Search

Background: Vaccines against pandemic A/H1N1 influenza are required to protect the entire population. This dose range study aimed to identify priming antigen and adjuvant doses resulting in optimal levels of antibody-mediated protection after primary and one-year booster immunizations., Methods: This randomised trial enrolled 410 healthy adult (18-60 years) and 251 healthy elderly (>60 years) participants. Subjects received vaccine containing either 3.75 μg or 7.5 μg antigen, adjuvanted with half the standard dose, or a standard dose of MF59(®) (Novartis Vaccines) adjuvant, respectively. An additional adult cohort received non-adjuvanted vaccine containing 15 μg antigen. Two doses of investigational vaccine were administered three weeks apart, followed by a single booster dose of adjuvanted seasonal influenza vaccine one year after priming. Immunogenicity was assessed by haemagglutination inhibition and microneutralization assays pre- and post-immunization, the safety profile of each vaccine was also evaluated., Results: All of the vaccine formulations investigated were highly immunogenic and well tolerated in both adult and elderly subjects. The 7.5 μg formulation induced the highest antibody titres after primary and booster immunizations, and resulted in better long-term antibody persistence, in both age groups. Assessment according to European licensure criteria for influenza vaccines concluded that single adjuvanted priming doses containing 3.75 μg and 7.5 μg antigen were optimal for the adult and elderly populations, respectively., Conclusions: These data demonstrate that one priming dose of MF59-adjuvanted A/H1N1 vaccine provided healthy adult (3.75 μg or 7.5 μg formulations) and healthy elderly (7.5 μg formulation) individuals with adequate levels of seroprotection. Booster administration after two priming doses of either vaccine formulation resulted in the rapid development of seroprotective antibody titres., Trial Registration: www.clinicaltrials.gov (NCT00971906)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The potential consequences of an avian influenza pandemic warrants the development of safe, highly immunogenic pre-pandemic A/H5N1 vaccines with cross-clade protection. In this randomized, controlled study we compared the immunogenicity and safety of an MF59(®)-adjuvanted (Novartis Vaccines, Marburg, Germany) A/H5N1 pre-pandemic vaccine with that of a licensed, MF59-adjuvanted, seasonal influenza vaccine., Methods: Healthy adult (18-60 years, n=3372) and elderly (≥61 years, n=275) volunteers received either an initial dose of a licensed, non-adjuvanted, trivalent, seasonal influenza vaccine (Agrippal(®)) on Day 1, followed by one dose of MF59-H5N1 study vaccine on Day 22 and a second dose of MF59-H5N1 on Day 43, or alternatively, placebo on Day 1 followed by one dose of MF59-adjuvanted seasonal reference vaccine on Day 22 and a second dose of reference vaccine on Day 43. Homologous and cross-reactive A/H5N1 antibody responses were analysed by haemagglutination inhibition (HI), single radial haemolysis (SRH), and microneutralization (MN) assays three weeks after each vaccination. Vaccine safety was assessed throughout the study., Results: Analysis by HI assay found that two doses of MF59-H5N1 resulted in a seroconversion rate of 56% and a geometric mean ratio (GMR) of 7.1 in adult subjects. Similar results were observed on analysis by SRH (GMR 4.03; seroconversion 78% and seroprotection 91%) and MN (seroconversion 67%) assays. These data met the European licensure criteria for influenza vaccines. No significant difference in immunogenicity was detected between the adult and elderly populations. Anti-A/H5N1 cross-clade antibodies were detected by SRH, 49% of adult and 32% of elderly subjects achieved seroconversion after the second vaccine dose. Overall, MF59-H5N1 containing 7.5μg antigen was less reactogenic than the MF59-adjuvanted trivalent seasonal vaccine which contained 15μg antigen for each component strain., Conclusions: Two doses of MF59-H5N1 vaccine were well tolerated and induced adequate levels of seroprotection against homologous and cross-clade A/H5N1 virus. These data support the suitability of MF59-adjuvanted A/H5N1 vaccine for pre-pandemic use in adults and the elderly., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: The goal was to determine vaccination rates and predictors of vaccination behaviour of pediatricians in Munich, Germany., Methods: Standardised questionnaires were sent to all 133 office-based pediatricians in Munich., Results: 97 questionnaires (73%) were returned completely. Vaccination rates were sufficiently against diphtheria, tetanus, and poliomyelitis only. The other vaccinations recommended by the national immunisation advisory board (STIKO) were carried out to an insufficient extent. Vaccination rates of measles, mumps, and rubella were low. Parents' informed consent to STIKO's recommendations was the main determining factor of vaccination rates. Physicians' uncertainty in assessing contra-indications correctly was another important reason for insufficient vaccination rates., Conclusions: The health target of eliminating measles will not likely be reached. STIKO's recommendations as well as periodically vocational training courses, should be more compulsory to physicians. Self-responsibility of patients and parents should be raised by financial incentives on sick funds premiums.

