Influenza vaccination of elderly: relaunch time.

Influenza can be a serious disease and constitutes a threat to the population. Every year, seasonal influenza epidemics affect about 5-15% of the world's population. Some frail categories (such as the elderly) can develop complications, request hospitalization, and may die. In order to reduce the medical, social and economic burden of influenza, vaccination is recommended by many health authorities worldwide. Italy has a national programme of influenza vaccination which targets specific categories, such as subjects with chronic conditions, pregnant women, healthcare workers and those over 65 years old. Despite this opportunity for prevention, however, vaccination coverage in Italy does not reach the minimum recommended threshold of 75%. This paper reports some interventions that can improve coverage rates of the elderly, such as "tailor-made" information campaigns, healthcare workers training and the adoption of innovative communication strategies in order to implement vaccination strategies that take into account the needs of the elderly population, the involvement of elderly people's associations in awareness-raising activities and strengthening the role of general practitioners in promoting influenza vaccination.

Analysis of influenza vaccination coverage among the elderly in Genoa (Italy) based on a deprivation index, 2009-2013.

INTRODUCTION: The elderly suffer the most influenza-related complications, and 90% of deaths due to influenza occur in older subjects. Consequently, the elderly are among the main targets of influenza vaccination campaigns. The use of deprivation indexes can help to identify subgroups with lower vaccination uptake. This study analyzed influenza vaccination coverage in elderly persons living in Genoa (Italy) in relation to a local Index of Socio-Economic and Health Deprivation (SEHDI) in order to identify population subgroups needing specific intervention to improve vaccination coverage. METHODS: The study targeted subjects aged ≥ 65 years living in Genoa in the period 2009-2013. Information on vaccination coverage was provided by general practitioners and Local Health Units. A combination of linear regression, factor analysis and cluster analysis was used to construct the SEHDI at Census Tract (CT) level, on the basis of data from the 2011 Italian census. RESULTS: In 2011, people aged ≥ 65 years accounted for the 27.7% of the population of Genoa. Most elderly subjects were assigned to either the medium (45.3%) or medium-high (32%) deprivation groups, while the percentages in the extreme tails were low (3.6% high deprivation; 1.3% low deprivation). Significant, non-linear (p < 0.05 NL) relationships were observed in both sexes with regard to mortality due to all respiratory diseases (RD) and chronic obstructive pulmonary disease (COPD), with the highest Standardized Mortality Ratio (SMR) values in women in the high deprivation group of women (1.81, p < 0.05 RD; 1.79, p < 0.05 COPD). The SMRs for influenza and pneumonia showed a positive linear trend in women (p < 0.05) with the highest value in the high deprivation group (1.97, p < 0.05), while in men the trend was NL (p < 0.05). A positive linear trend (p < 0.05) was found with regard to vaccination coverage, which grew weakly as deprivation increased, up to the medium-high deprived group (from 34.6% to 44.4%). However, the high deprivation group showed the lowest value (33.3%). CONCLUSIONS: The results revealed a relationship between deprivation and influenza vaccination coverage in the elderly. This finding should be taken into account in the organization of vaccination campaigns and should prompt differentiated intervention in each local area.

Epidemiology of herpes simplex virus type 1 and 2 in Italy: a seroprevalence study from 2000 to 2014.

Herpes simplex viruses (HSV) are among the most widespread causative agents of human viral infections. HSV-2 is one of the commonest causes of genital disease, while HSV-1 is associated primarily with orolabial ulceration; however, recent changes in HSV epidemiology showed an increase in genital and neonatal herpes particularly caused by HSV-1. The main purpose of this study was to assess the seroprevalence of HSV-1 and HSV-2 in a random population in Siena (central Italy) in 2000, 2005 and 2013-2014 and in Bari (southern Italy) in 2005. Moreover, a preliminary study was conducted to investigate the spread of HSV infection in a population of pregnant women and infants in Bari in 2003, 2004 and 2005. Human serum samples were tested for the presence of specific anti-HSV-1 and anti-HSV-2 IgG antibodies using a commercially available ELISA test. For the primary purpose, seroprevalence rates observed in Siena were compared over the years sampled and with the seroprevalence rate found in Bari. Results of seroprevalence in Siena show a decreased trend for both viruses, especially in adolescents and young adults; moreover, HSV-2 seroprevalence rates found in the two cities suggest geographical differences. For the secondary purpose, prevalence rates among pregnant women were compared with the seroprevalence found in women of the general population. No significant difference in prevalence rates were found among pregnant women, while results indicate both viruses are a source of infection in infants.

