European Vaccine Research Articles

Immunogenicity of a reduced dose of A/H3N2 in the 2005 southern hemisphere formulation of inactivated split influenza vaccine

The 2005 southern hemisphere formulation of the inactivated split-virion influenza vaccine Vaxigrip unintentionally contained a lower concentration of haemagglutinin (HA) than European Pharmacopoeia (EP) and WHO specifications for one of the three strains. To evaluate the immunogenicity of the 2005 southern hemisphere formulation of an influenza vaccine containing 9 microg/dose of HA for A/Wellington/1/2004(H3N2) strain, and 15 microg/dose for each of the A/New Caledonia/20/99(H1N1) strain and B/Shanghai/361/2002-like strains. In an open, non-controlled multicentre clinical trial, 75 healthy adults (18-59 years) and 65 healthy older adults (> or =60 years) were vaccinated once. Serum samples were obtained on D0 and 21 for haemagglutination inhibition (HAI) antibody titration. A high proportion of adults (64%) and elderly (68%) were already seroprotected (HAI titre of > or =40) against A/Wellington/1/2004(H3N2) before vaccination, probably due to high circulation of an antigenically similar H3N2 strain and a high 2004 vaccination rate. By D21, seroprotection rates against H3N2 attained 93.8% and 96.0% in adults and elderly respectively. The other two immunogenicity criteria for annual licensure of influenza vaccines in Europe were also met in both age groups for the H3N2 strain, and also for the H1N1 and B strains. These results enabled the 2005 southern hemisphere vaccine to be used in expectation that it would provide satisfactory protection against influenza, despite the reduced H3N2 antigen content.

Rotavirus Vaccination in Europe: The Time Has Finally Arrived

Rotavirus Vaccination in Europe: The Time Has Finally Arrived

The old Edward Jenner and the new public health: the future of vaccines in Europe

‘Vaccination’, was the word that Jenner invented for his treatment against smallpox (from the Latin vacca , a cow), and so successful did his innovation prove that by 1840 the British government had banned alternative preventive treatments and the word was adopted by Pasteur for immunization against any disease. After clean water, vaccination is the most effective public health intervention in the world for saving lives and promoting good health but vaccines and vaccination are at a turning point. A number of new vaccines with major potential for controlling infectious diseases have just been licensed or are at advanced stages of development. Among the illnesses targeted are rotavirus diarrhoea, pneumococcal disease and cervical cancer (as caused by human papillomavirus), which together kill more than a … Correspondence: Walter Ricciardi, Department of Public Health, Catholic University of the Sacred Heart, Rome, Italy. e-mail: wricciardi{at}m.unicatt.it

Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January–October 2003

Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.

Gastroenteritis by rotavirus in Spanish children. Analysis of the disease burden

Rotavirus is one of the most common causes of gastroenteritis worldwide. With the commercialisation of effective rotavirus vaccines in Europe in sight, it is necessary to provide studies which evaluate the disease burden. The aim of this study is two-fold, on one hand, to determine the burden of the rotavirus disease in Spanish children under the age of five, and on the other, to estimate the economic cost of these hospitalizations. The study was undertaken during a 5 year period (2000-2004). The rotavirus hospitalization rate was determined using the Minimum Basic Data Set of the national hospital discharge register. The observed data were compared with those expected by applying a model developed by the Centers for Disease Control and Prevention (CDC) adapted for European Countries. The financial expense of these hospitalizations was estimated. Of all admissions coded as gastroenteritis, 31.6% were due to rotavirus. The hospitalization rate by rotavirus was 480 cases per 100,000 children under five. These data are within the confidence range proposed by the adapted CDC model. The financial expense due to hospitalizations reaches 123,262 euros yearly in a Spanish University Hospital. In conclusion, rotavirus contributes significantly to the hospitalization of acute gastroenteritis. The rate of hospitalization by rotavirus is higher compared to other studies carried out in Spain. In view of future commercialisation of rotavirus vaccines, more in-depth analysis considering direct and indirect costs are necessary.

