Importance of vaccination habit and vaccine choice on influenza vaccination among healthy working adults

This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18–49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P < .02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P < .01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P < .001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice.     

Safety and immunogenicity of a 2009 influenza A (H1N1) vaccine in hemodialysis patients

A worldwide vaccination campaign against the 2009 pandemic influenza A (H1N1) virus was launched among high-risk subjects, including hemodialysis patients. The long-term immunogenicity of an influenza vaccine has not been investigated in hemodialysis patients. This study aimed to (1) assess the long-term immunogenicity of a monovalent non-adjuvanted influenza A (H1N1) vaccine in hemodialysis patients and (2) determine the safety of this vaccine. We conducted a prospective cohort study of 44 hemodialysis patients and 149 healthy controls in 2010. All of the participants received a single dose of the monovalent non-adjuvanted 2009 influenza A (H1N1) vaccine. The level of antibodies was measured at baseline and at 4 and 24 weeks post-vaccination using a hemagglutination inhibition assay. The outcomes were the percentages of participants who achieved seroconversion and seroprotection (titer ≥1:40) 4 and 24 weeks after vaccination. At 4 weeks post-vaccination, seroconversion was observed in 17 (38.6%) of the hemodialysis patients and 94 (63.1%) of the controls (P = 0.056), and protective titers were obtained in 22 (50%) of the hemodialysis patients and 100 (67.1%) of the controls (P = 0.426). At 24 weeks post-vaccination, immunogenicity decreased in both the hemodialysis patients and the controls, but there were no significant differences between the hemodialysis patients and the controls in the seroconversion rate (27.3% versus 36.9%, P = 0.526) or the seroprotection rate (38.6% versus 48.3%, P = 0.996). No differences in adverse events were observed between the hemodialysis patients and the controls. In summary, the 2009 influenza A (H1N1) vaccine elicits a similar immune response in both hemodialysis patients and healthy controls, but immunity declines 24 weeks after vaccination in both groups. Hemodialysis patients should at least be vaccinated annually against the influenza virus.     

What a pandemic teaches us about vaccination attitudes of parents of children with asthma

Background

During the recent pandemic, Influenza A/H1N1 vaccine uptake remained far below the targeted rates. Associated factors regarding vaccine refusal in the general population have been reported in many studies, however the reasons behind refusals for asthmatic children have not yet been identified. We aimed to investigate Influenza A/H1N1 virus vaccine acceptance for children with asthma, to determine the attitudes and beliefs of parents concerning Influenza A/H1N1 disease and vaccine and to identify the association of asthma control parameters with vaccination.

Methods

The parents of asthmatic children aged 6–18 years participated in a cross-sectional survey study in three pediatric allergy outpatient clinics. The survey measured demographic factors, asthma control parameters, vaccination rates, and beliefs and attitudes regarding Influenza A/H1N1 vaccine.

Results

Of the 625 asthmatic children, 16.8% (n = 105) were immunized with Influenza A/H1N1 and 45.7% (n = 286) with seasonal influenza vaccine. Educational background of parents (p < 0.001 and p = 0.002, for father's and mother's educational level, respectively), previous vaccination with seasonal influenza (p < 0.001), and having a family member vaccinated against Influenza A/H1N1 (p < 0.001) had a significant influence on vaccine acceptance, while fear of side effects (88.6%) was the major parental reason for refusing the vaccine. Asthma control parameters had no influence on uptake of the vaccine. Physician recommendation (84.8%) was important in the decision-making process for immunization. The statement “Children with asthma should receive swine flu vaccine” increased the likelihood of being vaccinated [OR: 2.160, (95%CI 1.135–4.111), p = 0.019].

Conclusion

Although asthmatic children are considered to be a high-priority group for Influenza A/H1N1 vaccination, we found low uptake of vaccine among our patients. Beliefs and attitudes rather than asthma control parameters influenced parental decisions for immunization. Understanding the underlying determinants for refusing the vaccine will help to improve vaccine campaigns in advance of a future outbreak.     