Overview of the impact of Typhoid and Paratyphoid fever. Utility of Ty21a vaccine (Vivotif®).

Cases of diarrhoeal disease number from 1.7 to 5 billion per year worldwide. One of the main causes of diarrhoeal disease is typhoid fever, which is a potentially life-threatening multi-systemic illness. According to the most recent estimates, a total of 26.9 million typhoid fever episodes occurred in 2010. The geographical distribution of the disease differs widely; in developed countries, the incidence rate per 100,000 per year varies from < 0.1 to 0.3, and the disease mainly affects people who travel to endemic areas located in low- and middle-income countries. Low- and middle-income countries are mainly affected owing to the lack of clean water and proper sanitation. In the fight against this plague, prevention is fundamental, and vaccination against typhoid is an effective measure. Vivotif® is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe. It is indicated for adults and children from 5 years of age upwards. Specifically, in the most developed countries, vaccination is suggested for highrisk population groups and particularly for international travellers to destinations where the risk of contracting typhoid fever is high. It must also be borne in mind that international travel is increasing. Indeed, international tourist arrivals totalled 1,184 million in 2015 and, on the basis of current trends, international travel is expected to grow by 3-4% in 2017. Vivotif® appears to be a powerful means of disease prevention, the importance of which is highlighted by the spread of antibiotic-resistant strains of Salmonella typhy (S. typhi).

Knowledge, attitudes and behaviors of the Italian population towards Neisseria meningitidis, Streptococcus pneumoniae and HPV diseases and vaccinations: A cross-sectional multicentre study.

OBJECTIVES: This study addressed knowledge of Streptococcus pneumoniae, Neisseria meningitidis and human papillomavirus (HPV), and attitudes and behaviours towards vaccines against them. STUDY DESIGN: This is a cross-sectional, multicentre study. METHODS: Data were collected through a questionnaire administered to 530 adults who accessed four Departments of Prevention of the Italian National Health Service in 2013. RESULTS: Less than 50% of people gave the right answer to all the questions concerning the three diseases, but 96.2%, 94% and 92.7% agreed with the importance of vaccination against N. meningitidis, S. pneumoniae and HPV, respectively, and 58.4% expressed own willingness to have their children vaccinated with N. meningitidis B vaccine. The attitude towards vaccination was more positive in women for N. meningitidis and in people having children for HPV. Furthermore, individuals giving correct answers to all knowledge items were more in favour of both HPV and S. pneumoniae vaccination. A total of 68.8%, 82.6% and 84.5% of respondents vaccinated their own children against N. meningitidis C, S. pneumoniae and HPV, respectively. About 50% of the respondents reported paediatricians' or other health professionals' recommendations as the main reason for vaccination. CONCLUSIONS: Vaccinations may be promoted through actions aimed at increasing citizens' knowledge. Health professionals should be educated to actively provide information on vaccinations in a clear, comprehensive and effective way.

Influenza vaccination: from epidemiological aspects and advances in research to dissent and vaccination policies.