Increasing Coverage and Efficiency of Measles, Mumps, and Rubella Vaccine and Introducing Universal Varicella Vaccination in Europe

Universal mass vaccination according to a 2-dose measles-mumps-rubella (MMR) vaccine schedule is recommended by the World Health Organization and is fundamental to the control of these important diseases. Very high coverage (first dose, > or =95%; second dose, > or =80%) is necessary to achieve and sustain high population immunity, and eventually interrupt indigenous transmission of these diseases. In 2006, the Advisory Committee on Immunization Practices issued a recommendation for 2 doses of varicella vaccine to be given universally to children. Coadministration of MMR and varicella vaccines, though efficacious and well tolerated, can be difficult because of the 2 separate injections and associated compliance issues. In addition to the general advantages of a combined vaccine, recently registered measles-mumps-rubella-varicella (MMRV) vaccines could facilitate introduction of varicella universal mass vaccination by simplifying administration and providing the potential to achieve high coverage rates for these 4 diseases.

How to optimise the coverage rate of infant and adult immunisations in Europe

BackgroundAlthough vaccination has been proved to be a safe, efficacious, and cost-effective intervention, immunisation rates remain suboptimal in many European countries, resulting in poor control of many vaccine-preventable diseases.DiscussionThe Summit of Independent European Vaccination Experts focused on the perception of vaccines and vaccination by the general public and healthcare professionals and discussed ways to improve vaccine uptake in Europe.Despite the substantial impact and importance of the media, healthcare professionals were identified as the main advocates for vaccination and the most important source of information about vaccines for the general public. Healthcare professionals should receive more support for their own education on vaccinology, have rapid access to up-to-date information on vaccines, and have easy access to consultation with experts regarding vaccination-related problems. Vaccine information systems should be set up to facilitate promotion of vaccination.SummaryEvery opportunity to administer vaccines should be used, and active reminder systems should be set up. A European vaccine awareness week should be established.

Canine leptospirosis infections – clinical signs and outcome with different suspectedLeptospiraserogroups (42 cases)

The aim of the study was to investigate the presence of serum antibodies to different Leptospira serogroups in dogs with a clinical diagnosis of leptospirosis in southern Germany and to compare seroreactivity to different serogroups with history, clinical signs, laboratory findings and survival rate. In this study, the data of 42 dogs with the diagnosis of leptospirosis were evaluated retrospectively. Dogs were presented to the Small Animal Medicine Teaching Hospital (Medizinische Kleintierklinik) of the Ludwig Maximilians University Munich, Germany, between 1990 to 2003. Reactivity to the serogroup grippotyphosa (13/42) was most frequently present, followed by reactivity to the serogroup saxkoebing (10/42). There was no difference in the clinical picture and the laboratory changes between dogs whose sera were reactive to different serogroups. Most of the dogs with leptospirosis in southern Germany had sera reacting to serogroups other than icterohaemorrhagiae and canicola, which are contained in the vaccine. Thus, currently available vaccines in Europe do not protect against the most common Leptospira organisms associated with clinical disease.

Immunogenicity and Reactogenicity of Two Recombinant Hepatitis B Vaccines in Small Infants: A Randomized, Double-Blind Comparative Study

Hepatitis B infection is very common in infants, especially in countries with limited resources. Hepatitis B vaccination is recommended in the routine immunization schedules in many countries, including India. We compared immunogenicity and reactogenicity of two recombinant hepatitis B (HB) vaccines in healthy infants. A total of 262 evaluable Indian infants received three doses of 10 microg of an Indian (GeneVac-B) or European (Engerix-B) HB vaccine in a double-blind, randomized fashion. The first dose, given at birth, was followed by a dose at age 6 and 14 weeks. All the subjects were initially seronegative for HB surface antigen (HBsAg) and anti-HB antibodies (anti-HBs). The post-vaccination anti-HBs titers were assessed by ELISA at the time of second and third dose, and 1 month after the third dose. Seroconversion and seroprotection were defined as anti-HBs titers > or =1 mIU/ml and > or =10 mIU/ml, respectively. After first dose, the seroconversion rates were 20% and 17%, in Indian and European vaccine recipients, respectively. The second and third dose increased the seroconversion to 84% and 80%, and to 98% and 98%, respectively. Correspondingly, the seroprotection rates after the first dose was 11% and 10%, and consequently 54% and 58%, and 97% and 95%. None of the differences between vaccines reached statistically significant proportions. Geometric Mean Titer after third dose was 383 mIU/ml and 285 mIU/ml, respectively, also this difference remaining insignificant. Adverse events were similar in both vaccine groups. Immunogenicity and reactogenicity of the Indian and European Hepatitis B vaccines were comparable, when immunization was started at birth.

