The immunogenicity of intradermal influenza vaccination in COPD patients

We evaluated the immunogenicity of a reduced-dose intradermal trivalent, inactivated, split-virion seasonal influenza vaccine compared to that of a conventional intramuscular vaccination in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-six COPD patients randomly received either 0.2 ml (6 μg hemagglutinin (HA) per strain) split into two-site intradermal (ID) injections or a single 0.5 ml (15 μg HA per strain) intramuscular (IM) injection. Geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates at 4 weeks post-vaccination in the ID group were less than those in the IM group. Only the seroconversion factor to influenza B in the ID group was statistically less than in the IM group (18.8 in the ID group, n = 81 versus 37.3 in the IM group, n = 75, p = 0.045). Nevertheless, each strain of the ID vaccination met all the Committee for Proprietary Medicinal Products (CPMP) criteria. Seroprotection rates were above 60% throughout the year in influenza A (H3N2), for at least 6 months in influenza A (H1N1) and at least 4 weeks in influenza B in both ID and IM groups. The reduced-dose intradermal vaccination may be considered for use in COPD patients in a vaccine shortage situation.     

Effect of two injections of non-adjuvanted influenza A H1N1pdm2009 vaccine in renal transplant recipients: INSERM C09-32 TRANSFLUVAC trial

Background

Enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. We therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza H1N1pdm2009 in kidney transplant adult recipients.

Methods

A prospective single-arm study was conducted including 121 renal transplant recipients under triple immunosuppressive regimen. Patients received 2 injections (day 0, day 21) of an inactivated, non-adjuvanted H1N1pdm2009 vaccine. Immunogenicity (hemagglutination-inhibition [HI] antibodies and anti-hemagglutin [HA] specific T cells) was evaluated after one and two injections (day 21, day 42) and at 6 months (day 182).

Results

The seroprotection rate (HI antibody titer ≥ 1/40) was 19% at day 0 (n = 119), 53% at day 21 (n = 118), 60% at day 42 (n = 116) (p = 0.013; day 42 vs. day 21) and 56% at day 182 (n = 113). The seroconversion rate was 24% and 32%, the geometric mean fold rise was 3.7 and 4.6 after the first and second injections, respectively. T-cell immunity to the H1N1pdm2009 vaccine showed a two-fold increase from baseline, though not statistically significant, in H1N1pdm2009-HA-specific CD4+ and CD8+ T cells in 34% and 48% of cases, respectively. No rejection episodes related to vaccination were observed while the donor-specific antibodies and creatinine clearance remained unchanged throughout the study.

Conclusion

Administration of two doses of the non-adjuvanted influenza H1N1pdm2009 vaccine in renal transplant patients is safe and induces a significant seroprotection, not strong enough yet to meet European or US requirements for adults below 60 years, but comparable to seroprotection levels usually observed in the non immunosuppressed elderly population or conferred by a single dose of adjuvanted vaccine in solid organ transplant recipients. These results provide useful indications for future strategies required to improve immunogenicity of vaccines against influenza in transplanted patients.     

Immunogenicity of inactivated 2009 H1N1 influenza vaccine in pediatric liver transplant recipients

To assess the safety and immunogenicity of 2009 H1N1 influenza vaccination, 13 pediatric liver transplant recipients and 31 immunocompetent controls received inactivated influenza vaccine without adjuvant according to Japanese guidelines. Serious adverse events and acute allograft rejections were not observed in participants. Seroprotection rates (hemagglutinin-inhibition (HI) antibody titer ≥ 1:40) were 53.8% among recipients and 58.1% among controls (p = 0.797). Seroconversion rates (4-fold or more HI antibody rise) were 46.2% for the recipient group and 51.6% for the control group (p = 0.741). Geometric mean titers were elevated after vaccination in both groups. In comparison with the seasonal influenza vaccination, the seroconversion rate for 2009 H1N1 appeared to be higher than that for seasonal influenza antigens, and the seroprotection rate for 2009 H1N1 clearly increased after vaccination. These findings suggest that pediatric liver transplant patients may respond safely to inactivated 2009 H1N1 influenza vaccines in a manner similar to immunocompetent children.     

Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N = 110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.     

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent,AS03-adjuvanted vaccine in HIV infected adults

Introduction

Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients.