Influenza is a serious public health problem, since seasonal epidemics affect approximately 5-10% of the population and thus give rise to a heavy social and healthcare burden. The heavy burden of disease is due to several factors, one of which is the biological features of the pathogen. Indeed influenza viruses display high mutation rates and undergo frequent genetic reassortment. Minor variations cause seasonal epidemics and major variations, which result from the hybridization of viruses typical of different animal species, can lead to pandemics. Vaccination remains the most efficacious means of mitigating the harmful healthcare and social effects of influenza. Influenza vaccines have evolved over time in order to offer broader protection against circulating strains. Trivalent vaccines containing two A viruses and one B virus are currently available. However, given the co-circulation of both B virus lineages (B/Yamagata and B/Victoria), quadrivalent vaccines have recently been developed. The new quadrivalent vaccines constitute a great advance, in that they can offer broader strain coverage. Despite the availability of effective and safe influenza vaccines, the Italian public's trust in vaccination has declined and, in the last few years, influenza vaccination coverage rates have decreased both among the elderly and among at-risk adults. It is therefore necessary that users, in their own interests, regain trust in this important means of disease prevention. In order to mitigate the damage wreaked by influenza, it seems important to: (i) improve clinical-epidemiological and virological surveillance of the disease; (ii) promote the development of new efficacious vaccines, as has recently been done through the introduction of the quadrivalent vaccine; (iii) extend free vaccination to the entire population, as in the US and Canada; (iv) ensure that general healthcare professionals are properly informed and always updated with regard to vaccination; (v) promote public campaigns to raise the population's awareness of the importance of vaccination; (vi) inform politicians and other decision-makers of scientific results in the field of vaccination; (vii) fight the antivaccination lobbies with every available weapon.

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines.

In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains.

How can the results of Health Technology Assessment (HTA) evaluations applied to vaccinations be communicated to decision-makers and stakeholders? The ISPOR Rome Chapter Project.

HTA is considered the most comprehensive and transparent method of supporting decision-makers in their choices in Public Health. HTA on vaccines is being performed by many experts. However, they often present their studies to colleagues, but not to decisionmakers, who should be the main target and current users. It is therefore crucial to improve the transfer of scientific data to decision- makers and all stakeholders. The aims of the present project are: 1) to set up a team of experts to collect economic evaluations and HTA studies on vaccines and assess their actual use in decision-making processes; 2) to constitute regional working groups in order to identify the critical aspects of the communication process and identify the most appropriate method of data transfer. Systematic reviews of economic evaluations and HTA on vaccines and their actual use in decision-making will be used to draw up the basic documents for discussion by the 3 regional working boards. The working groups will discuss the current scientific evidence and communication methods and will try to implement a model of technology assessment with well-defined and objective criteria, in order to better fit pharmaco-economic and HTA methods to the field of vaccinations. Improving the transfer of HTA results to stakeholders, particularly decision-makers, will enable decisions to be taken on the basis of scientific evidence, and appropriate, sustainable actions to be undertaken.

Impact of different scoring algorithms applied to multiple-mark survey items on outcome assessment: an in-field study on health-related knowledge.

INTRODUCTION: Health-related knowledge is often assessed through multiple-choice tests. Among the different types of formats, researchers may opt to use multiple-mark items, i.e. with more than one correct answer. Although multiple-mark items have long been used in the academic setting - sometimes with scant or inconclusive results - little is known about the implementation of this format in research on in-field health education and promotion. METHODS: A study population of secondary school students completed a survey on nutrition-related knowledge, followed by a single- lecture intervention. Answers were scored by means of eight different scoring algorithms and analyzed from the perspective of classical test theory. The same survey was re-administered to a sample of the students in order to evaluate the short-term change in their knowledge. RESULTS: In all, 286 questionnaires were analyzed. Partial scoring algorithms displayed better psychometric characteristics than the dichotomous rule. In particular, the algorithm proposed by Ripkey and the balanced rule showed greater internal consistency and relative efficiency in scoring multiple-mark items. A penalizing algorithm in which the proportion of marked distracters was subtracted from that of marked correct answers was the only one that highlighted a significant difference in performance between natives and immigrants, probably owing to its slightly better discriminatory ability. This algorithm was also associated with the largest effect size in the pre-/post-intervention score change. DISCUSSION: The choice of an appropriate rule for scoring multiple- mark items in research on health education and promotion should consider not only the psychometric properties of single algorithms but also the study aims and outcomes, since scoring rules differ in terms of biasness, reliability, difficulty, sensitivity to guessing and discrimination.

Meningococcal B vaccination strategies and their practical application in Italy.

