Francis André

Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines.

BACKGROUND In universal vaccination programs, when there is no postvaccination sero-1 logic assessment of response, there must be confidence that the vaccines used provide a high degree of seroprotection. OBJECTIVE This parallel analysis of 2 recombinant hepatitis B vaccines (Engerix B and Recombivax/HB-Vax II) was conducted to review the seroprotective efficacy of each vaccine in defined populations. METHODS Clinical studies of the 2 vaccines published as manuscripts or conference abstracts in the public domain between January 1986 and April 1999 were identified retrospectively by unrestricted screening of journals through BIOSIS, MEDLINE, and EMBASE and the Internet. Unpublished or internal company data were excluded to maintain impartiality. The studies were reviewed and analyzed. The studies were not assessed for quality other than a judgment of their eligibility for inclusion in the analysis. The primary outcome measure was the proportion of subjects in defined populations who showed an early seroprotective response to currently licensed vaccination schedules. Summary statistical analyses of seroprotective response rates and 95% CIs were calculated for each vaccine for each population. Seroprotective response was defined by an anti-hepatitis B surface antigen titer > or =10 IU/L measured between 1 and 3 months after the final vaccination. Because the study was designed specifically to review published immunogenicity data, safety data were not assessed. The study was not designed to demonstrate superiority of one vaccine over the other. RESULTS A total of 181 clinical studies representing 32,904 vaccinated subjects were reviewed and analyzed, of whom 24,277 had been vaccinated with Engerix B and 8627 vaccinated with Recombivax/ HB-Vax II. Seroprotection was achieved in 20,060 subjects (95.8%) with Engerix B and in 7774 subjects (94.3%) with Recombivax/HB-Vax II in the normal population vaccinated according to currently licensed 3-dose schedules. In a subgroup analysis, response rates in health care workers were 6492 subjects (94.5%) for Engerix B and 3245 subjects (92.2%) for Recombivax/HB-Vax II. Children and adolescents (1-19 years) showed the highest response rates to vaccination (4612 [98.6%], Engerix B; 2292 [98.9%], Recombivax/HB-Vax II). A total of 2875 infants (<1 year) (95.8%) achieved seroprotection with Engerix B; 701 (88.5%) achieved seroprotection with Recombivax/ HB-Vax II. CONCLUSIONS Hepatitis B vaccination programs using either Engerix B or Recombivax/HB-Vax II can achieve high seroprotective response rates, particularly in childhood and adolescence. Ideally, younger populations should be a primary target in current universal vaccination programs.

Safety and immunogenicity of hepatitis A vaccine in healthy children

The immunogenicity and reactogenicity of an inactivated hepatitis A (HA) vaccine in children were investigated. One hundred three healthy children who lacked antibody to HA virus (anti-HA virus), aged between 3 months and 6 years 8 months, were enrolled in this study. They received three doses of 360 enzyme-linked immunosorbent assay units of HA vaccine in a 0-, 1- and 6-month schedule. Blood tests for aminotransferase and anti-HA virus were performed 7 days before and 1, 6 and 7 months after the first dose. Anti-HA virus was tested by radioimmunoassay and also by enzyme immunoassay for titer determination. The seroconversion rates measured by enzyme immunoassay were 95.1% (98 of 103) at Month 1 and 100% at Months 6 and 7. Nine percent (28 of 309) of the injections were followed by local symptoms, usually mild soreness and swelling at the site of injection, and 12% (37 of 309) by minor general symptoms. We conclude that HA vaccine is highly immunogenic and safe in children. It may replace immunoglobulin as an effective method to prevent HA virus infection in children. We also suggest that the HA vaccine be administered to children in endemic areas.

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for influenza vaccination in children

BackgroundInfluenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza.DiscussionVaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases.SummaryCEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances.

Development and clinical testing of multivalent vaccines based on a diphtheria-tetanus-acellular pertussis vaccine: difficulties encountered and lessons learned.