Cross-protection against influenza virus infection by intranasal administration of M1-based vaccine with chitosan as an adjuvant

The antigenic variation of influenza virus represents a major health problem, thus continuous efforts have been made to develop broad-spectrum vaccines against influenza virus. Matrix protein 1 (M1) protein is highly conserved in all influenza A strains. In this study, M1 protein was efficiently expressed in Escherichia coli (E. coli), then purified and used for immunization of BALB/c mice by intranasal drip using chitosan as adjuvant. The M1 protein was administered intranasally to mice in combination with chitosan adjuvant twice at an interval of 3 weeks. Three weeks after the second immunization, the mice were challenged with a lethal dose (5 × LD₅₀) of A/Chicken/Jiangsu/7/2002 (H9N2) virus, PR8 (H1N1) virus and A/Chicken/Henan/12/2004 (H5N1) virus. The protective immunity of the vaccine was evaluated by determining the survival rates, residual lung virus titers, bodyweight, and the serum antibody titers of the mice. The results showed that nasal administration of 100 μg M1 in combination with chitosan could not only completely protect the mice effectively against the challenge of the homologous virus but also protect 70% and 30% of the mice against the heterologous H1N1 and H5N1 viruses, respectively. The study indicated that the M1 protein was a candidate antigen for a broad-spectrum influenza virus vaccine and the adjuvant chitosan significantly improved the efficacy of the M1 vaccine.     

Surface antibody and cytokine response to recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine

Objective

To compare the immune responses of the 10 μg and 20 μg doses of CHO hepatitis B vaccine on adults.

Methods

Adults aged 18-45 years who gave a history of never having received hepatitis B vaccine and lacked serologic evidence of infection to hepatitis B virus (HBV) infection or previous vaccination were enrolled into the study. A total of 642 eligible participants were randomized to receive 3 doses of either the 10 μg or the 20 μg formulation of CHO hepatitis B vaccine in a 0-1-6 month schedule. Each study subject had a serologic specimen collected one month following the third vaccine dose that was tested for markers of HBV infection and anti-HBs by Abbott I2000. Persons who tested negative for anti-HBs negative persons were tested for HBV DNA. Logistic regression was used to identify factors associated with antibody response. Among the participants, 153 subjects had their lymphocytes cultivated and tested for cytokine production. Enzyme-linked immunospot (ELISPOT) was used to test spot numbers of IL-4, IFN-γ which produced by lymphocyte.

Results

The anti-HBs seroconversion rate was 88.8% (95% CI: 85.4-92.2%) and 95.3% (95% CI: 93.0-97.6%), respectively in 10 μg and 20 μg group. Geometric mean titers (GMT) were 173.42 mIU/ml and 585.51 mIU/ml, respectively in 10 μg and 20 μg groups. Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus infector, older age and receipt of the 10 μg dose were all negatively associated with antibody response (P < .05). Cellular immunity results showed: IL-4 immunity spot numbers in 20 μg group was higher than 10 μg group. With anti-HBs increased, the IL-4 immunity spot numbers increased significantly which had significant positive correlation (Spearman coefficient = 0.538, P < 0.0001). IFN-γ spot numbers had no statistical significant between the two groups.

Conclusion

The humoral immunity and cytokines response among the group that received the 20 μg CHO hepatitis B vaccine dose was superior compared to the group that received the 10 μg dose. The 20 μg dose of CHO hepatitis B vaccine should be prioritized for adult vaccination programs in China.     

SLAM and DC-SIGN measles receptor polymorphisms and their impact on antibody and cytokine responses to measles vaccine

Background

Despite the use of measles vaccine, measles virus continues to circulate and cause severe disease. Immune responses to the measles vaccine are variable between individuals, with up to 10% failing to produce a sufficient protective response post-vaccination. Signaling lymphocyte activation molecule (SLAM) and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) are specific measles receptors: SLAM binds and permits entry of the virus into the cell, DC-SIGN acts as an attachment receptor, increasing viral binding efficiency and transmission. Genetic variations in these receptor genes may alter measles vaccine antibody and cellular responses.

Methods

In 12-month-old infants from Perth, Western Australia after their first measles vaccine dose as part of the combination measles-mumps-rubella (MMR) vaccine, 7 SLAM and DC-SIGN polymorphisms were genotyped and associations were investigated with measles IgG antibody levels and in vitro measles cytokine responses.

Results

The DC-SIGN promoter variant −336C/T was associated with overall IFN-γ responses after measles stimulation (P = 0.002) and three DC-SIGN polymorphisms (−336C/T, −139C/T and −871C/T) were associated with the proportion of cytokine non-responders to measles (P = 0.001, P = 0.021 and P = 0.036, respectively). However, no associations were found between the DC-SIGN or SLAM polymorphisms and measles IgG antibody levels.

Conclusions

The results suggest that DC-SIGN −139C/T, −336C/T and −871C/T polymorphisms may modulate cytokine (but not antibody) responses to the measles component of MMR vaccine. Furthermore, contrasting previous studies, SLAM polymorphisms do not appear to affect measles antibody or cytokine responses in this cohort.     

