October 2009. The immunization was associated with a significant increase in T lymphocyte absolute count (P < 0.0001), reaching abnormal values in 57% of subjects. During this period, none of the subject showed any manifestation of severe viral infection or inflammation. Acute infection by CMV or EBV viruses was also excluded. In October 2010, the same subjects received a seasonal non-adjuvanted influenza vaccine (15 μg of each: H1N1, H3N2, and B-Brisbane). However, after 2010 immunization, no change in T lymphocyte absolute count was observed. H1N1-induced immunogenicity was good for both vaccines. Our results suggest a pronounced non-specific T cell response after AS03-adjuvanted 2009 H1N1 vaccination.

Thymosin α1 continues to show promise as an enhancer for vaccine response

Thymosin α1 (Tα1) is an immune-modulating peptide that can be expected to improve response to vaccinations, as stimulated dendritic cells and T cells can act in concert to increase antibody production along with an improved cytotoxic response from the T cells themselves. Tα1 demonstrated efficacy in preclinical studies; subsequently, it was shown to enhance response to vaccinations in difficult-to-treat populations, including individuals immune suppressed due to age or hemodialysis, and leading to a decrease in later infections. During the 2009 pandemic outbreak of H1N1 influenza, mouse and ferret studies confirmed that the use of higher doses of Tα1 allowed for fewer injections than those used in the previous clinical studies. In addition, a clinical study with Focetria™ MF59-adjuvanted monovalent H1N1 vaccine showed that treatment with Tα1 twice provided an earlier and greater response to the vaccine (P < 0.01).

Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients

Seasonal and pandemic influenza virus infections in renal transplant patients are associated with poor outcomes. During the pandemic of 2009-2010, the AS03-adjuvanted monovalent H1N1 influenza vaccine was recommended for transplant recipients, although its immunogenicity in this population was unknown. We sought to determine the safety and immunogenicity of an adjuvant-containing vaccine against pandemic influenza A H1N1 2009 (pH1N1) administered to kidney transplant recipients. We prospectively enrolled 124 adult kidney transplant recipients in the fall of 2009 at two transplant centers. Cohort 1 (n=42) was assessed before and after pH1N1 immunization, while Cohort 2 (n=82) was only assessed post immunization. Humoral response was measured by the hemagglutination inhibition assay. Vaccine safety was assessed by adverse event reporting, graft function, and human leukocyte antigen (HLA) alloantibody measurements. Cohort 1 had a low rate of baseline seroprotection to pH1N1 (7%) and a low rate of seroprotection after immunization (31%). No patient <6months post transplant (n=5) achieved seroprotection. Seroprotection rate was greater in patients receiving double as compared with triple immunosuppression (80% vs. 24%, P=0.01). In Cohort 2, post-immunization seroprotection was 35%. In both cohorts, no confirmed cases of pH1N1 infection occurred. No difference was seen in estimated glomerular filtration rate before (54.3mL/min/1.73m(2) ) and after (53.8mL/min/1.73m(2) ) immunization, and no acute rejections had occurred after immunization at last follow-up. In Cohort 1, 11.9% of patients developed new anti-HLA antibodies. An adjuvant-containing vaccine to pH1N1 provided poor seroprotection in renal transplant recipients. Receiving triple immunosuppression was associated with a poor seroresponse. Vaccination appeared safe, but some patients developed new anti-HLA antibodies post vaccination. Alternative strategies to improve vaccine responses are necessary.

Functional Status of Older Nursing Home Residents Can Affect the Efficacy of Influenza Vaccination

The efficacy of influenza vaccination in older nursing home residents is frequently overestimated due to frailty selection bias. Limited data exist to examine this issue. We conducted a prospective cohort study from December 2009 to November 2010 to evaluate the efficacy of influenza vaccination in old nursing home residents with respect to their functional status. Participants were stratified according to the Barthel Index (BI) into good functioning (GF; BI > 60), intermediate functioning (IF; BI = 5-60), and poor functioning (PF; BI = 0). Participants were vaccinated by monovalent H1N1 2009 and trivalent seasonal influenza vaccinations (H1N1-TIV), TIV alone, or remained unvaccinated by choice. The associations between all-cause mortality, vaccination efficacy, and functional status were examined. A total of 711 older nursing home residents were enrolled (GF group: N = 230; IF group: N = 246; PF group: N = 235). At 12 months, H1N1-TIV recipients had the lowest all-cause mortality, whereas unvaccinated residents had the highest all-cause mortality in all three functional status groups. In the comparison between H1N1-TIV recipients and TIV alone recipients, the hazard ratios (HRs) of all-cause mortality were lower in the GF group and higher in the PF group (GF group: HR 0.30 [0.07-0.95], p < .05; IF group: HR 0.40 [0.18-0.86], p < .05; PF group: HR 0.53 [0.28-0.99], p < .05). The same observation was found in comparison between other vaccination statuses (H1N1-TIV vs unvaccinated and TIV alone vs unvaccinated). Influenza vaccination was associated with reduced all-cause mortality in older nursing home residents with different functional statuses. Vaccine efficacy in reducing mortality declined with increasingly impaired functional status.

Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine

Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

Factors associated with 2009 monovalent H1N1 vaccine coverage: A cross sectional study of 1308 patients with psoriasis in France

BackgroundPatients with immune-mediated inflammatory diseases like psoriasis are at increased risk of infection. Specific recommendations are available regarding vaccinations however the vaccination coverage in patients with chronic inflammatory diseases has received limited attention and studies are not available in patients with psoriasis. ObjectivesTo assess the coverage of 2009 monovalent H1N1 vaccination and to identify factors associated with vaccination among patients with psoriasis. MethodsPatients member of the French psoriasis patients association were sent a self administrated anonymous questionnaire. It consisted in socio-demographic data, history of psoriasis, seasonal and vaccination status. Factors associated with vaccination for A/H1N1 influenza were identified and adjusted odds ratios (ORa) and prevalence ratios (PRa) were estimated with their 95% confidence intervals (95% CIs) using logistic regression models. Results1308 psoriasis patients with a mean age of 58.2 years completed the study between September and December 2010. A total of 240 (19%) patients received the 2009 monovalent H1N1 vaccine. 25 out of 75 patients treated with biologics (33%) received the vaccine. Previous influenza seasonal (ORa (PRa)=10.2 (6.6) [6.1 (4.1)–16.9 (10.7)]), pneumococcal (ORa (PRa)=2.0 (1.6) [1.2 (1.1)–3.3 (2.3)]) and hepatitis B (ORa (PRa)=2.2 (1.7) [1.4 (1.1)–3.5 (2.5)]) vaccinations were independently associated with being vaccinated for influenza A(H1N1). ConclusionThis is the largest study conducted to assess the coverage of 2009 monovalent H1N1 vaccine among patients with psoriasis, a highly prevalent chronic inflammatory disease. This vaccination coverage is more than twice the one in the French general population, but still remained low for patients receiving immunosuppressants. The limited impact of specific recommendations, free vaccines and the massive national campaign warrant alternative strategies in case of future pandemics.