Background Following vaccination with traditional smallpox vaccines or after exposure to vaccinated individuals, subjects with atopic dermatitis (AD) can develop eczema vaccinatum, a severe disease with disseminated eruption of pustular contagious lesions. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need. Methods An open-label controlled Phase I clinical trial was conducted to investigate the safety and immunogenicity of modified vaccinia Ankara (MVA) in 15 healthy subjects compared to 45 subjects with either mild allergic rhinitis, a history of AD or presenting with mild active AD. MVA was given (Week 0 and 4) by a subcutaneous injection during a 28-week observation period. Results No serious adverse event was reported and vaccinations with MVA did not lead to any clinically relevant skin reactions in AD subjects. Unsolicited administration site reactions did not show any trends compared to the healthy subject group. The majority of adverse reactions were mild to moderate, and all reactions were transient and resolved without intervention. The majority of vaccinees had seroconverted by ELISA (80–93%) and PRNT (69–79%) already two weeks after the first vaccination, increasing to 100% after the second immunization, with peak GMT above 1000 and 145 for ELISA and PRNT, respectively. Conclusions MVA was equally well tolerated and immunogenic in all enrolled subjects with mild to moderate pain and redness at the injection site being the most frequent adverse reactions. There were no differences in the safety or immunogenicity profile of MVA in healthy subjects or those with AD or allergic rhinitis. The study has confirmed MVA as a promising smallpox vaccine candidate and demonstrated in a small study population that the vaccine has a similar safety and immunogenicity profile in healthy subjects and people with active AD. Clinical trials registration: NCT00189917 . [ABSTRACT FROM AUTHOR]

Background Limited data exist on infectious diseases imported to various locations in Europe, particularly after travel within the continent. Methods To investigate travel-related disease relevant to Europe that is potentially preventable through pre-travel intervention, we analyzed the EuroTravNet database of 5,965 ill travelers reported by 16 centers in 'Western' Europe in 2011. Results There were 54 cases of vaccine-preventable disease, mostly hepatitis A ( n = 16), typhoid fever ( n = 11), and measles ( n = 8); 6 cases (including 3 measles cases) were associated with travel within 'Western' Europe. Malaria was the most commonly diagnosed infection ( n = 482, 8.1% of all travel-related morbidity). Among patients with malaria, the military most commonly received pre-travel advice (95%), followed by travelers for missionary, volunteer, research, or aid work (81%) but travelers visiting friends and relatives ( VFRs) were least likely to receive pre-travel advice (21%). The vast majority (96%) of malaria patients were resident in 'Western' Europe, but over half (56%) were born elsewhere. Other significant causes of morbidity, which could be reduced through advice and behavioral change, include Giardia ( n = 221, 3.7%), dengue ( n = 146, 2.4%), and schistosomiasis ( n = 131, 2.2%). Of 206 (3.5%) travelers with exposure in 'Western' Europe, 75% were tourists; the highest burden of disease was acute gastrointestinal infection (35% cases). Travel from 'Eastern' Europe ( n = 132, 2.2%) was largely associated with migration-related travel (53%); among chronic infectious diseases, tuberculosis was frequently diagnosed ( n = 20). Travelers VFRs contributed the largest group of malaria patients (46%), but also had the lowest documented rate of pre-travel health advice in this subset (20%). Overall, 44% of nonimmigrant ill travelers did not receive pre-travel advice. Conclusion There is a burden of infectious diseases in travelers attending European health centers that is potentially preventable through comprehensive pre-travel advice, chemoprophylaxis, and vaccination. Targeted interventions for high-risk groups such as travelers VFRs and migration-associated travelers are of particular importance. [ABSTRACT FROM AUTHOR]

Background: International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. Objective: To describe typical diseases in returned travelers accord-ing to region, travel reason, and patient demographic characteris-tics; describe the pattern of low-frequency travel-associated dis-eases; and refine key messages for care before and after travel. Design: Descriptive, using GeoSentinel records. Setting: 53 tropical or travel disease units in 24 countries. Patients: 42 173 ill returned travelers seen between 2007 and 2011. Measurements: Frequencies of demographic characteristics, regions visited, and illnesses reported. Results: Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quar-ters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologie (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. Limitations: Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. Conclusion: Many illnesses may have been preventable with ap-propriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. Primary Funding Source: Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

