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1.  Molecular and Serological Diversity of Neisseria meningitidis Carrier Strains Isolated from Italian Students Aged 14 to 22 Years 
Journal of Clinical Microbiology  2014;52(6):1901-1910.
Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.
PMCID: PMC4042792  PMID: 24648565
2.  Do the omeprazole family compounds exert a protective effect against influenza-like illness? 
BMC Infectious Diseases  2014;14:297.
Infections by influenza viruses place a heavy burden on public health and economies worldwide. Although vaccines are the best weapons against influenza, antiviral drugs could offer an opportunity to alleviate the burden of influenza. Since omeprazole family compounds block the “proton pump”, we hypothesized that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses.
A matched case-control study was performed in 2010-2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of Influenza-like Illness (ILI); 254 case-control pairs were recruited. A multivariable conditional logistic regression analysis was used to assess the association between the prevention of ILI and the administration of omeprazole family compounds. The interaction between omeprazole family compounds and influenza vaccination was also examined.
After control for potential confounders, subjects treated with omeprazole family compounds displayed a lower risk of catching ILI (ORadj = 0.29, 95% CI: 0.15-0.52). The risk of ILI in unvaccinated non-OFC users was about six times than that in vaccinated OFC users.
Although confirmation is necessary, these results suggest that omeprazole family compounds could be profitably used in the prevention of ILI.
PMCID: PMC4051147  PMID: 24889553
Influenza-like illness (ILI); Omeprazole family compounds; Epidemiology; Prevention
3.  The Impact of HPV Female Immunization in Italy: Model Based Predictions 
PLoS ONE  2014;9(3):e91698.
The Human Papillomavirus (HPV) is a sexually transmitted virus that causes cervical cancer. Since 2008 a vaccination program targeting 12-year-old girls has been initiated in Italy, backing up the cervical screening program already active since 1996. We propose a mathematical model of HPV transmission dynamics with the aim of evaluating the impact of these prevention strategies. The model considers heterosexual transmission of HPV types 16 and 18, structured by sex, age and sexual activity level, where transition to sexual activity is explicitly modeled from recent survey data. The epidemiological structure is a hybrid SIS/SIR, where a fraction of individuals recovering from infection develops permanent immunity against reinfection. Infections may progress to cervical lesions and cancer and heal spontaneously or upon treatment. Women undergoing hysterectomy (either after treatment of HPV lesions or by other causes) also transmit HPV infection. The model fits well both the age-specific prevalence of HPV infections and the incidence of cervical cancers in Italy, and accurately reproduces the decreasing trend in cancer incidence due to the introduction of the screening program. The model predicts that if the screening coverage is maintained at current levels, even in the absence of vaccination, such trend will continue in the next few decades, eventually plateauing at 25% below the current level. The additional initiation of routine vaccination targeting 12-year-old girls will further reduce cervical cancer incidence by two thirds at equilibrium, under realistic assumptions of 70% coverage and a duration of protective immunity of 50 years. If catch-up immunization of 25-year-old women at first cervical screening is also introduced, about 3,000 cervical cancer cases overall can be averted, corresponding to 9.6% of all cases expected in the scenario without catch-up. We conclude that HPV vaccination in addition to cervical screening will significantly reduce the burden of cervical cancer in Italy.
PMCID: PMC3950270  PMID: 24618824
4.  Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy 
Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy.
Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose indications include all pneumococcal diseases in subjects ≥ 50 y), the model calculated also the possible impact of vaccination on CAP cases (non-bacteraemic), considering the rate of this disease due to S. pneumoniae. The results of the analysis show that, in Italy, an age-based PCV13 vaccination program in elderly people is cost-effective from the payer perspective, with costs per QALY ranging from 17,000 to 22,000 Euro, according to the adopted vaccination strategy. The subsequent PPV23 offer results in an increment of costs per QALY (from 21,000 to 28,000 Euro, according to the vaccination strategy adopted). Pneumococcal vaccination using the conjugate vaccine turned out to be already favorable in the second year of implementation, with incremental costs per QALY comparable to those of other already adopted prevention activities in Italy (for instance, universal HPV vaccination of 12 y-old girls), with further benefits obtained when extending the study period beyond the 5-y horizon of our analysis.
