Maria Paulke-Korinek

Universal mass vaccination against rotavirus gastroenteritis: impact on hospitalization rates in Austrian children.

Background: Since July 2007, rotavirus vaccinations have been subsidized in Austria for all children from the seventh week up to the sixth month of life. Vaccination coverage over the whole period was 72% with an increase to 87% in 2008. Methods: In a sentinel network including 11 pediatric hospital wards in Austria, data of children up to 15 years of age and hospitalized due to rotavirus gastroenteritis between January 2001 and December 2008 have been collected. Results: The hospitalization rates of children up to 12 months of age with rotavirus gastroenteritis were 2066 × 10−5 between 2001 and 2006 and decreased to 631 × 10−5 in 2008. For children between 12 and 24 months of age the hospitalization rate decreased from 1822 × 10−5 (2001–2006) to 1456 × 10−5 in 2008. In children aged 2 to less than 5 years, incidence rates were 436 ×10−5 (2001–2006) and 461 × 10−5 in 2008. In older children, the hospitalization rates remained unchanged. In the target population for the RV-vaccine, a decrease of hospitalization rates due to rotavirus gastroenteritis of 74% was observed compared to the era before the introduction of the vaccine. The field effectiveness of the vaccine was estimated between 61% and 98%, depending on assumptions about the vaccination status. Conclusions: Within 18 months, the universal mass vaccination program against rotavirus led to a substantial decrease in the hospitalization rates of the target cohort of the immunization program in Austria.

Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria

Austria was the first country in Europe implementing a universal mass vaccination program against rotavirus gastroenteritis (RV-GE) for all infants nationwide. Epidemiological data from a hospital based surveillance system show that incidence rates of children hospitalized with RV-GE decreased in 2009 compared to 2008 and compared to the prevaccination period 2001-2005. Decreasing hospitalization-rates from RV-GE were observed in children of all age groups, even in those not eligible for vaccination according to their age, suggesting herd immunity induced by universal mass vaccination against RV-GE. In 2009 the disease burden was highest in children below three months of age stressing the importance of the early start of the immunization course.

Sustained low hospitalization rates after four years of rotavirus mass vaccination in Austria.

This hospital based surveillance study evaluates the effects of the rotavirus mass vaccination program, which was initiated in Austria in August 2007. Since then, incidence rates of rotavirus hospitalizations in children <15 years of age have decreased by 70% and 64% in 2010 and 2011 compared to the pre-vaccination era (2001-2005). Incidence rates were highest in children <90 days of age, highlighting the importance of the early start of active rotavirus immunization. In children between 2 and 3.5 years in 2011, who were in the second and third year after vaccination in the universal mass vaccination program, incidence rates remained low suggesting sustained protection after vaccination up to three years. In the years 2010 and 2011, field effectiveness of the vaccines was between 79% and 96%, depending on the assumptions made for children without information on vaccination history. From genotyping an increase of the prevalence of G2P[4] in children with breakthrough infection (disease despite vaccination) can be suspected. The rate of severe adverse events was 1.3-1.5 per 10(-5) administered doses of rotavirus vaccines and no death, intussusception or Kawasaki disease was reported in 2010 and 2011 following rotavirus vaccination.

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial

BACKGROUND Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults. METHODS Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B. burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 μg, 60 μg, or 90 μg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347. FINDINGS 300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 μg, 51 to 60 μg, and 50 to 90 μg doses), and 149 to non-adjuvanted vaccines (50 to 30 μg, 49 to 60 μg, and 50 to 90 μg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41-0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13-0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 μg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4-20] of 50), injection-site pain (16 [32%, 21-45]), and tenderness (17 [34%, 23-47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17,321) and booster (19,056-32,824) immunisations. The 30 μg adjuvanted formulation induced the highest antibody titres after the booster: range 26,143 (95% CI 18,906-36,151) to 42,381 (31,288-57,407). INTERPRETATION The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin. FUNDING Baxter.

Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX®1440 in healthy subjects: A single-blind, randomized, controlled Phase 3 study

In travellers often several pre-departure immunizations are indicated, thus data are needed about possible interactions between vaccines. This Phase 3 study investigated the immunogenicity and safety of IC51 (JE vaccine) and HAVRIX1440 (hepatitis A vaccine) when administered alone or concomitantly to healthy subjects. The immune response was compared between single and concomitant vaccination in terms of geometric mean titre (GMT) and seroconversion rate (SCR) on Days 28 and 56. Immunogenicity was comparable for the 2 vaccines whether given together or separately which suggests that travellers to such regions could receive the vaccinations concomitantly.