Method

Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n = 60), one (n = 31) or two (n = 128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility.

Results

4–9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%.

Conclusion

A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4–9 months. Two doses improved the immunogenicity further.     

Long-lasting immunogenicity of a virosomal vaccine in older children and young adults with type I diabetes mellitus

To evaluate the long-lasting immunogenicity and reactogenicity of a virosomal influenza vaccine in subjects with type I diabetes, a trial was conducted during the 2007–2008 influenza season in Milan, Northern Italy. One hundred five subjects aged 9–30 years were randomized to receive by intramuscular injection vaccination by a single dose (0.5 ml) of either a virosomal (Inflexal V^®) (n = 52) or a standard subunit (Influvac^®) (n = 53) vaccine. Serum hemagglutinin inhibition antibody titres were determined against the three recommended influenza-like strains, A/H1N1, A/H3N2 and B, at pre-vaccination, and 1 and 6 months post-vaccination. Geometric mean titres were increased in the two groups 1 and 6 months post-vaccination (P < 0.001). One month post-vaccination both vaccines met the CPMP requirement for immunogenicity with high seroprotection rates (>95%) for strains A/H1N1 and A/H3N2, and a seroprotection of 73% and 70% in the virosomal and subunit vaccine for strain B. Mean fold increase ranged 2.8 (A/H3N2)–6.2 (A/H1N1) in the virosomal group and 2.3 (A/H3N2)–4.8 (A/H1N1) in the subunit group. Immunogenicity declined 6 months post-vaccination in both groups, and the CPMP requirement for immunogenicity was satisfied only in the virosomal group. In subjects without pre-existing antibodies to strain B (titre <10), the virosomal vaccine showed higher immune response than the subunit vaccine 6 months post-vaccination, with a geometric mean titre (95% CI) of 40.2 (30.7–54.6) vs. 21.2 (14.6–30.8). Reactogenicity was similar in the two vaccines. All reactions were transient and not severe. The results indicate that in older children and young adults with type I diabetes influenza vaccination with a virosomal or a standard subunit vaccine is safe and adequately immunogenic against the three influenza vaccine strains. In addition, the virosomal vaccine may show better long-lasting immune response than the standard subunit vaccine, especially in subjects without pre-existing antibodies to influenza strains.     

Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: Results from a double-blinded,randomized Phase I clinical trial in healthy Asian volunteers

Methods

A novel, fully bacterially produced recombinant virus-like particle (VLP) based influenza vaccine (gH1-Qbeta) against A/California/07/2009(H1N1) was tested in a double-blind, randomized phase I clinical trial at two clinical sites in Singapore. The trial evaluated the immunogenicity and safety of gH1-Qbeta in the presence or absence of alhydrogel adjuvant. Healthy adult volunteers with no or low pre-existing immunity against A/California/07/2009 (H1N1) were randomized to receive two intramuscular injections 21 days apart, with 100 μg vaccine, containing 42 μg hemagglutinin antigen. Antibody responses were measured before and 21 days after each immunization by hemagglutination inhibition (HAI) assays. The primary endpoint was seroconversion on Day 42, defined as percentage of subjects which reach a HAI titer ≥40 or achieve an at least 4-fold rise in HAI titer (with pre-existing immunity). The co-secondary endpoints were safety and seroconversion on Day 21.

Results

A total of 84 Asian volunteers were enrolled in this study and randomized to receive the adjuvanted (n = 43) or the non-adjuvanted (n = 41) vaccine. Of those, 43 and 37 respectively (95%) completed the study. There were no deaths or serious adverse events reported during this trial. A total of 535 adverse events occurred during treatment with 49.5% local solicited symptoms, of mostly (76.4%) mild severity. The most common treatment-related systemic symptom was fatigue. The non-adjuvanted vaccine met all primary and secondary endpoints and showed seroconversion in 62.2% and 70.3% of participants respectively on Day 21 and Day 42. While the adjuvanted vaccine showed an increased seroconversion from 25.5% (Day 21) to 51.2% (Day 42), it did not meet the immunogenicity endpoint.

Conclusion

In summary, non-adjuvanted gH1-Qbeta showed similar antibody mediated immunogenicity and a comparable safety profile in healthy humans to commercially available vaccines. These results warrant the consideration of this VLP vaccine platform for the vaccination against influenza infection (HSA CTC1300092).     

