Christian Herzog

Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine.

Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold over 41 million doses worldwide of the virosomal adjuvanted influenza vaccine, Inflexal V. Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal V have been completed in which 3920 subjects participated. During its decade on the market, Inflexal V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and its purity is reflected in the low ovalbumin content. By mimicking natural infection, the vaccine is highly efficacious. Inflexal V is the only adjuvanted influenza vaccine licensed for all age groups and shows a good immunogenicity in both healthy and immunocompromised elderly, adults and children. This review presents and discusses the experience with Inflexal V during the past decade.

Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children.

Objective. To compare the immunogenicity and safety of a virosome-adjuvanted influenza vaccine (Inflexal V; Berna Biotech, Berne, Switzerland) and a split influenza vaccine (Fluarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) in children. Subjects and methods. The subjects, 453 children ages 6 to 71 months, were stratified into primed and unprimed and age groups (6 to 35 and 36 to 71 months) and then randomized 1:1 to receive virosome-adjuvanted (n = 224) or split influenza vaccine (n = 229), a half or full dose was given intramuscularly according to age. Unprimed children received a second dose after 4 weeks. Blood samples (n = 326) collected pre-and 28 days postvaccination were analyzed by hemagglutination inhibition test. Safety assessments were made at baseline and follow-up visits by the investigators and by parents for the 4 days after vaccinations. Results. Both vaccines induced an effective immune response. Seroconversion rates (>4-fold titer rise) against the WHO recommended strains A/New Caledonia (H3N2), A/Moscow (H1N1) and B/Hongkong (B) were 80.1, 66.0 and 90.4% for the virosome-adjuvanted and 75.9, 62.9 and 89.4% for the split influenza vaccine, respectively. Unprimed children’s seroconversion rates for H3N2 were significantly higher (P = 0.02) for the virosome-adjuvanted (88.8%) than for split influenza vaccine (77.5%). Seroprotection rates (titer of > 40) for H3N2, H1N1 and B, respectively, were 87.8, 80.1 and 90.4% after vaccination with the virosome-adjuvanted vaccine and 82.9, 78.2 and 89.4% after the split influenza vaccine. Unprimed children’s seroprotection rate was significantly higher (P = 0.03) for H3N2 after the virosome-adjuvanted (88.8%) than those for the split influenza vaccine (78.3%). Equivalent geometric mean titer fold increases were evident for both vaccines. No serious adverse events were seen. Pain/ tenderness, redness and swelling/induration was found in 25.4, 11.2 and 8.9% for the virosome-adjuvanted vaccine and in 24.0, 9.2 and 6.1% for the split influenza vaccine, respectively. The rates of fever, malaise/irritability and shivering was 6.3, 11.6 and 2.7% for the virosome-adjuvanted vaccine and 8.3, 11.8 and 2.6% for the split influenza vaccine, respectively. Conclusions. The virosome-adjuvanted influenza vaccine showed greater immunogenicity over the split influenza vaccine in unprimed children and showed a trend toward better immunogenicity in the rest of the study population. Both vaccines were well-tolerated.

Efficacy of Intranasal Virosomal Influenza Vaccine in the Prevention of Recurrent Acute Otitis Media in Children

To evaluate the efficacy of an intranasal, inactivated, virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media (AOM) in children with recurrent AOM, 133 children aged 1-5 years were randomized to receive the vaccine (n=67) or no vaccination (n=66). During a 6-month period, 24 (35.8%) vaccine recipients had 32 episodes of AOM; 42 (63.6%) control subjects had 64 episodes. The overall efficacy of vaccination in preventing AOM was 43.7% (95% confidence interval, 18.6-61.1; P=.002). Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season. The cumulative duration of middle ear effusion was significantly less in vaccinated children than in control subjects. Data suggest that the intranasal virosomal influenza vaccine might be considered among the options for the prevention of AOM in children <5 years old with recurrent AOM.

Reduced-dose intradermal vaccination against hepatitis A with an aluminum-free vaccine is immunogenic and can lower costs.

A reduced dose (0.1 mL) of intradermal hepatitis A virus (HAV) vaccine could facilitate the control of hepatitis A in countries of endemicity. All study subjects receiving an aluminum-free HAV vaccine intradermally were seroprotected 28 days after vaccination (anti-HAV titer, > or =10 mIU/mL). Seroprotection rates decreased to 80.8% at 12 months but returned to 100%, with titers increasing 28-fold, after receipt of a booster vaccination.