Immunisation against meningococcal meningitis has a long history, which has passed through several phases: the studies by Flexner, extraction of the polysaccharide capsule, the development of monovalent and multivalent conjugate vaccines, the outer membrane vesicle vaccines up to the development of effective and safe vaccines for meningococcal B invasive disease through the application of the techniques of molecular biology and reverse vaccinology. The new available vaccines are Bexsero® and Trumenba®. Bexsero ® has been approved and is available in Europe, the USA, Canada, Australia and Chile, and is currently under review in Brazil for the prevention of MenB invasive disease in subjects ≥ 2 months. Trumemba® is currently approved only in the USA, for use in adolescents and young adults. At present, the greatest obstacle to the extensive use of these vaccines in industrialised countries is the high cost and the need administer multiple doses in infants. However, in some European countries and in some Italian Regions, strategies (free and active call) to fight the disease through vaccination (Bexsero®) are already in place.

The "urban myth" of the association between neurological disorders and vaccinations.

In modern society, a potentially serious adverse event attributed to a vaccination is likely to be snapped up by the media, particularly newspapers and television, as it appeals to the emotions of the public. The widespread news of the alleged adverse events of vaccination has helped to create the "urban myth" that vaccines cause serious neurological disorders and has boosted antivaccination associations. This speculation is linked to the fact that the true causes of many neurological diseases are largely unknown. The relationship between vaccinations and the onset of serious neuropsychiatric diseases is certainly one of coincidence rather than causality. This claim results from controlled studies that have excluded the association between vaccines and severe neurological diseases, therefore it can be said, with little risk of error, that the association between modern vaccinations and serious neurological disorders is a true "urban myth".

Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus.

In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories.

Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: Influenza life-cycle and currently available drugs.

Influenza is a contagious respiratory acute viral disease characterized by a short incubation period, high fever and respiratory and systemic symptoms. The burden of influenza is very heavy. Indeed, the World Health Organization (WHO) estimates that annual epidemics affect 5-15% of the world's population, causing up to 4-5 million severe cases and from 250,000 to 500,000 deaths. In order to design anti-influenza molecules and compounds, it is important to understand the complex replication cycle of the influenza virus. Replication is achieved through various stages. First, the virus must engage the sialic acid receptors present on the free surface of the cells of the respiratory tract. The virus can then enter the cells by different routes (clathrin-mediated endocytosis or CME, caveolae-dependent endocytosis or CDE, clathrin-caveolae-independent endocytosis, or macropinocytosis). CME is the most usual pathway; the virus is internalized into an endosomal compartment, from which it must emerge in order to release its nucleic acid into the cytosol. The ribonucleoprotein must then reach the nucleus in order to begin the process of translation of its genes and to transcribe and replicate its nucleic acid. Subsequently, the RNA segments, surrounded by the nucleoproteins, must migrate to the cell membrane in order to enable viral assembly. Finally, the virus must be freed to invade other cells of the respiratory tract. All this is achieved through a synchronized action of molecules that perform multiple enzymatic and catalytic reactions, currently known only in part, and for which many inhibitory or competitive molecules have been studied. Some of these studies have led to the development of drugs that have been approved, such as Amantadine, Rimantadine, Oseltamivir, Zanamivir, Peramivir, Laninamivir, Ribavirin and Arbidol. This review focuses on the influenza life-cycle and on the currently available drugs, while potential antiviral compounds for the prevention and treatment of influenza are considered in the subsequent review.

Tobacco smoking among students in an urban area in Northern Italy.

INTRODUCTION: Tobacco smoking, which usually begins in teenage, is one of the most important lifestyle risk factors for chronic diseases and a major public health problem worldwide. The aims of the study were to determine the prevalence of tobacco smoking and the mean age of initiation among adolescents in Genoa (Italy) and to identify some socio-demographic predictors that could be associated with the onset of smoking. MATERIALS AND METHODS: 2,301 randomly selected students (14-19 years old) in Genoa completed an ad hoc questionnaire. The Kaplan-Meier method was used to evaluate the instantaneous risk of experimenting with smoking. A multivariate logistic regression model was used to determine whether current or previous smoking status was associated with socio-demographic characteristics. RESULTS: 59.5% of respondents had tried smoking, while 35.6% defined themselves as current smokers. No difference in current smoking prevalence emerged between males and females (35.2% and 35.9%, respectively, p = 0.83). The mean age on initiation was 13.5 years for males and 13.9 years for females. The instantaneous probability of trying smoking changed with age, reaching a maximum at 14 years. Subjects who tried smoking before this age were more inclined to continue smoking. The probability of being a current smoker was significantly higher among students from unmarried-parent families and those attending vocational and technical secondary schools. CONCLUSIONS: There is a great need for the activation of new health promotion interventions and enforcement of those already existing, in order to raise awareness of the damage caused by smoking among adolescents, especially those belonging to high-risk groups.