Evaluation of Southern Hemisphere influenza vaccine recommendations

In 1999, the World Health Organization switched from annual to semi-annual recommendations for influenza vaccine composition. We compared the antigenic match between recommendations and circulating viruses before and after 1999, in the Northern and Southern Hemispheres. Vaccine match proportion for A/H3N2 viruses increased from 31% to 59% in the Southern Hemisphere (P < 0.05), and is now comparable to that in the Northern Hemisphere. Vaccine match for influenza B decreased from ∼100% to 33–54% in both hemispheres (P < 0.05), following the unexpected resurgence of influenza B/Victoria in 1997. No estimate was available for influenza A/H1N1. We conclude that semi-annual vaccine recommendations are useful overall and discuss potential ways forward, including a recommendation for the improvement of vaccination policy and influenza surveillance in tropical areas.     

DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Background

We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.

Methods

Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.

Results

Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = −1.5, 67.7) for ‘Any illness with or without fever’ and 53% for ‘Upper respiratory tract infection’ (95% CI = 8.0, 77.7).

Conclusion

It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.     

Shedding of Ann Arbor strain live attenuated influenza vaccine virus in children 6-59 months of age

Background

A trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved for use in children 24 months of age and older in a number of countries. The incidence, duration, and other parameters of viral shedding after vaccination with LAIV have not been fully described in children ≤5 years of age.

Methods

An open-label, single-arm, multicenter, phase 2 study assessed viral shedding and safety in 200 children 6-59 months of age after a single, intranasal dose of LAIV in 2006. Participants were enrolled into 2 age groups: 6-23 months (n = 100) and 24-59 months (n = 100) of age. Viral shedding, reactogenicity, and adverse events were assessed for 28 days postvaccination. Serious adverse events and significant new medical conditions were monitored for 180 days postvaccination.

Results

Viral shedding was detected by culture in 79% (95% CI, 73-84) of vaccine recipients and occurred more frequently in children 6-23 months of age (89%) compared with children 24-59 months of age (69%). In total, 157 subjects shed vaccine, which was confirmed by RT-PCR as A/H1N1 for 128 subjects, A/H3N2 for 72 subjects, and B for 74 subjects. The incidence of shedding was highest on day 2 (59% in the 6-23 month age group; 41% in the 24-59 month age group) and most shedding occurred 1-11 days postvaccination; shedding after 11 days was infrequent and occurred almost exclusively in children 6-23 months of age. Mean titers of shed vaccine virus peaked on day 2 and were generally <10^3.0 median tissue culture infective dose/mL for both groups. Reactogenicity events peaked on day 2; runny/stuffy nose was reported most frequently (63% of all subjects).

Conclusion

Most children 6-59 months of age vaccinated with Ann Arbor strain LAIV shed ≥1 vaccine virus within 11 days of vaccination. Shedding was less common in children 24-59 months of age, a population for whom LAIV is approved for use. Titers of shed vaccine were low, which may explain why secondary transmission of LAIV was observed very infrequently in a previous controlled study conducted with young children in a daycare setting.     

CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation

Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral^® containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10–18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P < 0.01) and IFN-γ production (P < 0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P > 0.05). The IFN-γ production was significantly higher (P < 0.01) but the blast formation comparable (P > 0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P < 0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-γ as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.     

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.     

Sub-optimal prevalence of mumps antibodies in a population based study of young adults in Israel after 20 years of two dose universal vaccination policy

Background

A recent mumps outbreak in Israel despite an ongoing national program of a 2-dose universal childhood vaccination policy since 1988, raised questions regarding population immunity among young adults.

Objective

To assess the seroprevalence of mumps antibodies among young Israeli adults born after 1987 in order to determine evidence based vaccination policy.

Methods

We conducted a seroprevalence study of mumps IgG antibodies among 441 Israeli adults born in 1988-9, based on a representative sample of sera collected upon recruitment to mandatory military service in 2007.

Results

The overall seroprevalence of IgG antibody to mumps virus among 1988-9 born was 83.7%, 82.1% among males and 85.7% among females. Seroprevalence among 2007 recruits was similar to 1999 recruits (83.3%, P = 0.89) and significantly lower than 1987 recruits (94.1%, P < 0.0001). The absolute decrease between 2007 and 1987 for males was 13.1% (P < 0.0001) and for females 7.0% (P = 0.02). Seroprevalence was not significantly higher among native Israelis (84.9%) than among young adults born in the Commonwealth of Independent States (81.1%, P = 0.46) and significantly higher compared to young adults born in Western Europe or North America (68.2%, P = 0.045).

