F. Ambrosch

Immunogenicity and protectivity of a new liposomal hepatitis A vaccine.

In this study we investigated a new liposomal hepatitis A vaccine (Epaxal) developed by the Swiss Serum and Vaccine Institute clinically and immunologically using a one dose priming schedule and a booster injection after 1 year. This vaccine contains formalin inactivated hepatitis A virus particles attached to phospholipid vesicles together with influenza virus haemagglutinin. Two doses of the vaccine were administered at months 0 and 12 in 117 volunteers. Blood samples were drawn at days-7, 14 and 28 and after 6, 12 and 13 months, local and systemic reactions were monitored by means of questionnaires. Immunogenicity was evaluated as usual by the determination of anti-HAV from the collected sera using the ELISA technique. In order to evaluate the protective efficacy of the vaccine induced antibodies a sample of 25 sera mainly from vaccinees showing low ELISA titres was additionally analysed by means of a virus NT. The vaccine was excellently tolerable and highly immunogenic. Seroconversion evaluated by ELISA was 97 and 99%, respectively, 14 and 28 days after the first dose and 100% after the second dose. NT titres were well correlated with ELISA titres and showed similar seroconversion rates even in the early phase of immunization. The results of this study show that with two doses of the liposomal hepatitis A vaccine administered at months 0 and 12 early protection within 14 days and long lasting immunity can be achieved.

Influenza vaccination in 22 developed countries: An update to 1995

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.

Safety and immunogenicity of an inactivated hepatitis A candidate vaccine in healthy adult volunteers

The reactogenicity and immunogenicity of a formaldehyde-inactivated hepatitis A vaccine have been investigated. Three different dose levels of vaccine (180, 360 and 720 ELISA units) were administered to healthy volunteers according to a 0, 1, 2 and 12 month schedule. The vaccine was safe and well tolerated. Reactions observed following vaccination were essentially mild and were not dependent upon the quantity of antigen administered. All subjects had measurable titres of anti-HAV antibodies after the full vaccination course; the immune response to the vaccine was dose-related. Antibody titres in vaccinees at month 13 were between 60- and 190-fold higher than those observed in a group of subjects given anti-HAV immunoglobulin.

Influenza Vaccination in 29 Countries An Update to 1997

AbstractObjective: This report updates for 1996 and 1997 our 2 earlier reports on the use of influenza vaccination in various countries. Methods: Methods for obtaining information on influenza vaccine use from 1980 to 1995 in each country are described in our earlier reports. The current report includes data for 29 countries. Results: Among 16 countries of Western Europe, vaccine use increased substantially in The Netherlands, Finland (1996) and in Ireland (1997). In the remaining 13 countries, vaccine use increased somewhat or remained the same. In the US, vaccine use increased steadily throughout the 1990s, reaching a level of 281 doses per 1000 population in 1997. In New Zealand, there was a substantial increase in 1997, while vaccine use remained relatively unchanged in Canada, Australia and Korea. In Japan and Singapore, little or no influenza vaccine was used. In 1997, 6 countries in Central Europe used modest amounts of influenza vaccine. Among all 29 countries, in 1997 all but 3 (the UK, Ireland and Denmark) had age-based recommendations for influenza vaccination. This changed in 1998 when the UK and Denmark recommended vaccination for persons ≥75 years and ≥65 years of age, respectively. Ireland is considering an age-based recommendation. Many countries provide reimbursement for influenza vaccination through national or social health insurance, at least for some recommended groups. In virtually all countries, however, many persons pay for vaccination themselves. The levels of vaccine use in different countries are not related to per capita healthcare spending. Instead, they reflect different levels of awareness of influenza as an important disease and the effectiveness of vaccination in its prevention. Conclusions: Influenza vaccination has continued to increase or has stabilised in most developed countries, and vaccine is also being used in several developing countries. In spite of much progress, however, the full benefits of influenza vaccination have yet to be achieved in any country.

A hepatitis B vaccine formulated with a novel adjuvant system.

Although more than 95% of the vaccinated population responds to the currently licensed vaccines against hepatitis B, some groups were found to be low responders. Lipid A as adjuvant, through its ability to activate macrophages, might improve humoral as well as cellular immune response. Therefore we evaluated the profile of a hepatitis B vaccine with the new adjuvant system SBAS4. 150 young adults were enrolled and randomized into three groups: one received the SBAS4 hepatitis B vaccine, the second Engerix-B(TM) and the third a hepatitis B vaccine with an alternative formulation on alum. Vaccinations were at 0 and 6 months. The vaccine was well tolerated. At month 7 all vaccinees were protected but with significant differences in GMTs between groups: 13,271 mIU/ml for the SBAS4 group versus 1203 and 1823 mIU/ml. Hence the hepatitis B vaccine with the new adjuvant system is more immunogenic compared to the other vaccines containing the same antigen and could be suitable for a two dose schedule.