PMCID: PMC3891731  PMID: 23295824
pneumococcal conjugate vaccine; elderly; economic evaluation; cost-effectiveness; pneumococcal disease
5.  Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy? 
BMC Infectious Diseases  2013;13:575.
Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females.
The study was performed in 2010. Women aged 16–26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay.
Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16–17 age-class, 15.4 in the 18–20 age-class, 21.9% in the 21–23 age-class, and 15.5% in the 24–26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16–17 years); HPV prevalence subsequently declined and stabilized.
The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively.
Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored.
PMCID: PMC4029487  PMID: 24313984
Papillomavirus; HPV; Cervical cancer prevention; Vaccination; HPV epidemiology; Young women
6.  Detection and Genotyping of Human Papillomavirus in Urine Samples from Unvaccinated Male and Female Adolescents in Italy 
PLoS ONE  2013;8(11):e79719.
The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS®-miniMAG®, bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively.
PMCID: PMC3821858  PMID: 24255711
7.  Use of different subjective health indicators to assess health inequalities in an urban immigrant population in north-western Italy: a cross-sectional study 
BMC Public Health  2013;13:1006.
Despite the steady growth of the immigrant population in Italy, data on the health status of immigrants are scarce. Our main goals were to measure Health-Related Quality of Life (HRQoL), Self-Rated Health (SRH) and morbidity among immigrants in Genoa. We aimed to assess the relative contribution of some social, structural and behavioral determinants to “within-group” health disparities.
We enrolled 502 subjects by means of snowball sampling. The SF-12 questionnaire, integrated with socio-demographic and health-related items, was used. Multivariate logistic and Poisson regression models were applied in order to identify characteristics associated with poor SRH, lower SF-12 scores and prevalence of self-reported morbidities.
Subjects showed relatively moderate levels of HRQoL (median physical and mental scores of 51.6 and 47.3, respectively) and about 15% of them rated their health as fair or poor. Lower scores in the physical dimension of HRQoL were associated with the presence of morbidities and immigration for work and religious reasons, while those who had migrated for religious and family reasons displayed a lower probability of lower scores in the mental dimension of HRQoL. Poor SRH was associated with female gender, overweight/obesity and presence of morbidities. Moreover, compared with immigrants from countries with a low human development index, immigrants from highly developed societies showed significantly lower odds of reporting poor SRH. About one-third of respondents reported at least one medical condition, while the prevalence of multi-morbidity was 10%. Females, over 45-year-olds, overweight and long-term immigrants had a higher prevalence of medical conditions.
Our study confirms the presence of health inequalities within a heterogeneous immigrant population. HRQoL, SRH and morbidity are valid, relatively rapid and cheap tools for measuring health inequalities, though they do so in different ways. These indicators should be used with caution and, if possible, simultaneously, as they could help to identify and to monitor more vulnerable subjects among immigrants.
PMCID: PMC4016025  PMID: 24156544
Italy; Immigrants; Subjective health indicators; Health-related quality of life (HRQoL); Self-rated health (SRH); Health inequalities
8.  An overview of current and potential use of information and communication technologies for immunization promotion among adolescents 
Human Vaccines & Immunotherapeutics  2013;9(12):2634-2642.
Information and communication technologies (ICT), such as the Internet or mobile telephony, have become an important part of the life of today’s adolescents and their main means of procuring information. The new generation of the Internet based on social-networking technologies, Web 2.0, is increasingly used for health purposes by both laypeople and health professionals. A broad spectrum of Web 2.0 applications provides several opportunities for healthcare workers, in that they can reach large numbers of teenagers in an individualized way and promote vaccine-related knowledge in an interactive and entertaining manner. These applications, namely social-networking and video-sharing websites, wikis and microblogs, should be monitored in order to identify current attitudes toward vaccination, to reply to vaccination critics and to establish a real-time dialog with users. Moreover, the ubiquity of mobile telephony makes it a valuable means of involving teenagers in immunization promotion, especially in developing countries.
PMCID: PMC4162062  PMID: 23954845
adolescents; vaccination; information and communication technology (ICT); eHealth; Web 2.0; mHealth
9.  Epidemiology of tick-borne encephalitis (TBE) in Europe and its prevention by available vaccines 
Human Vaccines & Immunotherapeutics  2013;9(5):1163-1171.
