Efficacy of the herpes zoster zubunit vaccine in adults 70 years of age or older

Background: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70).

Methods: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50.

Results: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups.

Conclusions: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older.

Early protection in sheep against intratypic heterologous challenge with serotype O foot-and-mouth disease virus using high-potency, emergency vaccine

In 2009-2011, spread of a serotype O foot-and-mouth disease virus (FMDV) belonging to the South East Asia topotype led to the culling of over 3.5 million cattle and pigs in Japan and Korea. The O1 Manisa vaccine (belonging to the Middle East-South Asian topotype) was used at high potency in Korea to limit the expansion of the outbreak. However, no data are available on the spread of this virus or the efficacy of the O1 Manisa vaccine against this virus in sheep. In this study, the early protection afforded with a high potency (>6 PD50) FMD O1 Manisa vaccine against challenge with the O/SKR/2010 virus was tested in sheep. Sheep (n=8) were vaccinated 4 days prior to continuous direct-contact challenge with donor sheep. Donor sheep were infected with FMDV O/SKR/2010 by coronary band inoculation 24h prior to contact with the vaccinated animals, or unvaccinated controls (n=4). Three of the four control sheep became infected, two clinically. All eight O1 Manisa vaccinated sheep were protected from clinical disease. None had detectable antibodies to FMDV non-structural proteins (3ABC), no virus was isolated from nasal swabs, saliva or oro-pharyngeal fluid and none became carriers. Using this model of challenge, sheep were protected against infection as early as 4 days post vaccination.

The brachyspira hyodysenteriae ftnA gene : DNA vaccination and real-time PCR quantification of bacteria in a mouse model of disease

The nucleotide sequence of the Brachyspira hyodysenteriae ftnA gene, encoding a putative ferritin protein (FtnA), was determined. Analysis of the sequence predicted that this gene encoded a protein of 180 amino acids. RT-PCR and Western blot showed that the ftnA gene was expressed in B. hyodysenteriae, and evidence suggests that FtnA stores iron rather than haem. ftnA was delivered as DNA and recombinant protein vaccines in a mouse model of B. hyodysenteriae infection. Vaccine efficacy was monitored by caecal pathology and quantification of B. hyodysenteriae numbers in the caeca of infected mice by real-time PCR.

Cost-effectiveness of a bivalent human papillomavirus vaccination program in Japan

Background Human papillomavirus (HPV) vaccines and their widespread adoption have the potential to relieve a large part of the burden of cervical cancer morbidity and mortality, particularly in countries that have low screening rates or, like Japan, lack a cohesive universal screening program. An economic evaluation was conducted to assess the cost-effectiveness of introducing a bivalent HPV vaccination program in Japan from a healthcare perspective. METHODS: A Markov model of the natural history of HPV infection that incorporates both vaccination and screening was developed for Japan. The modelled intervention, a bivalent HPV vaccine with a 100% lifetime vaccine efficacy and 80% vaccine coverage, given to a cohort of 12-year-old Japanese girls in conjunction with the current screening program, was compared with screening alone in terms of costs and effectiveness. A discount rate of 5% was applied to both costs and utilities where relevant. RESULTS: Vaccination alongside screening compared with screening alone is associated with an incremental cost-effectiveness ratio (ICER) of US$20315 per quality-adjusted-life-year gained if 80% coverage is assumed. The ICER at 5% coverage with the vaccine plus screening, compared with screening alone, is US$1158. CONCLUSION: The cost-effectiveness results suggest that the addition of a HPV vaccination program to Japan's cervical cancer screening program is highly likely to prove a cost-effective way to reduce the burden of cervical cancer, precancerous lesions and HPV16/18-related diseases.

Efficacy of a parainfluenza virus 5 (PIV5)-based H7N9 vaccine in mice and guinea pigs: antibody titer towards HA was not a good indicator for protection.

H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5), an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7) and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9) in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP) conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively.

Trivalent live attenuated influenza-simian immunodeficiency virus vaccines: efficacy and evolution of cytotoxic T lymphocyte escape in macaques.

There is an urgent need for a human immunodeficiency virus (HIV) vaccine that induces robust mucosal immunity. CD8+ cytotoxic T lymphocytes (CTLs) apply substantial antiviral pressure, but CTLs to individual epitopes select for immune escape variants in both HIV in humans and SIV in macaques. Inducing multiple simian immunodeficiency virus (SIV)-specific CTLs may assist in controlling viremia. We vaccinated 10 Mane-A1*08401+ female pigtail macaques with recombinant influenza viruses expressing three Mane-A1*08401-restricted SIV-specific CTL epitopes and subsequently challenged the animals, along with five controls, intravaginally with SIVmac251. Seroconversion to the influenza virus vector resulted and small, but detectable, SIV-specific CTL responses were induced. There was a boost in CTL responses after challenge but no protection from high-level viremia or CD4 depletion was observed. All three CTL epitopes underwent a coordinated pattern of immune escape during early SIV infection. CTL escape was more rapid in the vaccinees than in the controls at the more dominant CTL epitopes. Although CTL escape can incur a "fitness" cost to the virus, a putative compensatory mutation 20 amino acids upstream from an immunodominant Gag CTL epitope also evolved soon after the primary CTL escape mutation. We conclude that vaccines based only on CTL epitopes will likely be undermined by rapid evolution of both CTL escape and compensatory mutations. More potent and possibly broader immune responses may be required to protect pigtail macaques from SIV.

Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

Psychometric data on the mathematics self-efficacy scale

Descriptive measurement reliability and validity data are reported on scores from the Mathematics Self-Efficacy Scale (MSES) in two contexts—class and test—for a sample of 302 Australian high school students. Summated scores on the MSES correlated r = .74, and together these items yielded one component that explained 49% of the variance. MSES scores demonstrated internal reliability for both class and test (Cronbach alphas = .86 and .90). Statistically significant correlations between MSES scores, past mathematics grades, and Marsh’s Self-Description Questionnaire III (Math) were used to indicate the convergent validity of scores for the MSES. Discriminant validity of the MSES scores was suggested by the lack of significant correlations between the MSES measures and students’ desired English grades. Statistically significant correlations between MSES scores and students’ desired mathematics grades indicated concurrent validity of the MSES measures. A statistically significant difference between class and test scores supported Bandura’s prescription for context specificity in efficacy research.

Emotional intelligence and teacher self efficacy : the contribution of teacher status and length of experience

Practicing teachers and principals in selected Government schools in Victoria provided data on their levels of emotional intelligence and teacher efficacy beliefs. The data supported the theoretical expectation of a linkage between emotional intelligence and teacher self efficacy. Regression analyses showed that neither gender nor age moderated this relationship. However length of teaching experience and current status add significant direct effects on predicting teacher self efficacy but did not moderate the relationship between emotional intelligence and teacher self efficacy. These findings are significant as this now demonstrates a relationship between levels of emotional intelligence in teachers, their self efficacy beliefs and teacher effectiveness.

Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases : implications for vaccine and drug design

Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.

Fresh kids: the efficacy of a health promoting schools approach to increasing consumption of fruit and water in Australia

The Fresh Kids programme utilized the Health Promoting Schools (HPSs) framework to design a whole-of-school, multifaceted intervention targeting specific behaviours to promote healthy eating and reduce the risk factors associated with childhood obesity. The aim of the programme was to evaluate the effectiveness of the HPS framework to increase fruit and water consumption among primary school-aged children over a 2-year period. The study design was an interrupted time series. Four primary schools in the inner west of Melbourne, Australia, participated in the programme intervention. Baseline data were collected using a lunch box audit to assess the frequency of children with fresh fruit, water and sweet drinks, either brought from home or selected from canteen lunch orders. The lunch box audit was repeated periodically for up to 2 years following programme implementation to assess the sustainability of dietary changes. Across all participating schools, significant increases between 25 and 50% were observed in the proportion of children bringing fresh fruit. Similarly, all schools recorded increases between 15 and 60% in the proportion of students bringing filled water bottles to school and reductions between 8 and 38% in the proportion of children bringing sweet drinks. These significant changes in dietary patterns were sustained for up to 2 years following programme implementation. Targeting key nutrition behaviours and using the HPS framework is an effective and simple approach which could be readily implemented in similar childhood settings. Effective strategies include facilitating organizational change within the school; integrating curriculum activities; formalizing school policy and establishing project partnerships with local community nutrition and dietetic services.

Reactions to increased workload: effects on professional efficacy of nurses

Research findings support the idea that workload is a significant stressor associated with a variety of deleterious psychological reactions, including burnout, in several different samples of workers. A theoretical model is put forth in the present study in which workload is seen as contributing to distress and depression. Increasingly, organisations are experiencing changes as a result of extensive downsizing, restructuring, and merging. As a result of fiscal restraint, hospitals have been forced to merge, close, downsize, and restructure. Workloads have increased among hospital staff, particularly nurses. This study applies a theoretical model to the understanding of the impact of workload on nurses employed in hospitals experiencing downsizing, particularly on their distress, burnout, and depression. Respondents were 488 nurses who were employed in hospitals that were undergoing restructuring and in which units had already been closed as a result of restructuring. Results of structural equation modeling showed that the data partially fit the model and that workload contributed substantially to levels of depression through distress reactions. Further results showed that cynicism, anger, and emotional exhaustion significantly operationalised distress reactions. This study is unique theoretically in linking anger, cynicism, and emotional exhaustion in a single model that predicts distress levels from workload. The findings that anger, cynicism, and emotional exhaustion operationalised distress indicate the importance of studying patterns of negative reactions and their consequences for depression. Implications of the results are discussed for interventions that can be taken by organisations in order to reduce workloads.

The role of alcohol expectancy and drinking refusal self-efficacy beliefs in university student drinking

Aims: University student alcohol misuse is a considerable problem. Alcohol expectancy research has contributed significantly to our understanding of problem drinking in young adults. Most of this research has investigated positive expectancy alone. The current study utilized two measures of alcohol expectancy, the alcohol expectancy questionnaire (AEQ) and the drinking expectancy profile [consisting of the drinking expectancy questionnaire (DEQ) and the drinking refusal self-efficacy questionnaire] to predict severity of alcohol dependence, frequency of drinking, and the quantity of alcohol consumed per occasion. Methods: Measures of drinking behaviour and alcohol expectancy were completed by 174 undergraduate university students. Results: Positive alcohol expectancy factors accounted for significant variance in all three drinking indices, with the DEQ adding additional variance to AEQ scores on frequency and severity of alcohol dependence indices. Negative expectancy did not add incremental variance to the prediction of drinking behaviour in this sample. Drinking refusal self-efficacy and dependence beliefs added additional variance over positive and negative expectancies in the prediction of all three drinking parameters. Conclusions: Positive expectancy and drinking refusal self-efficacy were strongly related to university student drinking. The incorporation of expectancy as a means of informing prevention approaches in tertiary education shows promise.