The widespread use of whole-cell pertussis vaccines in the second half of the 20th century have reduced the incidence of the disease significantly. However, in some countries, concerns about the reactogenicity and potential neurological damage associated with whole-cell vaccines led to a decrease in vaccine acceptance and an increase in morbidity and mortality of pertussis in several countries. This prompted the development of less reactogenic acellular pertussis vaccines combined with diphtheria and tetanus toxoids, initially in Japan and later in other countries. In Europe, the improved diphtheria, tetanus and acellular pertussis (DTPa) vaccine was first introduced in March 1994. The pertussis component of this DTPa vaccine, developed by Glaxo SmithKline, consists of pertussis toxoid, filamentous haemagglutinin and pertactin. The vaccine is well tolerated, with a lower incidence of adverse reactions than after administration of whole-cell vaccines. The long-lasting efficacy and effectiveness of DTPa vaccines have been extensively documented and these are now the cornerstone of a large range of combined vaccines including DTPa-hepatitis B (HBV), DTPa-inactivated polio (IPV) and DTPa-HBV-IPV. A lyophilised Haemophilus influenzae type b (Hib) vaccine can be reconstituted with all of these liquid combinations. The introduction of well-tolerated and efficacious DTPa vaccines and their more polyvalent combinations has improved the acceptance and simplified the implementation of childhood immunisation. This paper is a review of the technical and scientific difficulties encountered and the lessons learned over the 10-year period that it took to develop and introduce six multivalent vaccines using the Glaxo SmithKline DTPa as a building block.

Immunogenicity of Twinrix in older adults: a critical analysis.

Twinrix™(GlaxoSmithKline Biologicals, Rixensart, Belgium) is the first combined vaccine to provide protection against both hepatitis A and B. This review presents a critical analysis of antibody responses stratified by age following vaccination with Twinrix in 264 adults aged above 40 years. A month after completion of a 0-, 1-, 6-month vaccination schedule with Twinrix, a good response was observed for both anti-HAV and anti-HBs serum antibodies, suggesting that is an effective vaccine in older adults.

Recommendations for tick-borne encephalitis vaccination from the Central European Vaccination Awareness Group (CEVAG).

Tick-borne encephalitis (TBE) is a viral neurological zoonotic disease transmitted to humans by ticks or by consumption of unpasteurized dairy products from infected cows, goats, or sheep. TBE is highly endemic in areas of Central and Eastern Europe and Russia where it is a major public health concern. However, it is difficult to diagnose TBE as clinical manifestations tend to be relatively nonspecific and a standardized case definition does not exist across the region. TBE is becoming more important in Europe due to the appearance of new endemic areas. Few Central European Vaccination Awareness Group (CEVAG) member countries have implemented universal vaccination programmes against TBE and vaccination coverage is not considered sufficient to control the disease. When implemented, immunization strategies only apply to risk groups under certain conditions, with no harmonized recommendations available to date across the region. Effective vaccination programmes are essential in preventing the burden of TBE. This review examines the current situation of TBE in CEVAG countries and contains recommendations for the vaccination of children and high-risk groups. For countries at very high risk of TBE infections, CEVAG strongly recommends the introduction of universal TBE vaccination in children > 1 y of age onwards. For countries with a very low risk of TBE, recommendations should only apply to those traveling to endemic areas. Overall, it is generally accepted that each country should be free to make its own decision based on regional epidemiological data and the vaccination calendar, although recommendations should be made, especially for those living in endemic areas.