Conclusions

Our findings indicate sub-optimal population seroprevalence despite a 2-dose universal childhood vaccination policy. This study allows better understanding of current mumps outbreaks in Israel and elsewhere following periods of low circulation of wild virus. These findings support mumps vaccination, even for populations and individuals that received two doses during childhood, as means for outbreak containment among young adults, especially in crowded settings, and serve as a reminder to the need for dynamic vaccination policy, supported by health promotion activities.     

Predictors of acceptance of H1N1 influenza vaccination by FDNY firefighters and EMS workers

Background

There is a widely recognized need for vaccination of health care workers (HCWs). We undertook this study to assess the 2009-2010 H1N1 vaccination rates in ∼14,000 firefighters and emergency medical service (EMS) workers at the Fire Department of New York (FDNY) and to determine predictors of H1N1 vaccine acceptance.

Methods

After 9/11/01, FDNY developed a bio-preparedness drill where units are dispatched to FDNY-BIOPOD (biologic points of distributions) for rapid distribution of medications/vaccines in the event of a biological disaster. Since 2005, FDNY offers free, voluntary seasonal influenza vaccination during routine medical monitoring/treatment examinations and at FDNY-BIOPOD. In 2009, FDNY-BIOPOD instead offered the H1N1 vaccine. We report on FDNY H1N1 vaccination rates and on predictors of acceptance using bivariate and multivariable techniques.

Results

Overall, 10,612 (77%) FDNY workers were offered H1N1 vaccination, of whom 5831 (55%) accepted. Acceptance was 57.2% during FDNY-BIOPOD compared with 34.4% during medical monitoring/treatment exams (p = 0.0001). Workers who accepted prior seasonal influenza vaccinations were 4 times more likely to accept H1N1 vaccination (AOR = 4.4, CI₉₅ = 4.0-4.8).

Conclusion

FDNY offered H1N1 vaccination to 77% of its workforce during the 2009-2010 season. Prior seasonal vaccine acceptance and vaccination in a group setting such as FDNY-BIOPOD dramatically increased acceptance of the H1N1 vaccine. However, within a voluntary program, additional strategies are needed to further increase vaccine acceptance in first responders and other HCWs.     

Priming with a DNA vaccine delivered by attenuated Salmonella typhimurium and boosting with a killed vaccine confers protection of chickens against infection with the H9 subtype of avian influenza virus

Control of the circulation of H9 low-pathogenic avian influenza virus (LPAIV) is a major concern for both animal and public health. To improve vaccine efficacy against H9 LPAIV, we have utilized a novel prime–boost vaccination strategy. Specific-pathogen free (SPF) chickens were first orally immunized with a hemagglutinin (HA) DNA vaccine delivered by attenuated Salmonella typhimurium, followed by boosting with a killed avian influenza (AI) vaccine. Chickens in this combined vaccination group were completely protected against both oropharyngeal and cloacal virus shedding after intranasal challenge with H9N2 AIV, while viruses were detected from these sites in other vaccination groups. Prior to challenge, chickens in the prime–boost group also had higher (P < 0.05) serum hemagglutination inhibition (HI) titers and intestinal mucosal IgA ELISA titers against AIV, and higher lymphoproliferation stimulation indices than those from other groups. Thus, we have demonstrated the efficacy of a novel prime–boost vaccination strategy against H9N2 avian influenza virus, which could be also applied for the development of vaccines against other mucosally infectious pathogens.     

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.     

Predicting vaccination using numerical and affective risk perceptions: The case of A/H1N1 influenza

During the 2009 A/H1N1 flu pandemic, German health authorities recommended vaccination; however, the efficacy of such programs largely depends on individuals’ risk perception. Risk perceptions are commonly determined through numerical-cognitive estimates such as the perceived likelihood and severity of the hazard. Instead, we argue that risk perceptions, which include more affect-related aspects such as worry and threat, are more powerful predictors of protective behaviors. Moreover, vaccines are often perceived as double-edged since they offer protection but also involve adverse side-effects. As such, in the context of the A/H1N1 vaccine uptake, risk perception is not only disease-related (A/H1N1 infection) but also vaccine-related (A/H1N1 vaccine). The present longitudinal study was conducted during the run-up to the German A/H1N1 vaccination campaign and measured cognitive and affective risk perceptions associated with both the A/H1N1 infection and its vaccine (T1, October 2009, N = 397) in order to assess their impact on (self-reported) A/H1N1 vaccination eight weeks later (T2, December 2009; N = 285). As assumed, greater perceived likelihood and severity of infection were associated with greater affective risk perception at T1. The more threatened and worried people felt, the more they intended to get vaccinated; however, the greater the perceived likelihood and severity of vaccine adverse side-effects, the greater the amount of vaccine related affective risk perception, impeding vaccination intention. Finally, vaccination intention predicted vaccination eight weeks later at T2 (OR = 2.2). The results suggest that numerical-cognitive risk perceptions, which are typically the target of public vaccination campaigns, do not impact preventive intention directly; instead, they facilitate affect-related risk perceptions, which motivate protective action.     