Tick-borne Encephalitis (TBE), which is caused by a Flavivirus, is the most common tick-transmitted disease in Central and Eastern Europe and Russia. Today, TBE is endemic in 27 European countries, and has become an international public health problem. The epidemiology of TBE is changing owing to various factors, such as improvements in diagnosis and case reporting, increased recreational activities in areas populated by ticks, and changes in climatic conditions affecting tick habitats. Vaccination remains the most effective protective measure against TBE for people living in risk zones, occupationally exposed subjects and travelers to endemic areas. The vaccines currently in use are FSME-Immun®, Encepur®, EnceVir® and TBE vaccine Moscow®. The numerous studies performed on the efficacy and safety of these vaccines have shown a high level of immunogenicity and an excellent safety profile. Several studies have also shown a high level of cross-protection among strains belonging to different subtypes.
In the present paper we attempted to describe the continuously changing epidemiology of TBE in European States and to overview clinical development of available vaccines paying particular attention on cross-protection elicited by the vaccines.
PMCID: PMC3899155  PMID: 23377671
tick-borne encephalitis; epidemiology; prevention; TBE vaccines; vaccine cross-protection
10.  Influenza epidemiology in Italy two years after the 2009–2010 pandemic 
Since 2000, a sentinel surveillance of influenza, INFLUNET, exists in Italy. It is coordinated by the Ministry of Health and is divided into two parts; one of these is coordinated by the National Institute of Health (NIH), the other by the Inter-University Centre for Research on Influenza and other Transmissible Infections (CIRI-IT). The influenza surveillance system performs its activity from the 42nd week of each year (mid-October) to the 17th week of the following year (late April). Only during the pandemic season (2009/2010) did surveillance continue uninterruptedly. Sentinel physicians – about 1,200 general practitioners and independent pediatricians – send in weekly reports of cases of influenza-like illness (ILI) among their patients (over 2% of the population of Italy) to these centers.
In order to estimate the burden of pandemic and seasonal influenza, we examined the epidemiological data collected over the last 3 seasons (2009–2012). On the basis of the incidences of ILIs at different ages, we estimated that: 4,882,415; 5,519,917; and 4,660,601 cases occurred in Italy in 2009–2010, 2010–2011 and 2011–2012, respectively.
Considering the ILIs, the most part of cases occurred in < 14 y old subjects and especially in 5–14 y old individuals, about 30% and 21% of cases respectively during 2009–2010 and 2010–2011 influenza seasons. In 2011–2012, our evaluation was of about 4.7 million of cases, and as in the previous season, the peak of cases regarded subjects < 14 y (about 29%).
A/California/07/09 predominated in 2009–2010 and continued to circulate in 2010–2011. During 2010–2011 B/Brisbane/60/08 like viruses circulated and A/H3N2 influenza type was sporadically present. H3N2 (A/Perth/16/2009 and A/Victoria/361/2011) was the predominant influenza type-A virus that caused illness in the 2011–2012 season. Many strains of influenza viruses were present in the epidemiological scenario in 2009–2012.
In the period 2009–2012, overall vaccination coverage was low, never exceeding 20% of the Italian population. Among the elderly, coverage rates grew from 40% in 1999 to almost 70% in 2005–2006, but subsequently decreased, in spite of the pandemic; this trend reveals a slight, though constant, decline in compliance with vaccination.
Our data confirm that 2009 pandemics had had a spread particularly important in infants and schoolchildren, and this fact supports the strategy to vaccinate schoolchildren at least until 14 y of age. Furthermore, the low levels of vaccination coverage in Italy reveal the need to improve the catch-up of at-risk subjects during annual influenza vaccination campaigns, and, if possible, to extend free vaccination to at least all 50–64-y-old subjects.
Virologic and epidemiological surveillance remains critical for detection of evolving influenza viruses and to monitor the health and economic burden in all age class annually.
PMCID: PMC3891712  PMID: 23292210
coverage vaccination; epidemiology; influenza; influenza vaccine; influenza-like illness; pandemics
11.  Can Particulate Air Sampling Predict Microbial Load in Operating Theatres for Arthroplasty? 
PLoS ONE  2012;7(12):e52809.