New versus old meningococcal group B vaccines: how the new ones may benefit infants & toddlers.

Invasive disease caused by Neisseria meningitidis is associated with high mortality and high disability rates and mainly affects children under one year of age. Vaccination is the best way to prevent meningococcal disease, especially in infants and toddlers. The introduction of massive meningococcal serogroup C vaccination has drastically reduced the incidence of disease caused by this serogroup, and serogroup B has now become the main causative agent in several industrialized countries. The first serogroup B vaccines, which were used for more than two decades, were based on outer membrane vesicles and proved to be protective only against specific epidemic strains in Cuba, Norway, Brazil and New Zealand. Moreover, these often elicited a scant immune response in young children. Innovative genomics-based reverse vaccinology subsequently enabled researchers to identify genes encoding for surface proteins that are able to elicit a strong immune response against several B strains. This important discovery led to the development and recent approval in Europe of the four-component meningococcal serogroup B (4CMenB) vaccine. Large clinical trials have shown high immunogenicity and tolerability and acceptable safety levels of 4CMenB in infants and toddlers. This vaccine is expected to cover a large number of circulating invasive strains and may also be efficacious against other serogroups. Young children are particularly vulnerable to the devastating consequences of meningococcal disease. Given the high performance of 4CMenB and its non-interference with routine vaccinations, this age-group will be the first to benefit from the introduction of this vaccine.

Neisseria meningitidis, pathogenetic mechanisms to overcome the human immune defences.

Neisseria meningitidis is hosted only by humans and colonizes the nasopharynx; it survives in the human body by reaching an equilibrium with its exclusive host. Indeed, while cases of invasive disease are rare, the number of asymptomatic Neisseria meningitides carriers is far higher. The aim of this paper is to summarize the current knowledge of survival strategies of Neisseria meningitides against the human immune defences. Neisseria meningitidis possesses a variety of adaptive characteristics which enable it to avoid being killed by the immune system, such as the capsule, the lipopolysaccharide, groups of proteins that block the action of the antimicrobial proteins (AMP), proteins that inhibit the complement system, and components that prevent both the maturation and the perfect functioning of phagocytes. The main means of adhesion of Neisseria meningitides to the host cells are Pili, constituted by several proteins of whom the most important is Pilin E. Opacity-associated proteins (Opa) and (Opc) are two proteins that make an important contribution to the process of adhesion to the cell. Porins A and B contribute to neisserial adhesion and penetration into the cells, and also inhibit the complement system. Factor H binding protein (fhbp) binds factor H, allowing the bacteria to survive in the blood. Neisserial adhesin A (NadA) is a minor adhesin that is expressed by 50% of the pathogenic strains. NadA is known to be involved in cell adhesion and invasion and in the induction of proinflammatory cytokines. Neisserial heparin binding antigen (NHBA) binds heparin, thus increasing the resistance of the bacterium in the serum.

Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.