Long-term immunogenicity of influenza vaccine among the elderly: Risk factors for poor immune response and persistence

The elderly have been considered as the priority group for influenza vaccination, but their influenza vaccine-induced antibody was believed to decline more rapidly. Long-term immunogenicity of the influenza vaccine among the elderly was evaluated as compared to young adults. Serum hemagglutinin inhibition (HI) titers were determined at pre- and post-vaccination periods (at 1, 6, and 12 months after vaccination). Of the 1018 subjects, 716 (70.3%) were followed up during a 12-month period. Seroprotection rates at 1 month post-vaccination ranged from 70.1% to 90.3% depending on the age group and influenza vaccine virus strain. At 6 months post-vaccination, seroprotection rates for all three strains had declined significantly in adults ≥65 years (P < 0.01), but still met the EMEA criteria. Low pre-vaccination HI titer (<1:40) and advanced age were associated with early decline of HI titers, falling below seroprotective levels around 6 months after vaccination.     

Diminished immunogenicity to pandemic H1N1 2009 influenza vaccine in subjects with severe motor and intellectual disability

Subjects with severe motor and intellectual disability (SMID) are considered to be debilitated and at high risk of influenza infection. However, the safety and immunogenicity of pandemic H1N1 (pH1N1) vaccine in these subjects have not been reported. We measured the hemagglutination inhibition antibody titer and calculated the geometric mean titer ratio (GMTR), seroprotection rate, and seroconversion rate in 104 subjects with SMID (mean age ± standard deviation 40.1 ± 12.9 years), and in 179 healthcare workers (40.7 ± 10.4 years) in a long-term care facility. Antibody responses after the first dose of pH1N1 vaccine among workers were greater than the European Medicines Evaluation Agency criteria and US Food and Drug Administration (FDA) criteria: the seroprotection rate was 79.9% (95% confidence interval (CI) 73.3-85.5), the seroconversion rate was 77.9% (95%CI: 70.8-84.0), and GMTR was 7.3 (95%CI: 6.9-7.8). Responses among subjects with SMID were lower than the FDA criteria: the seroprotection rate was 56.3% (95%CI: 46.2-66.1), the seroconversion rate was 54.1% (95%CI: 43.7-64.2), and GMTR was 5.4 (95%CI: 4.9-5.9). Any additional antibody response induced by the second dose of vaccine among subjects with SMID was limited. Multivariate analysis indicated that subjects with SMID had a significantly lower seroprotection rate (odds ratio (OR) 0.37, 95%CI: 0.20-0.66) and seroconversion rate (OR 0.34, 95%CI: 0.20-0.59) than healthcare workers. No serious adverse reaction was reported in either group. These results indicate that a single dose of pH1N1 vaccine does not induce sufficient immunity among subjects with SMID, and a second dose is likely to be ineffective because of diminished immunogenicity. Further study is required to determine if vaccination over consecutive influenza seasons can improve immunogenicity in subjects with SMID.     

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated. Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n = 43) or split vaccine (n = 47). Two blood samples were collected, one before and one 4–6 weeks after vaccination. Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test. Post-vaccine reactions were recorded over 7 days. Seroconversion rates for H1N1, H3N2 and B were 65.1%, 60.4% and 83.7% for virosome vaccine, and 68.0%, 61.7% and 68.0% for split vaccine. Seroprotection rates for H1N1, H3N2 e B were 100%, 97.6% and 69.7% for virosome, and 97.8%, 97.8% and 76.6% for split vaccine. No severe adverse reactions were recorded. Virosome and split vaccines in patients with sickle cell anemia were equally immunogenic, with high seroconversion and seroprotection rates. Both vaccines were well tolerated.     

Comparable humoral response after two doses of adjuvanted influenza A/H1N1pdm2009 vaccine or natural infection in allogeneic stem cell transplant recipients

Background

The present study evaluated immunogenicity and tolerance of two-dose influenza A/H1N1pdm09 vaccination in allogeneic hematopoietic stem cell transplantation (HSCT) recipients, and compared the vaccine-induced humoral response to that triggered by natural infection in another group of HSCT patients.