Varicella vaccination in Europe: are we ready for a universal childhood programme?

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines

At the end of 2005, six European countries had implemented public immunization campaigns with serogroup C conjugate vaccines, and all had experienced substantial declines in the incidence of serogroup C disease. A quadrivalent ACWY meningococcal vaccine is in use in the USA, but serogroup A is extremely rare in Europe and serogroups Y and W135 are infrequent causes of disease. This paper outlines recommendations on the use of conjugate vaccines in Europe based on the experience with meningococcal C conjugate (MCC) vaccines so far.

Candidate HIV-1 Tat vaccine development: from basic science to clinical trials

Over the past 20 years most of the efforts in HIV vaccinedevelopment have focused on sterilizing immunity bytargeting the Envelope protein (Env). However, resultsfrom preclinical and clinical trials have been largelydisappointing [1–11]. Therefore, current vaccine strat-egies are not only aimed at preventing virus infection butalso at blocking virus replication and disease onset. Inparticular, the control of virus replication should provideprotection from disease development and reduce virustransmission, halting the HIV epidemic. This objectivemay be achieved by targeting virus regulatory genes,which are expressed early after infection, are essential forvirus replication and pathogenesis, and are moreconserved among HIV clades. This approach may beeffective for both preventive and therapeutic vaccinestrategies [12–68]. In this article we review thecharacteristics of Tat and why it was selected for use in avaccine.Wealsocitethelessonlearnedinthedevelopmentof this anti-Tat vaccine for use in human clinical trials.

Rotavirus vaccines: considerations for successful implementation in Europe

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.

Inactivated North American and European H5N2 avian influenza virus vaccines protect chickens from Asian H5N1 high pathogenicity avian influenza virus

High-pathogenicity (HP) avian influenza (AI) virus of the H5N1 subtype has caused an unprecedented epizootic in birds within nine Asian countries/regions since it was first reported in 1996. Vaccination has emerged as a tool for use in managing the infection in view of future eradication. This study was undertaken to determine whether two divergent H5N2 commercial vaccine strains, one based on a European and the other a North American low-pathogenicity AI virus, could protect chickens against a recent Asian H5N1 HPAI virus. The North American and European vaccine viruses had 84 and 91% deduced amino acid sequence similarity to the HA1 segment of haemagglutinin protein of Indonesia H5N1 HPAI challenge virus, respectively. Both vaccine strains provided complete protection from clinical signs and death. The vaccines reduced the number of chickens infected and shedding virus from the respiratory and intestinal tracts at the peak of virus replication. In addition, the quantity of virus shed was reduced by 10(4) to 10(5) median embryo infectious doses. The use of specific neuraminidase inhibition tests allowed identification of infected chickens within the vaccinated groups. These data indicate that the currently available H5 vaccines of European and North American lineages will protect chickens against the Asian H5N1 HPAI virus and reduce environmental contamination by the H5N1 HPAI virus. They will be an adjunct to biosecurity measures to reduce virus transmission.

Economics of Rotavirus Gastroenteritis and Vaccination in Europe

Rotavirus is a major cause of gastroenteritis in children throughout Europe and the world. In addition to causing morbidity and mortality in children, rotavirus gastroenteritis (RVGE) creates a major economic burden on health care systems and families in Europe. The costs of hospital admissions for RVGE and nosocomial infections generate significant medical treatment costs throughout the region. Less information is available on the costs associated with less severe episodes and the costs borne by families, including lost time from work. The availability of rotavirus vaccines presents an effective opportunity to prevent RVGE and these associated economic costs, as well as providing protection to each child and hence benefiting the child's family. The adoption of rotavirus vaccine by health authorities in Europe will require a comparison of the costs and benefits. Economic evaluations that compare the costs of vaccination to the economic benefits of rotavirus vaccination will provide an estimate of its financial impact on health care systems and society. However, to provide a complete picture, economic evaluations of rotavirus vaccines will need to account for both the reduced costs and the reduced morbidity from prevented RVGE. Cost-effectiveness analyses based on quality-adjusted life years (QALYs) provide a systematic approach for assessing vaccination as a health investment, comparing the incremental costs associated with rotavirus vaccination and the reduced morbidity and mortality. QALYs provide a standardized approach for quantifying and comparing reductions in health-related quality of life and premature mortality. Although methodologic limitations exist in applying the QALY approach to childhood vaccines, their use in cost effectiveness analyses allows decision makers to consider the full health benefits of rotavirus and other vaccines.