BACKGROUND: Although influenza vaccination is widely recommended for immunosuppressed people, the same immune dysfunction that can increase the risk of contracting influenza might also compromise vaccine effectiveness, especially during pandemics. Clinical data have highlighted the role of adjuvants in improving vaccine efficacy. As uremic patients are especially vulnerable to infections, it is recommended that they should be vaccinated yearly against influenza. This paper presents the results of a pilot clinical trial, conducted in hemodialyzed patients with an adjuvated pandemic H1N1v influenza vaccine alone and combined with Thymosin-alpha 1. METHODS: Subjects were subdivided into 3 treatment groups receiving: the adjuvated pandemic influenza vaccine (Focetria) only (first treatment group), and the Vaccine+Thymosin alpha 1 (Zadaxin) at a dose of 3.2 and 6.4 mg (second and third treatment groups respectively). The immunoresponse was assessed on days 0, 21, 42, 84 and 168 after vaccine administration by means of Hemagglutination Inhibition (HI), Microneutralization (MN) and Single Radial Hemolysis (SRH) assays. The CHMP regards HI as the gold standard test to evaluate the immune response to influenza vaccines before influenza vaccines are licensed. The CHMP criteria are slightly different in adults (18-60-year-old subjects) and the elderly (>60 years old). Indeed, 40% of seroconversion, 70% of subjects seroprotected 21 days after vaccination, and a 2.5-fold increase in GMR (Geometric Mean Ratio) are required in adults, while in the elderly, the corresponding threshold values are: 30%, 60% and a 2-fold increase. All these criteria must be met for the licensing of a pandemic influenza vaccine. Safety evaluation was performed by means of Adverse Event (AE) recording, laboratory assays (hematology and chemistry), electrocardiogram, and assessment of vital signs. RESULTS: Three populations were considered: Intention-To-Treat (ITT) (94 patients), Per Protocol (PP) (82 patients), and Safety population (99 patients). With regard to the Geometric Mean Titer (GMT) and the Geometric Mean Ratio (GMR) of HI on Day 21 in the ITT population, both "Vaccine+Thymosin alpha 1" groups presented better results than the "Vaccine only" group. A large proportion of ITT patients in the two Vaccine+Thymosin alpha 1 groups achieved seroconversion by Day 21. On Day 42, the decrease in the GMT of HI was greater in the Vaccine+Thymosin alpha 1 groups than in the vaccine only group. Similar results were obtained in the PP population. The CHMP criteria were fully met in the groups treated with Vaccine+Thymosin alpha 1. No AE was found to be related to Thymosin alpha 1 nor to the Focetria vaccine. CONCLUSIONS: Although further studies in larger hemodialyzed populations are necessary, it can be concluded that Thymosin alpha 1 enhanced the immunogenicity of the pandemic influenza vaccine used. Moreover, it proved safe and well tolerated, and did not affect hematology or blood-chemistry values.

Live attenuated influenza vaccine--a review.

Owing to the variability of influenza viruses, vaccine composition needs to be up-dated annually. As many variables can influence their efficacy, vaccines are still considered "sub-optimal". Many studies have been carried out in recent years to improve vaccines. In particular, researchers and vaccine-producing corporations have focused on developing a live vaccine. Among the candidate vaccines, the strain developed by Maassab has recently been licensed in the USA and Europe, after extensive investigation. This vaccine is safe and well tolerated, and has shown very good genetic stability. Although vaccine recipients are able to spread the virus, transmission to close contacts is practically non-existent. Studies on cold-adapted attenuated influenza vaccines have demonstrated that such vaccines are effective, and sometimes more effective than inactivated influenza vaccines. Cold-adapted attenuated influenza vaccines therefore appear to be an important weapon against influenza. However, a more widespread use of these vaccines is to be recommended, especially in children, as the more acceptable way of administration can favour parental compliance.

Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.

Influenza constitutes a serious problem for healthcare and social services worldwide, owing to its pattern and the severity of its complications in some categories of subjects at risk, such as the elderly and immunocompromised individuals. The only really effective means of combating influenza is vaccination. The elderly and immunocompromised subjects are refractory or low responders to vaccination. The need for ever more immunogenic and efficacious influenza vaccines, especially for subjects at risk, has prompted the development of adjuvated vaccines. With a view to enhancing the immune response in the elderly and in subjects at risk, the possibility of co-administering immunostimulants as Thymosin alpha-1 (Talpha1) with influenza vaccines has been investigated. Talpha1 is a biologically active peptide made up of 28 amino acids that can enhance T-cells, dendritic cell and antibody responses, modulate cytokines and chemokines production. Several studies were conducted and showed that Talpha1 ameliorate the performanc of influenza vaccination in elderly and subjects at risk. Although further studies on co-adjuvants are necessary, the future prospects of producing ever more efficacious influenza vaccines appear very promising.