Several studies have proposed that the microbiological quality of the air in operating theatres be indirectly evaluated by means of particle counting, a technique derived from industrial clean-room technology standards, using airborne particle concentration as an index of microbial contamination. However, the relationship between particle counting and microbiological sampling has rarely been evaluated and demonstrated in operating theatres. The aim of the present study was to determine whether particle counting could predict microbiological contamination of the air in an operating theatre during 95 surgical arthroplasty procedures. This investigation was carried out over a period of three months in 2010 in an orthopedic operating theatre devoted exclusively to prosthetic surgery. During each procedure, the bacterial contamination of the air was determined by means of active sampling; at the same time, airborne particulate contamination was assessed throughout the entire procedure. On considering the total number of surgical operations, the mean value of the total bacterial load in the center of the operating theatre proved to be 35 CFU/m3; the mean particle count was 4,194,569 no./m3 for particles of diameter ≥0.5 µm and 13,519 no./m3 for particles of diameter ≥5 µm. No significant differences emerged between the median values of the airborne microbial load recorded during the two types of procedure monitored. Particulates with a diameter of ≥0.5 µm were detected in statistically higher concentrations (p<0.001) during knee-replacement procedures. By contrast, particulates with a diameter of ≥5 µm displayed a statistically higher concentration during hip-replacement procedures (p<0.05). The results did not reveal any statistically significant correlation between microbial loads and particle counts for either of the particle diameters considered (≥0.5 µm and ≥5 µm). Consequently, microbiological monitoring remains the most suitable method of evaluating the quality of air in operating theatres.
PMCID: PMC3528722  PMID: 23285189
12.  Effectiveness of adjuvanted seasonal influenza vaccines (Inflexal V® and Fluad®) in preventing hospitalization for influenza and pneumonia in the elderly 
Annual vaccination is the main mean of preventing influenza in the elderly. In order to evaluate the effectiveness of the adjuvanted seasonal influenza vaccines available in Italy in preventing hospitalization for influenza and pneumonia, a matched case-control study was performed in elderly subjects during the 2010–2011 season in Genoa (Italy). Cases and controls were matched in a 1:1 ratio according to gender, age, socio-economic status and type of influenza vaccine. Vaccine effectiveness was calculated as IVE = [(1-OR)x100] and crude odds ratios were estimated through conditional logistic regression models. Adjusted odds ratios were estimated through multivariable logistic models.
In the study area, influenza activity was moderate in the 2010–2011 season, with optimal matching between circulating viruses and vaccine strains. We recruited 187 case-control pairs; 46.5% of cases and 79.1% of controls had been vaccinated. The adjuvanted influenza vaccines (Fluad® considered together with Inflexal V®) were associated with a significant reduction in the risk of hospitalization, their effectiveness being 94.8% (CI 77.1–98.8). Adjusted vaccine effectiveness was 95.2% (CI 62.8–99.4) and 87.8 (CI 0.0–98.9) for Inflexal V® and Fluad®, respectively. Both adjuvanted vaccines proved effective, although the results displayed statistical significance only for Inflexal V® (p = 0.004), while for Fluad® statistical significance was not reached (p = 0.09). Our study is the first to provide information on the effectiveness of Inflexal V® in terms of reducing hospitalizations for influenza or pneumonia in the elderly, and demonstrates that this vaccine yields a high degree of protection and that its use would generate considerable saving for the National Health Service.
PMCID: PMC3667930  PMID: 23143775
influenza; vaccines; adjuvanted vaccines; hospitalization; elderly
13.  Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies 
BMC Public Health  2012;12:623.
Human Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner’s sexual histories.
We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies.
We administered a questionnaire to students (14–24 years old) in five Italian cities.
7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9–56.7) and 52.5% of males (95% CI 50.5–54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.
With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms.
The results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.
These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.
PMCID: PMC3490840  PMID: 22871132
Sexual behaviour; Human papillomavirus; Adolescents; Young people; HPV vaccination; Sexually transmitted diseases (STDs)
14.  Meningococcal glycoconjugate vaccines 
Human Vaccines  2011;7(2):170-182.