Methods

Adult allogeneic HSCT recipients vaccinated with two doses of influenza A/H1N1pdm09 vaccine, separated by 3 weeks, and patients with proven influenza A/H1N1pdm09 infection were included. Antibody responses were measured by hemagglutination-inhibition assay 1) on days 0, 21, 42 and 6 months after the first vaccine injection in vaccinated patients and 2) before pandemic and after influenza A/H1N1pdm09 infection, in patients presented natural infection.

Results

At baseline, 3% of 59 recipients of adjuvanted vaccine and 0% of 20 infected patients were seroprotected (antibody titer ≥ 1/40). Seroprotection rate observed 42 days after vaccination was not different from that observed after natural infection (66% and 60% respectively, p = 0.78). In vaccinated patients, seroprotection rate increased significantly from 54% to 66% between day 21 and 42 (p = 0.015). Moreover, after 6 months, seroprotection rate in 21 vaccinated patients was similar to that observed in 10 infected patients evaluated at least 76 days after infection (D76–217) (60% and 81% respectively, p = 0.2). In multivariate analysis, no immunosuppressive treatment or chronic graft-versus-host disease (GVHD) and longer time between transplantation and vaccination/infection were associated with a stronger humoral response. The adjuvanted vaccine was safe with low rate of GVHD worsening.

Conclusion

In HSCT recipients, two doses of influenza A/H1N1pdm09 adjuvanted vaccine were safe and induced a humoral response comparable to that triggered by natural infection in these patients.     

Immune response of single dose vaccination against 2009 pandemic influenza A (H1N1) in the Taiwanese elderly

We conducted a multi-center, randomized and laboratory-blinded clinical trial with subgroup analyses, involving adults aged greater than 60 years old (range 61–86 years old), to investigate the immunogenicity and the potential factors affecting the immune response of a monovalent, unadjuvanted, inactivated, split-virus vaccine. A total of 107 subjects were randomized to receive 15 and 30 μg of hemagglutinin antigen in a 1:1 ratio. The immunogenicity was detected through hemagglutination inhibition (HAI) test of serum obtained before and 3 weeks after vaccination. By 3 weeks after vaccination, HAI titer ≧1:40 was observed in 75.5% and 81.1% of participants receiving 15 and 30 μg of hemagglutinin antigen, respectively. Positive seroconversion was observed in 71.7% and 81.1% of recipients of the 15 and the 30 μg, respectively. The GMTs increased by a factor of 10.7 and 17.4 in the groups of 15 and 30 μg, respectively. This study indicated that one dose of 15 μg hemagglutinin antigen without adjuvant induced protective immune response in the majority of elderly. Multivariate logistic regression analyses showed that gender, age and diabetes were statistically significant factors affecting the seroprotection rate (p = 0.04, 0.01 and 0.01, respectively) and seroconversion rate (p = 0.01, 0.01 and 0.01, respectively).     

Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial

PurposePatients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy.MethodsThis double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates.ResultsA total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups.ConclusionsTrivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population.This study was registered at ClinicalTrials.gov as NCT01666782.     

Enhanced and persistent antibody response against homologous and heterologous strains elicited by a MF59®-adjuvanted influenza vaccine in infants and young children

Background

Non-adjuvanted seasonal influenza vaccines show only modest efficacy in young children. This study compared the immunogenicity, reactogenicity and safety of the MF59^®-adjuvanted trivalent subunit vaccine (aTIV) with two non-adjuvanted trivalent vaccines, TIV-1, the non-adjuvanted version of aTIV, and TIV-2, a split virion vaccine.

Methods

6078 children received two doses of aTIV (n = 3125), TIV-1 (n = 1479), or TIV-2 (n = 1474) four weeks apart (Days 1 and 29). Children aged 6 to <36 months and 36 to <72 months received 0.25 mL and 0.50 mL doses, respectively. Immunogenicity was assessed by hemagglutination inhibition (HI) assay (n = 2435) on Days 1, 29, 50 and 209. Safety was assessed up to Day 394.

Results

After the second vaccination (Day 50), the aTIV group showed significantly higher geometric mean HI titers and seroconversion rates than the TIV-1 or TIV-2 groups against all homologous and heterologous strains. The difference was enhanced at HI titers ≥110. aTIV elicited a faster, more persistent antibody response, with significantly higher titers in the aTIV group after one vaccination (Day 29) and after six months (Day 209) than in either TIV group. aTIV was more reactogenic than were TIV-1 and TIV-2 but rates of severe adverse events were very low for all three vaccines.