Impact of a pertussis booster vaccination program in adolescents and adults on the epidemiology of pertussis in Austria

Background: A resurgence of pertussis has been observed in several countries; however, inconsistent data are available for Europe. In Austria, routine pertussis vaccination for babies is administered at 3, 4, and 5 months, and in the second year of life. Since 2002, regular boosters for all persons >6 years of age (including adults) are recommended. This study was undertaken to analyze epidemiologic trends of laboratory-reported pertussis to evaluate current vaccination strategy in Austria. Methods: Epidemiologic surveillance of laboratory-reported pertussis was conducted from January 1, 2000, to December 31, 2005. Infection was confirmed by positive serology, by positive culture of Bordetella pertussis, or by detection of sequences of the pertussis toxin gene by real-time polymerase chain reaction (RT-PCR). Data were assessed by age, hospitalization rate, seasonality, and incidence rate. Results: During the observation period 4395 reported cases of pertussis were eligible for analysis. The mean annual incidence increased from 6.4 per 100,000 population in 2000 to 11.1 cases per 100,000 population in 2005. Incidence rates were highest among children less than 1 year of age. Decreasing rates were observed for children and adolescents <16 years of age, whereas increasing rates were detected for persons 16 years of age and older. The mean age of reported pertussis cases increased from 30 years (±25.9 SD) in 2000 to approximately 44 years (±23.7 SD) in 2005. Hospitalization rates were highest in infants <6 months (86%) and lowest in those 10 to <50 years of age (17%), followed by an increase to 80% in persons 85 years of age and older. In general, no seasonal occurrence of disease was apparent. Conclusions: Pertussis incidence remains high among adults implying that coverage rates regarding booster vaccinations for adolescents and adults still are too low. Reinforced application of the current booster strategy is needed.

Long term immunity following a booster dose of the inactivated Japanese Encephalitis vaccine IXIARO®, IC51

INTRODUCTION IXIARO (IC51), a recently approved inactivated Japanese Encephalitis vaccine, is immunogenic and safe in a 0/28 days primary immunization schedule. Neutralizing antibody titers decline with time and booster doses are likely needed to enhance persistence of immunity. OBJECTIVES To assess the effect of a booster dose on neutralizing JE antibody titers for up to 12 months after boostering. METHODS In this phase III trial, 198 subjects, who had received primary immunization in a preceding randomized trial, were boosted with IXIARO 15 months after the primary immunization. Neutralizing antibody titers were assessed by plaque-reduction neutralisation test, PRNT. RESULTS Prior to the booster dose, 69.2% (137/198) of subjects had PRNT50 titers ≥ 1:10. One month after the booster, the rate of subjects with PRNT50 ≥ 1:10 (recognized as a protective titer) was 100%. This rate remained high at 98.5% at 6 and 12 months; GMTs were 22.5 before the booster and 900, 487 and 361 at 1, 6 and 12 months after the booster, respectively. CONCLUSION A booster dose of IXIARO at 15 months after primary immunization was highly immunogenic with GMTs >5-fold higher than those seen immediately after primary immunization, and remained at high levels for at least 12 months after the booster.

Vaccines and vaccination against tick-borne encephalitis

Tick-borne encephalitis (TBE) is an emerging viral zoonosis and is endemic from Japan, China, Mongolia and Russia, to Central Europe and France. There is no specific treatment and TBE can be fatal. The four licensed prophylactic vaccines are produced according to WHO manufacturing requirements. Large clinical trials and postmarketing surveillance demonstrated safety and efficacy of the two European vaccines. The two Russian vaccines showed their effectiveness in daily use, but limited published data are available on controlled clinical trials. Vaccination recommendations in endemic areas vary significantly. In some countries, public vaccination programs are implemented. The WHO has recently issued recommendations on evidence-based use of TBE vaccines. However, more data are needed regarding safety, efficacy and long-term protection after vaccination.

IC51 Japanese Encephalitis vaccine

Japanese encephalitis is the leading cause of viral encephalitis in Asia. Every year 30,000 – 50,000 cases and 10,000 deaths from Japanese encephalitis are reported, and underreporting has been suggested. No effective antiviral therapy exists to treat this mosquito-borne flavivirus infection. For active immunization vaccines are available. The manufacturing of the only vaccine that was internationally licensed, JE-VAX®, was ceased in 2005. Therefore a shortage of Japanese encephalitis vaccines might occur before new generation vaccines based on cell culture technology will be available. A promising new vaccine candidate is the inactivated whole-virus vaccine IXIARO® (Strain SA14-14-2), developed by Intercell AG. Which was licensed in Europe, the USA and Australia in spring 2009. Recently, successful Phase III immunogenicity and tolerability studies were published, indicating that this vaccine will be an acceptable approach to active immunization against Japanese encephalitis. Cell-culture-based vaccines will not only be used in the population living in endemic areas where the risk of infection is high, but also by travelers and military personnel.

Factors associated with seroimmunity against tick borne encephalitis virus 10 years after booster vaccination

In a sample of originally 430 healthy adults (18-84 years of age) with documented basic and booster immunization against tick borne encephalitis, cumulative seroprotection rates 8 (n=178) and 10 years (n=183) after the last booster dose were 86.8% and 77.3% according to the neutralization test, respectively. In subjects aged 50 years and older, antibody titers were significantly lower compared to subjects younger than 50 years. History of any allergy but not previous exposure to other flaviviral antigens was associated with higher neutralization titers. In subjects with waning immunity, a single booster dose induced a strong anamnestic antibody response.