Clinical Trials of Rotavirus Vaccines in Europe

Clinical trials of a live oral candidate rotavirus vaccine were started in 1982 and soon demonstrated that severe rotavirus disease can be prevented by vaccination. The first bovine candidate vaccine was withdrawn because of inconsistent efficacy, and studies of a rhesus rotavirus vaccine were initiated. A field trial of rhesus-human reassortant tetravalent rotavirus vaccine in Finland was pivotal for the licensure of this vaccine (RotaShield) in the United States in 1998. However, this vaccine was withdrawn in 1999 because of association with intussusception. Safety therefore became a major issue in the development of new candidate rotavirus vaccines. A pentavalent bovine-human reassortant rotavirus vaccine (RotaTeq) showed about 70% efficacy against any rotavirus disease and 100% efficacy against severe disease in Finland, according to the Clark scale. A large, multinational safety trial indicated no association of this vaccine with intussusception, and its licensure is under review in the EU. An attenuated human rotavirus vaccine (RIX4414; Rotarix) was developed from G1 rotavirus strain 89-12. A trial in Finland showed efficacy comparable with that of RotaShield, and a larger trial is under way in several European countries. In the first epidemic season, vaccine efficacy was 73% against any and 90% against severe rotavirus (mostly G1) gastroenteritis, according to the Vesikari scale. A large scale safety trial, conducted in Latin America plus Finland, indicated no increased risk of intussusception among recipients of Rotarix compared with placebo. The licensure of Rotarix is in process in the European Union.

Phylogenetic analysis of ORF5 and ORF7 sequences of porcine reproductive and respiratory syndrome virus (PRRSV) from PRRS-positive Italian farms: A showcase for PRRSV epidemiology and its consequences on farm management

We investigated the dynamics of porcine reproductive and respiratory syndrome virus (PRRSV) variability in a range of swine PRRS-positive farms located in Northern Italy, to provide insights into the epidemiology and diffusion of the virus, particularly throughout the entire swine production chain. In this context, we also examined the effectiveness and the critical points of a recently developed gilts acclimatization program in swine breeder farms. To achieve these aims, we designed new primers and determined 64 complete open reading frame 5 (ORF5) sequences, representing Italian PRRSV field strains and the European vaccine Porcilis strain (Intervet); in addition, the more conserved ORF7 of 11 PRRSV strains were sequenced. The domains’ prediction of their putative protein sequences was performed as well. Based on these sequences, phylogenetic trees were inferred which revealed a high degree of variability among the PRRSV Italian strains. The outcomes of the phylogenetic analysis showed that the most frequent source of infection in PRRS-positive farms (sow herds, nursery sites, fattening units) was the introduction of animals carrying a new variant and not the modification of already present variants; moreover, the integration of data from phylogenetic analysis and from the clinical and serological status of the swine herds suggested that the acclimatization program could be a valid tool to stabilize the PRRS clinical picture in farms, only when applied in combination with rigorous bio-security routine management and avoid the incoming of new PRRSV variants.

Effects of two commercial European modified-live vaccines against porcine reproductive and respiratory syndrome viruses in pregnant gilts

The purpose of this study was to assess the effects of two currently available commercial European-type modified-live virus (MLV) vaccines against porcine reproductive and respiratory syndrome in a reproductive pig model. Sixteen 90-day pregnant gilts were divided into four groups and allocated to one of the following intranasal treatments: group A gilts served as negative controls; group B gilts were exposed to a virulent European field strain; group C gilts were exposed to vaccine strain VP046 Bis and group D gilts to vaccine strain All-183. The results indicated that MLV strains can replicate in breeding animals and have the ability to cross the placenta. In particular, viraemia was detected in all gilts in group C and 2/4 gilts in group D, at least at one time point. In addition, transplacental infection was demonstrated in 3/4 gilts in group C and 2/4 gilts in group D. However, congenital and early postnatal infection did not have a marked detrimental effect on piglet performance when compared to negative controls, and no statistically significant differences were observed in most cases. Conversely, the reproductive performance of gilts in group B was significantly worse than that of the other groups. Specifically, the number of born-alive piglets, the survival rate of piglets during lactation and the mean weight of weaned pigs were significantly lower. It was concluded that the two commercial European-type MLV vaccines tested had no marked detrimental effects in pregnant gilts, although the MLV strains can cross the placenta leading to the birth of congenitally infected piglets.