Conclusion

In infants and young children, the MF59-adjuvanted vaccine induced substantially faster (after one dose), higher, persistent HI titers than the non-adjuvanted vaccines, with consistently higher seroprotection rates at increased threshold HI titers.This trial is registered at clinicaltrials.gov: NCT01346592.     

Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza vaccine in children with juvenile idiopathic arthritis

In order to evaluate the immunogenicity, safety, and tolerability of the MF-59 adjuvanted seasonal influenza vaccine in children and adolescents with juvenile idiopathic arthritis (JIA) treated with different anti-rheumatic drugs, 60 pediatric patients with JIA (30 treated with disease-modifying anti-rheumatic drugs [DMARDs] and 30 with etanercept) were compared with 30 healthy controls of similar gender and age. All of the patients received a single dose of the MF59-adjuvanted seasonal influenza vaccine (Fluad, Siena, Italy). Immunogenicity was assessed at baseline, and 1 and 3 months post-vaccination; safety and tolerability were also evaluated during the study period. The JIA patients treated with etanercept showed significantly lower geometric mean titres (GMTs) against the A/H1N1 strain than those treated with DMARDs (p < 0.05) and the healthy controls (p < 0.05), who had similar GMTs. The etanercept-treated JIA patients also showed a significant reduction in GMTs against the A/H1N1 and A/H3N2 strains from 1 to 3 months after vaccination (p < 0.05). Furthermore, their seroconversion and seroprotection rates, and B antigen GMTs, were all significantly lower than those of the subjects in the other two groups (p < 0.05). The safety and tolerability of the vaccine were good and similar between the groups. The results of this study indicate a reduced immune response to MF59-adjuvanted seasonal influenza vaccine in JIA children and adolescents treated with etanercept in comparison with those treated with DMARDs and healthy controls. The safety and tolerability of the vaccine appeared to be good in all of the study population.     

Vitamin D is not associated with serologic response to influenza vaccine in adults over 50 years old

Vitamin D deficiency has been implicated in risk of respiratory illness. We determined whether serum vitamin D levels are related to influenza vaccine response measured by hemagglutination antibody inhibition (HAI) titer in adults aged ≥50 years old. The study was a prospective cohort study conducted over two influenza seasons (fall 2008–spring 2009 and fall 2009–spring 2010) in Marshfield, WI and Nashville, TN including 1103 community-dwelling adult volunteers ≥50 years of age. Pre-vaccination levels of serum vitamin D and HAI titer levels pre- and 21–28 days post-influenza vaccination were measured. Seroprotection was defined as HAI ≥40; seroconversion was defined as ≥4-fold rise in HAI titers from pre- to post-vaccination. More than 25% of participants were vitamin D deficient (<25 ng/mL). Vitamin D measured as a continuous variable was not related to pre- or post-vaccination seroprotection or seroconversion for any vaccine strain in any year. Vitamin D deficiency was associated with a greater frequency of post-vaccination seroprotection for seasonal H1N1 in the first year of the study, but was not related to seroprotection or seroconversion for any other strain in either year. No consistent association was found between vitamin D levels or vitamin D deficiency and serologic response to influenza vaccination in older adults. Cell-mediated immune parameters should also be explored in order to further investigate possible relationships between micronutrient status and influenza vaccine response.     

Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: Data from two multicentre randomised trials