Inactivated hepatitis A vaccine: long-term antibody persistence

During the clinical development of safe, well tolerated and immunogenic vaccines against hepatitis A the persistence of protective antibodies was estimated, based on relatively short observation periods of 18 months to 3 years. We report here on longterm persistence of antibodies in volunteers who participated in one of the early clinical trials on inactivated hepatitis A candidate vaccines. In a randomized trial three groups of altogether 110 healthy adults, initially hepatitis A virus (HAV) seronegative persons were vaccinated with an inactivated hepatitis A vaccine according to the schedule 0-1-2-12 months. One group received 180 ELISA units, one group 360, and one 720 ELISA units per dose. Blood samples were taken prior to the first vaccination and at months 1, 2, 3, 4, 6, 12, 13, 18, 24, 36 and 84. The decrease of antibodies was characterized by two disappearance rates: a rapidly decreasing component and a slower decreasing one becoming predominant ca 12 months after booster vaccination. The disappearance of antibodies could be described by a two-component model which holds for t > or = 13 months. The estimated disappearance rates for the slow component (annual decrease) was found to be 11 and 13% for the 180 and 360 El. U groups, respectively (the 720 El. U group showed no decline, which was probably due to the small sample size). The estimated persistence of antibodies within protective range varied between 24 and 47 years depending on individual titres reached at month 13 and vaccination dose.

Simultaneous vaccination against hepatitis A and B: results of a controlled study.

Hepatitis A and hepatitis B are endemic in many countries and must be considered as serious health risks for large parts of the world population. Simultaneous or combined vaccination against these two diseases would therefore be most advantageous. In order to investigate possible interactions between these vaccines with respect to their tolerability and immunogenicity, we conducted a randomized prospective study comparing single and simultaneous administration of the two vaccines. Three groups of healthy volunteers, each with 55 persons, were included in the study. All were negative for hepatitis A and hepatitis B markers and had normal serum liver enzyme values. Group I received hepatitis A vaccine (720 ELISA units) into the left deltoid muscle, group II received hepatitis B vaccine (20 micrograms) into the right deltoid muscle and group III received hepatitis A vaccine into the left, and hepatitis B vaccine into the right deltoid muscle. Three doses of the vaccines were administered at 0, 1 and 6 months. Local and systemic reactions were monitored by means of questionnaires. Blood samples for determination of antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen (anti-HBs) and of serum SGOT and SGPT levels were drawn at months 0, 1, 2, 6 and 7. There were no serious general and only mild local reactions. The mean serum SGOT and SGPT values remained in the normal range in all groups. The seroconversion rates and mean geometric titres of the anti-HAV and anti-HBs antibodies were similar when the vaccines were administered separately or simultaneously. There were no significant differences between the compared groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of vaccine-induced antibody to hepatitis A virus

A level of 10 mIU hepatitis A antibodies/ml as measured by ELISA is believed to be the minimal protective concentration. If this level is considered, the mean persistence of vaccine induced antibodies is approximately 10-11 years after booster dose, 6-7 years if only the primary doses are given and 5-6 years if the minimal individual titre is taken into account.

Estimated persistence of anti-HAV antibodies after single dose and booster hepatitis A vaccination (0-6 schedule)

The persistence of antibodies after a single dose and booster vaccination against hepatitis A (Havrix 1440) has not yet been assessed. By reanalysing previously published data of serum titres and application of a two-component model, we estimated the duration of protection. In 134 vaccinees, aged 20-39 years, the GMT 1 month after booster was 3629 mlU/ml, which would result in an estimated duration of protection of 34.5 years and in 66 vaccinees aged 40-62 years a GMT of 2320 mlU/ml was calculated, resulting in a duration of protection of 31.5 years. Even when taking the minimum observed titres in the older age group into account, the duration of protection will be more than 10 years. Considering at the same time, its good tolerability and compliance, the single dose hepatitis A vaccination appears highly recommendable in travel medicine.

Combined vaccination against yellow fever and typhoid fever: a comparative trial

In order to evaluate a combination of yellow fever and typhoid fever vaccine, we conducted a controlled trial comparing reactogenicity and immunogenicity of Vi polysaccharide (ViPS) vaccine and yellow fever 17D (YF) vaccine after single, simultaneous and combined administration. The combined YF/ViPS vaccine was prepared by using the liquid ViPS vaccine as a diluent for the YF vaccine. The stability of such a reconstitution had been assessed in vitro. Safety was evaluated using a self-surveillance form and by repeated clinical visits. Immunogenicity was evaluated by a plaque reduction test for YF and by radioimmunoassay for ViPS. Tolerability was satisfactory in all groups. There was no increase in local or general reactions in groups receiving both vaccines, whether given simultaneously or combined. The serological response to ViPS was similar after single and simultaneous or combined administration. Interestingly, the immune response to YF was significantly enhanced in groups receiving the vaccines simultaneously or combined, suggesting a potential adjuvant effect of ViPS.