Persistence of immune response was assessed in adults aged >40 years ( N = 596) following primary vaccination with combined hepatitis A/B vaccine or concomitant monovalent hepatitis A and B vaccines. Anti-hepatitis A virus antibody responses persisted for at least 4 years regardless of the vaccine used, with anti-hepatitis B surface antibody responses higher and more sustained in subjects who received the combined hepatitis A/B vaccine. Response rates to an additional dose of the same vaccine(s) used for priming were high. [ABSTRACT FROM AUTHOR]

The article discusses the vaccination of travelers against Japanese encephalitis. The recommendations for Japanese encephalitis has been for high-risk circumstances but due to serious and fatal cases of Japanese encephalitis there has been a call for broader vaccine coverage. The vaccine against Japanese encephalitis was developed from a highly reactogenic mouse brain though there is another inactivated cell culture-derived vaccine. Vaccination against Japanese encephalitis should be recommended for repeat and long-term travelers to endemic areas of Asia.

Summary: Background: Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala. Methods: In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18–64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37·5 μg of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681. Findings: 2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3·7%, 95% CI 2·5–5·2) participants in the LT-patch group and 46 (5·6%, 4·1–7·4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34·6%, −2·2 to 58·9; p=0·0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p<0·0001). Serious adverse events occurred in 25 participants (14 in the LT-patch group and 11 in the placebo group), with all regarded as either unrelated or possibly related to treatment. Vaccine-induced hyperpigmentation persisted for at least 180 days after vaccination in 150 (18%) of the 849 participants who received both vaccinations and returned for final assessment in the LT-patch group, compared with none of the 842 participants in the placebo group. The vaccine was immunogenic, with a post-vaccination geometric mean titre of LT-specific serum immunoglobulin G of 3400·29, compared with 315·41 in the placebo group. Interpretation: Although the LT antigen was delivered effectively by the skin patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or other organisms. Future vaccines against travellers' diarrhoea might need to include several antigens against various diarrhoeal pathogens, and might need to be able to generate mucosal and higher systemic immunity. Funding: Intercell USA. [ABSTRACT FROM AUTHOR]

Summary: A multicentre, randomized, phase III clinical trial in 5071 healthy adults was conducted to evaluate the safety and reactogenicity of a 15μg HA dose of a candidate oil-in-water emulsion-based adjuvant system (AS)-adjuvanted split-virion H5N1 (AS-H5N1) vaccine compared to a licensed seasonal influenza vaccine, Fluarix™. 1 [1] Fluarix™ is a trademark of GlaxoSmithKline group of companies. Stringent criteria were used to evaluate adverse events and reactogenicity profile. Overall, 96.7% of the 5071 vaccinated subjects completed the study. Significantly more participants in the AS-H5N1 vaccine group reported general or local adverse events. Pain was the most common symptom in both treatment groups. Less than 1% of subjects withdrew from the study due to adverse events and no withdrawals were due to serious adverse events related to vaccination. The safety and reactogenicity profile of the AS-H5N1 candidate vaccine can be considered clinically acceptable in the context of its use against pandemic influenza. [Copyright &y& Elsevier]

Abstract: Challenged by contrasting data on low immune responses in the elderly with a combined hepatitis A/B vaccine, a randomised, controlled study was conducted to assess the immunogenicity of three hepatitis A and B vaccination regimens (group 1: combined hepatitis A/B vaccine Twinrix™ [GSK]; group 2: co-administered hepatitis A vaccine, Havrix™ [GSK]+hepatitis B vaccine Engerix™-B [GSK], group 3: co-administered hepatitis A vaccine, Vaqta™ [Sanofi-Pasteur MSD]+hepatitis B vaccine HB VAX PRO™ [Sanofi-Pasteur MSD]) and the effect of influencing factors in subjects >40 years. On completion of the full vaccination course, anti-HBs seroprotection (SP) rates were 92, 80 and 71% in groups 1, 2 and 3, respectively; anti-HAV seropositivity (S+) rates were 97, 99 and 99%, respectively. In group 1, anti-HBs SP rate was non-inferior as well as superior and anti-HAV S+ rate was non-inferior to that in groups 2 and 3. Anti-HBs response was most significantly influenced by the vaccine regimen, followed by age, gender and BMI (stepwise multiple regression analysis). BMI had the most significant influence on HAV response followed by age, gender and vaccine regimen. In conclusion, Twinrix™ induced superior hepatitis B SP rates and similar hepatitis A S+ rates compared to concomitant administration of monovalent vaccines in subjects aged >40 years. [Copyright &y& Elsevier]