Cluster randomized trial of a toolkit and early vaccine delivery to improve childhood influenza vaccination rates in primary care

Purpose

To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial.

Methods

Twenty primary care practices treating children (range for n = 536–8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months–18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010–2011 and 2011–2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes.

Results

Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P < 0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms – 8/10 Intervention (all P < 0.001) and 7/10 Control sites (P-values = 0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.23–1.34), having commercial insurance (OR = 1.30; 95%CI = 1.25–1.35), higher pre-intervention practice vaccination rate (OR = 1.25; 95%CI = 1.16–1.34), and being in the Intervention arm (OR = 1.23; 95%CI = 1.01–1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates.

Conclusions

Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates.Clinical trial registry name/number: From Innovation to Solutions: Childhood Influenza/NCT01664793.     

Pertussis vaccination coverage among adults in the Lyon area

Background

The compliance with recommendations for Pertussis vaccination was assessed in the Lyon population through vaccination coverage (VC).

Methods

A cross-sectional study was conducted in collaboration with 10 private biological analysis laboratories between October 2010 and March 2012, on 1930 adults (>19 years of age) from the Lyon area. Proof of vaccination (PV) was requested to prove the current vaccination status.

Results

A percentage of 30.3% (585/1930) of surveyed individuals provided a PV. A positive vaccination status was confirmed in 10.76% [CI 95% 8.45–13.48] (63/585) and didn’t vary in relation to gender (P = 0.57), age (P = 0.06), or level of schooling (P = 0.41). Coverage vaccination was not updated in parents with childbearing project (84.2% (64/76) [CI 95% 74.7–91.2]) or people in contact with children less than 6 years of age (83.6% (87/104) [CI 95% 75.6–89.8]). Pertussis vaccination wasn’t confirmed in 80.0% (124/155) of those who thought being vaccine up to date.

Conclusions

The Lyon population poorly complied with the cocooning strategy implemented in 2004. The pertussis vaccine coverage confirmed by a PV proved the inadequate rate of vaccination compared to objectives. It is mandatory to strengthen the vaccinal policy for this vaccine booster.     

Evidence for differing evolutionary dynamics of A/H5N1 viruses among countries applying or not applying avian influenza vaccination in poultry

Highly pathogenic avian influenza (HPAI) H5N1 (clade 2.2) was introduced into Egypt in early 2006. Despite the control measures taken, including mass vaccination of poultry, the virus rapidly spread among commercial and backyard flocks. Since the initial outbreaks, the virus in Egypt has evolved into a third order clade (clade 2.2.1) and diverged into antigenically and genetically distinct subclades. To better understand the dynamics of HPAI H5N1 evolution in countries that differ in vaccination policy, we undertook an in-depth analysis of those virus strains circulating in Egypt between 2006 and 2010, and compared countries where vaccination was adopted (Egypt and Indonesia) to those where it was not (Nigeria, Turkey and Thailand). This study incorporated 751 sequences (Egypt n = 309, Indonesia n = 149, Nigeria n = 106, Turkey n = 87, Thailand n = 100) of the complete haemagglutinin (HA) open reading frame, the major antigenic determinant of influenza A virus. Our analysis revealed that two main Egyptian subclades (termed A and B) have co-circulated in domestic poultry since late 2007 and exhibit different profiles of positively selected codons and rates of nucleotide substitution. The mean evolutionary rate of subclade A H5N1 viruses was 4.07 × 10⁻³ nucleotide substitutions per site, per year (HPD 95%, 3.23-4.91), whereas subclade B possessed a markedly higher substitution rate (8.87 × 10⁻³; 95% HPD 7.0-10.72 × 10⁻³) and a stronger signature of positive selection. Although the direct association between H5N1 vaccination and virus evolution is difficult to establish, we found evidence for a difference in the evolutionary dynamics of H5N1 viruses among countries where vaccination was or was not adopted. In particular, both evolutionary rates and the number of positively selected sites were higher in virus populations circulating in countries applying avian influenza vaccination for H5N1, compared to viruses circulating in countries which had never used vaccination. We therefore urge a greater consideration of the potential consequences of inadequate vaccination on viral evolution.     

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.