Neisseria meningitidis is a major cause of invasive bacterial infections worldwide. For this reason, efforts to control the disease have been directed at optimizing meningococcal vaccines and implementing appropriate vaccination policies. In the past, plain polysaccharide vaccines containing purified capsular polysaccharides A, C, Y and W135 were developed, but failed to protect infants, who are at greatest risk.
Experience with the conjugate Haemophilus vaccine suggested that this approach might well empower meningococcal vaccines. Thus, a very efficacious vaccine against serogroup C Neisseria meningitidis was optimized and has been widely used in developed nations since 1999.
On the basis of epidemiological changes in the circulation of pathogenic serogroups in the United States, a quadrivalent conjugate vaccine against A, C, Y and W135 serogroups (Menactra™) has been developed and was approved by the US FDA (Food and Drug Administration) in 2005. Recently, another tetravalent conjugate meningococcal vaccine (Menveo™) has been licensed and made available in the United States of America and in the European Union.
Finally, in response to large epidemics caused by serogroup A meningococcus in Africa, a new, safe, immunogenic and affordable vaccine has been developed.
This review highlights the evolution of conjugate meningococcal vaccines in general and discusses how this kind of vaccine can contribute to preventing meningococcal disease.
PMCID: PMC3166476  PMID: 21178398
meningococcus; Neisseria meningitidis; glycoconjugate vaccines; meningococcal disease; immunity; vaccination
15.  A Heterologous MF59-Adjuvanted H5N1 Prepandemic Influenza Booster Vaccine Induces a Robust, Cross-Reactive Immune Response in Adults and the Elderly▿  
Clinical and Vaccine Immunology : CVI  2010;17(11):1817-1819.
Immunogenicity and safety of a booster dose of an MF59-adjuvanted H5N1 vaccine containing 7.5 μg A/turkey/Turkey/1/2005-like (clade 2.2) H5N1 hemagglutinin, given approximately 18 months after primary vaccination with a heterologous strain, were evaluated. The booster vaccine was well tolerated and induced a robust, cross-reactive immune response.
PMCID: PMC2976095  PMID: 20810680
16.  Randomized Trial on the Safety, Tolerability, and Immunogenicity of MenACWY-CRM, an Investigational Quadrivalent Meningococcal Glycoconjugate Vaccine, Administered Concomitantly with a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis Vaccine in Adolescents and Young Adults▿ †  
This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.
PMCID: PMC2849330  PMID: 20164251
18.  MF59®-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults 
PLoS ONE  2009;4(2):e4384.
Pathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.
Methods and Findings
Healthy adults aged 18–60 and >60 years (n = 313 and n = 173, respectively) were randomized (1∶1) to receive two primary and one booster injection of 7.5 μg or 15 μg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 μg and 15 μg doses were comparable. The rates for seroprotection (HI>40; SRH>25mm2; MN ≥40) after the primary vaccination ranged 72–87%. Six months after primary vaccination with the 7.5 μg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 μg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.
Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.
Trial Registration NCT00311480
PMCID: PMC2634740  PMID: 19197383
19.  Molecular Characterization of a New Variant of Rotavirus P[8]G9 Predominant in a Sentinel-Based Survey in Central Italy▿  
Journal of Clinical Microbiology  2006;45(3):1011-1015.
Rotavirus P[8]G9 was recognized as the most widespread genotype during a sentinel-based survey in Italy; phylogenetic analysis of the VP7 and VP4 genes showed that Italian isolates constituted a closely related genetic cluster distinct from the other G9 strains recently isolated in other European countries, America, and Asia.
PMCID: PMC1829138  PMID: 17166955
20.  Neutralizing and Hemagglutination-Inhibiting Activities of Antibodies Elicited by the 2004-2005 Influenza Vaccine against Drifted Viruses 
Clinical and Vaccine Immunology  2006;13(1):162-164.
Evaluation of the antibody responses induced by the 2004-2005 influenza vaccine strain against the homologous variant, the 2004-2005 field isolates, and a previous circulating strain showed that a correlation between neutralizing and hemagglutination-inhibiting activities exists only when the antigen is very close to the vaccine strain.
PMCID: PMC1356628  PMID: 16426017

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