Evaluation of an Indirect Immunofluorescence Assay for Detection of Immunoglobulin M (IgM) and IgG Antibodies against Yellow Fever Virus

ABSTRACT The first commercial indirect immunofluorescence assay (IFA) using Euroimmun Biochip technology was evaluated for the serodiagnosis of immunoglobulin G (IgG) and IgM antibodies against yellow fever virus (YFV) and was compared with the plaque reduction neutralization test (PRNT), which is currently the gold standard test for YFV. An overall correlation between the tests of 98.7% was established based on the analysis of 150 sera from individuals after vaccination with the 17D yellow fever vaccine. The sensitivity and specificity, calculated using the 150 sera from vaccinees and 150 sera from healthy blood donors, were 95% and 95%, respectively, for the IgG IFA and 94% and 97% for the IgM IFA. Antibody titers found in the PRNT correlated poorly with the IgM and IgG titers detected by IFA. The analysis of preexisting heterologous flaviviral immunity revealed the presence of antibodies reactive with YFV, tick-borne encephalitis virus, West Nile virus, Japanese encephalitis virus, and dengue virus serotypes 1 to 4 in 20 out of the 150 vaccinees. The indirect IFA showed that nine of these individuals with previous flaviviral exposure who received 17D vaccine failed to produce detectable IgM antibodies. Despite this preexisting immunity, all vaccinees developed protective immunity as detected by PRNT and anti-YFV IgG antibodies as detected by IFA. The high specificity and sensitivity of the IFA make it a useful tool for rapid diagnosis of yellow fever during outbreaks, for epidemiological studies, and for serosurveillance after vaccination.

Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis a vaccine : A controlled trial in children aged 1-16 years

Background: The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. Methods: Subjects aged 1–16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (≥10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >−10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. Results: Mean age of 308 enrolled subjects was 8.9 years (range, 1.0–17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11–23 months, 2–4, 5–7, 8–10, 11–13, 14–16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. Conclusion: In children aged 1–16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.

Successful Booster Antibody Response up to 54 Months after Single Primary Vaccination with Virosome- Formulated, Aluminum-Free Hepatitis A Vaccine

This study demonstrates that a booster dose of the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal (Berna Biotech) is highly immunogenic in subjects who received a single primary dose of this vaccine 18-54 months earlier. There were no significant differences in geometric mean antibody titers (GMTs) among subjects who received the booster dose 18-29 months (GMT, 2330 mIU/mL), 30-41 months (GMT, 2395 mIU/mL), or 42-54 months (GMT, 2432 mIU/mL) after primary vaccination, indicating that delays in the administration of booster vaccination do not lead to a loss of immunogenicity.

Concomitant administration of a virosome-adjuvanted hepatitis a vaccine with routine childhood vaccines at age twelve to fifteen months: a randomized controlled trial.

Background: The objectives of this trial were to test for noninferiority of a virosomal hepatitis A virus (HAV) vaccine (Epaxal) coadministered with routine childhood vaccines compared with Epaxal given alone and to an alum-adjuvanted HAV vaccine (Havrix Junior) coadministered with routine childhood vaccines. Methods: Healthy children 12- to 15-month-old were randomized to receive either a pediatric dose (0.25 mL) of Epaxal coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 109; group A), or Epaxal given alone (n = 105; group B), or Havrix Junior coadministered with DTPaHibIPV, oral polio vaccine, and measles-mumps-rubella vaccine (n = 108; group C). A booster dose was given 6 months later. Anti-HAV antibodies were tested before and 1 month after each vaccination. Safety was assessed for 1 month after each vaccination. Solicited adverse events were assessed for 4 days after each vaccination. Results: HAV seroprotection rates (≥20 mIU/mL) at 1 and 6 months after first dose were: A: 94.2% and 87.5%, B: 92.6% and 80.0%, C: 78.2% and 71.3%, respectively (A versus C: P < 0.001 and P = 0.017 at month 1 and 6, respectively). The respective geometric mean concentrations were: A: 51 and 64 mIU/mL, B: 49 and 59 mIU/mL, C: 33 and 37 mIU/mL (A versus C: P < 0.001 at both time points). All groups achieved 100% seroprotection after the booster dose. The geometric mean concentrations after the booster dose were 1758, 1662, and 1414, for groups A, B and C, respectively (A versus C: P = 0.15). No clinically significant reduction in immune response to all concomitant vaccine antigens was seen. All vaccines were well tolerated. Conclusions: Coadministration of pediatric Epaxal with routine childhood vaccines showed immunogenicity and safety equal to Epaxal alone as well as to Havrix Junior. After first dose, Epaxal was significantly more immunogenic than Havrix Junior.