During the 2009–2010 Northern Hemisphere influenza season, both seasonal and pandemic influenza vaccines were expected to be administered to elderly people, which is an important target group for influenza vaccination. Two multicentre randomised clinical studies were conducted in participants aged ≥61 years to assess the immunogenicity and reactogenicity following vaccination with two doses of an AS03-adjuvanted A(H1N1)pmd09 vaccine when either sequentially administered (21 days before first dose [N = 73] or 21 days after second dose [N = 72]) or co-administered (first dose [N = 84] or second dose [N = 84]) with a licensed trivalent seasonal influenza vaccine (TIV). Overall, 313 participants from 2 centres in Sweden (ClinicalTrials.gov, NCT00968890) and 6 centres in Germany (NCT00971425) were randomised to one of the four treatment groups. The AS03-adjuvanted A(H1N1)pmd09 vaccine elicited a good immune response against A(H1N1)pmd09-like virus in all treatment groups after the first and second dose, meeting and exceeding the European licensing criteria for pandemic influenza vaccines. After one dose of the AS03-adjuvanted A(H1N1)pmd09 vaccine, haemagglutination inhibition seroconversion rates ranged from 85% (95% confidence interval: 74–93%) to 93% (85–97%), seroprotection rates from 87% (76–94%) to 96% (90–99%) and geometric mean fold rise from 15 (11–19) to 20 (16–25). The haemagglutination inhibition immune responses to the AS03-adjuvanted A(H1N1)pmd09 vaccine seemed lower when TIV was administered 3 weeks before, while immune responses to TIV seemed not affected by either vaccination schedule. Solicited symptoms were more frequently reported following administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine compared to TIV, but these were mainly mild to moderate in intensity and transient in the four treatment groups. These results suggest that sequential or co-administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine and TIV induced a good immune response to both vaccines and had a clinically acceptable safety profile in people aged ≥61 years.     

Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and polymyositis: Immunogenicity independent of therapy and no harmful effect in disease

The goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1 ± 9.9 vs. 43.8 ± 8.4 years, p = 0.607) and gender distribution (p = 1.00) were comparable between the patients and controls. After 21 days, seroconversion (p = 0.394), seroprotection (p = 0.08), GMT (p = 0.573) and the FI in the GMT (p = 0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p = 0.20) and aldolase levels (p = 0.98), the physicians’ VAS (p = 1.00), the patients’ VAS (p = 1.00) and the MMT-8 (p = 1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p = 0.969), GC >0.5 mg/kg/day (p = 0.395) and GC + immunosuppressors (p = 0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p > 0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.     

Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjögren's syndrome

Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p = 0.42), seroprotection (83.3 vs. 72.2%, p = 0.26) and FI-GMT (p = 0.85). Disease duration, prednisone (2.1 ± 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p > 0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p > 0.05) and only mild side effects were reported in comparable rates to controls (p > 0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p = 0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p = 0.0001) and anti-La/SSB (p = 0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.     

Pandemic whole-virion,Vero-cell-derived,adjuvant-free influenza A H1N1 vaccine in patients with solid tumors and hematologic malignancies receiving concurrent anticancer treatment: Immunogenicity,tolerability, and acceptability during the pandemic situation

Patients with malignancies are considered to be at increased risk of acquiring influenza. Because of higher complication and case fatality rates, preventive measures such as vaccination are of great interest. The objective of this study was to assess the acceptability, tolerability and immunogenicity of an adjuvant-free whole-virion pandemic influenza A (H1N1) vaccine in cancer patients with ongoing anticancer treatment during a ‘pandemic situation’. Adult patients with hematologic malignancies or solid tumors and concurrent cytotoxic, targeted, and/or hormone therapy were recruited during the influenza A (H1N1) pandemic in 2009/2010 and were offered free vaccine. Antibody titers were measured using virus-specific hemagglutination inhibition assay and ELISA. Among 285 patients with solid tumors who were offered vaccination during their therapy, 260 (91.2%) declined and 25 (8.8%) accepted. Seventeen patients with hematologic malignancies were also vaccinated during therapy; 23 healthy individuals served as a control group. When measured using hemagglutination-inhibition assays, rates of seroprotection, seroconversion, and geometric mean titer ratios after the second vaccination were 96%, 70%, and 4.1 respectively among the healthy individuals, 90%, 52%, and 4.3 among patients with solid tumors, and 67%, 13%, and 1.5 among patients with hematologic malignancies during therapy (P < 0.05). When measured using ELISA, seropositivity differed significantly among the three groups after the second vaccination: healthy individuals 74%, patients with solid tumors 57%, those with hematologic malignancies 13% (P < 0.001). The vaccine was well tolerated. Our results demonstrate a low uptake of the well tolerated adjuvant-free influenza A (H1N1) vaccine by cancer patients receiving anticancer treatment during the pandemic of 2009/2010. Among the vaccinated patients, the immune response was weaker than that in healthy individuals. The immune response in patients with hematological malignancies was low. Two doses of vaccine are needed in these immunosuppressed patients.