Pneumococcal vaccination policy in Europe.

Infection due to Streptococcus pneumoniae (Pneumococcus) (Pnc) is an important cause of invasive clinical manifestations such as meningitis, septicaemia and pneumonia, particularly in young children and the elderly. A 23-valent polysaccharide Pnc vaccine (PPV) has been available for many years and a 7-valent conjugate Pnc vaccine (PCV) has been licensed since 2001 in Europe. As part of a European Union (EU) funded project on pneumococcal disease (Pnc-EURO), a questionnaire was distributed to all 15 EU member states, Switzerland, Norway and the 10 accession countries in 2003 to ascertain current pneumococcal vaccination policy. Twenty three of the 27 target countries, constituting the current European Union (plus Norway and Switzerland), completed the questionnaire. PPV was licensed in 22 of the 23 responding countries and was in the official recommendations of 21. In all the 20/21 countries for which information was available, risk groups at higher risk of infection were targeted. The number of risk groups targeted ranged from one to 12. At least 17 countries recommend that PPV be administered to all those >65 years of age (in three countries, to those over 60 years of age). Thirteen countries had developed national recommendations for PCV in 2003. No country recommended mass infant immunisation at that time, but rather targeted specific risk groups (between 1 and 11), particularly children with asplenia (n=13) and HIV infection (n=12). PCV use was restricted to children under two years of age in seven countries, and in four countries to children under five years of age. Future decisions on use of pneumococcal vaccines in Europe will be decided on the basis of several factors including: local disease burden; the predicted impact of any universal programme, particularly the importance of serotype replacement and herd immunity (indirect protection to the unvaccinated population); the effectiveness of reduced dose schedules, and vaccine cost. Indeed, at least one country, Luxembourg, has since implemented a universal infant PCV immunisation policy.

Genetics and geographical variation of porcine reproductive and respiratory syndrome virus (PRRSV) in Thailand

The Thai isolates of porcine reproductive and respiratory syndrome virus (PRRSV) were obtained from the Chulalongkorn University-Veterinary Diagnostic Laboratory (CU-VDL). Virus isolation was confirmed by immunoperoxidase monolayer assay (IPMA) using SDOW-17. The virus genotype was determined using nested multiplex RT-PCR (nm RT-PCR) of ORF 1b. The nm RT-PCR was able to detect at least 10 TCID 50/ml of PRRSV. Of 137 Thai isolates, 66.42% belonged to the European (EU) genotype and 33.58% to the North American (US) genotype. ORF5 products of the eight US strains (00CS1, 01NP1, 01UD6, 02CB13, 02KK1, 02PB1, 02SP2 and 02SP3) and the six EU strains (01CB1, 01RB1, 02BR1, 02CB12, 02SB2 and 03RB1) were sequenced for genetic variation analysis. The US strains of the Thai isolates are clustered within the same group and are more closely related to the IAF-EXP91 from Canada (89–90% nucleotide identity), whereas the EU strains were very similar to the EU prototype, Lelystad virus (87–97.5% nucleotide identity). The ORF5 nucleotide identities within the US genotype tested in this study compared to the US prototype, VR-2332 varied from 83.7 to 85.2%, whereas 83.5–85.5% amino acid identities were found. Based on the phylogenetic tree, each pair of the Thai isolates (01NP1 and 02KK1, 00CS1 and 01UD6, and 01CB1 and 01RB1) was identical despite they were collected from different provinces. Therefore, there was no geographic influence on the spreading of PRRSV in Thailand. Interestingly, 02CB12 (EU genotype) shared over 99% similarity of the ORF5 nucleotide sequence and 98.6% of amino acid identity with the European vaccine, Porcillis ( AF378819). However, modified live virus vaccines for PRRSV have not yet been used in the swine population in Thailand. The results suggested that both US and EU genotypes exist in Thailand, genetic variation does occur in both genotypes, and the sources of the viruses appear to be from Canada and Northern Europe, respectively. In addition, the spreading of PRRSV in Thailand might be due to introducing infected replacement pigs or infected semen into the farm.