Protective Efficacy of a Recombinant Deoxyribonucleic Acid Hepatitis B Vaccine in Institutionalized Mentally Handicapped Clients

Mentally handicapped clients in institutions are at high risk for hepatitis B virus (HBV) infection. In 1985, 770 mentally handicapped residents from four institutions in the Antwerp area were screened for HBV markers. The prevalence of hepatitis B surface antigen was 10.3 percent (range, 6.1 to 15.2 percent); 42.3 percent (range, 11.5 to 60.1 percent) had antibodies to hepatitis B surface antigen and the hepatitis B core antigen. In 1986, 275 seronegative mentally handicapped residents were vaccinated intramuscularly in the deltoid region with 20 micrograms (1.0 ml) of a recombinant deoxyribonucleic acid yeast-derived hepatitis B vaccine (Engerix-B, SmithKline Biologicals, Rixensart, Belgium) on a zero-, one-, six-month schedule. Serum samples were collected at Months 1, 2, 7, 12, and 24 and were tested for HBV markers by radioimmunoassay. The seroconversion rates for hepatitis B surface antigen antibodies were 39 percent at Month 1 (geometric mean concentration, 6.4 IU/liter), 82 percent at Month 2 (geometric mean concentration, 23.4 IU/liter), 97 percent at Month 7 (geometric mean concentration, 1,034 IU/liter), and 96 percent at Month 12 (geometric mean concentration, 269 IU/liter). Among the 214 residents evaluated at Month 12, 69 percent had hepatitis B surface antigen antibody levels greater than 100 IU/liter (geometric mean concentration, 603 IU/liter). No significant adverse reactions were observed. Within the first seven months of observation, HBV infection was detected in eight of 271 subjects (estimated annual incidence of 5 percent). During this period, none of the clients developed clinical hepatitis or showed biochemical evidence of liver damage. Between eight and 24 months, no additional HBV infections were detected. These data can be compared with an annual incidence of HBV infection of 8.7 percent in a historical cohort of mentally handicapped residents in one of the four institutions.

Rubella revisited: where are we on the road to disease elimination in Central Europe?

Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing. Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015. This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.

Safety and immunogenicity of hepatitis A vaccine in healthy adult volunteers

The immunogenicity and adverse reaction of an inactivated hepatitis A (HA) vaccine were investigated. Sixty healthy adult volunteers who lacked antibody to HA virus (anti‐HAV) received three doses of vaccine containing 720 enzyme‐linked immunosorbent assay (ELISA) units (EL.U) according to a 0, 1 and 6 month schedule. Blood tests for serum liver enzymes and anti‐HAV were performed at screening 7 days prior to, and 1, 6 and 7 months after the first dose. Anti‐HAV was tested by radio immunoassay and ELISA for titre determination. The seroconversion rates measured by ELISA were 98.3% (59/60) at months 1 and 6 and 100% at month 7. Sixty‐one per cent (109/180) of the documented injections were followed by local symptoms, essentially mild soreness at the site of injection; and 22.2% (40/180) by minor general symptoms including malaise, fatigue and lethargy. It is concluded that HA vaccine is highly immunogenic and safe. It may replace immunoglobulin as an effective method of preventing HA virus infection in adults.

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for 2009 pandemic influenza A(H1N1) vaccination.

The 2009 influenza A(H1N1) pandemic is markedly different from seasonal influenza with the disease affecting the younger population and a larger than expected number of severe or fatal cases has been seen in pregnant women, obese people and in people who were otherwise healthy. In Europe, influenza activity caused by the 2009 influenza A(H1N1) virus has passed the winter peak with nearly all countries now reporting lower influenza activity. However, although the rate of 2009 pandemic influenza A(H1N1) is declining, fatal cases continue to be reported and the future is hard to predict. The most effective protection against influenza is vaccination and increasing vaccine coverage is the only way to eliminate uncertainties regarding possible future waves of 2009 pandemic influenza A(H1N1). Recommendations have been developed for several central European countries but there is no clear or uniform definition with respect to priority groups or age groups who should receive vaccination. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of adults and children against 2009 pandemic influenza A(H1N1). CEVAG recommends vaccination of all health-care workers, pregnant women, children > or = 6 months and <2 years of age and people with chronic medical conditions as a first priority.