Modelling the long-term persistence of neutralizing antibody in adults after one dose of live attenuated Japanese encephalitis chimeric virus vaccine.

In a study conducted in a non-endemic area, a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was found to provide 97% seroprotection at 6 months in JE-naive adults after 1 dose, and 87% of those protected at 6 months were still protected at 5 years. Because long-term seroprotection data are essential for decision-making on the need and timing of boosters, we applied statistical models to this dataset to predict individuals' neutralizing antibody titres and seroprotection up to 25 years post-vaccination. Three types of statistical model (linear, piecewise linear and exponential-type) with fixed and random effects were constructed to model antibody decline from the observed peak in antibody levels measured 28 days after vaccination. Individual seroprotection was based on the accepted threshold of 1:10 dilution units (antibody titre ≥10). The piecewise linear mixed model provided best fit amongst all tested models and identified 2 periods of antibody decline: an initial period of rapid decline followed by a period of much slower decline (50 times) starting on average 3.2 months (5th to 95th percentile range: 1.4-7.3) after vaccination. Predicted median antibody titres at 10 years were 38 (<10-174) and the corresponding seroprotection rate was 85.5% (72.7-94.9). The estimated median duration of seroprotection was 21.4 years (5th to 95th percentile range: 7.3-34.0). This analysis suggests that one dose of JE-CV confers to most adults a high level of protection against Japanese encephalitis for at least 10 years.

Predicted long-term persistence of pertussis antibodies in adolescents after an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine, based on mathematical modeling and 5-year observed data.

In a clinical trial, adolescents who had received a booster dose of reduced dose diphtheria-tetanus-5-component acellular pertussis vaccine (Adacel, Tdap) 5 years earlier maintained increased antibody concentrations to all antigens compared with pre-vaccination values. Observed data were applied to several mathematical models designed to predict further antibody decay for pertussis antigens. A linear mixed model including a random-intercept term provided the best fit for the observed data and was used for predictions. The predicted times for sufficient antibody decay to reach pre-vaccination levels were 15.3 years (95% CI: 7.0-28.0) for pertactin, 11.0 years (5.7-18.9) for fimbriae types 2 and 3, 10.5 years (3.6-24.7) for pertussis toxoid and 9.5 years (4.2-24.6) for filamentous hemagglutinin. For at least 87% of subjects, the 10-year predicted antibody concentration was higher than the limit of quantitation (LOQ) for each pertussis antigen measured. These results support Tdap booster doses every 10 years, following the current schedule for Td vaccination.

Aventis Pasteur vaccines containing inactivated hepatitis A virus: a compilation of immunogenicity data.

Inactivated hepatitis A vaccines were developed in the 1980s and were introduced during the early 1990s. The Aventis Pasteur (AvP) inactivated hepatitis A virus antigen is used in several different vaccine formulations licensed for adults and children. Presented here are the immunogenicity results compiled from 37 clinical trials performed in 20 different countries between 1991 and 2001 in which these vaccines were administered to adults (16 years of age and over), children (aged 12 months-17 years), and infants (younger than 12 months). The accumulated clinical experience with these hepatitis A virus-containing vaccines demonstrates the excellent immunogenicity of this antigen in a wide range of situations. As with other licensed inactivated hepatitis A vaccines, immunological priming is achieved in virtually all vaccinees after a single-dose primary immunization, and it may be reinforced by a booster vaccination administered 6-36 months after the primary vaccination.

Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant.

Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14, avidity increased between the ages of 7 and 12 months. After boosting at 12 months, avidity further increased for all serotypes. The adjuvant improved antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1 subclass, although some infants also produced IgG2 after boosting. In conclusion, the immunization of infants with this 11-valent pneumococcal conjugate vaccine increased avidity of IgG, suggesting successful immunologic priming.

Vaccination of immunocompetent elderly subjects with a live attenuated Oka strain of varicella zoster virus: a randomized, controlled, dose-response trial.

After primary infection in childhood, varicella zoster virus (VZV) remains latent in the dorsal route ganglia. Its reactivation later in life can lead to a zoster episode. VZV-specific, T-cell-mediated immunity (VZV-CMI) is likely to be important in preventing symptomatic reactivation. As CMI declines with age, a vaccine enhancing VZV-CMI might be effective in decreasing the incidence or severity of zoster in elderly subjects. A randomized, double blind controlled trial assessing CMI responses of elderly subjects immunized with a live attenuated, VZV-Oka vaccine was conducted. Two hundred healthy volunteers (55-75 years of age) received either a single injection of the VZV vaccine (PMC), containing 3200 (Oka 3200), 8500 (Oka 8500), or 41,650 (Oka 41650) PFU of live VZV, or a pneumococcus vaccine control group (Pneumo 23((R)). The immune response to VZV was assessed by measuring the T-cell response to VZV antigens, i.e. proliferation (stimulation index, SI), precursor cell frequency (PCF), cytokine secretion, and antibody titers. Six weeks post-vaccination, VZV-specific SI (adjusted mean values) was significantly greater (P<0.0001) in the 3 vaccine groups (with SI=5. 6 for Oka 3200; SI=5.0 for Oka 8500, and SI=7.2 for Oka 41,650) than in the control group (SI=2.9). The increase in PCF was striking, with 72.4, 91.2 and 85.1 precursors per million cells respectively in these 3 vaccine groups, vs 26.3 in the control group. No significant IL-4 secretion was observed in any subject, whereas the presence of IFN-gamma secretion was found to correlate with good responder status. The increase of these CMI parameters did not depend upon the titer of virus injected. Geometric mean titers of VZV antibodies increased in all vaccine groups and remained unchanged in the control group. Nevertheless, no correlation between the antibody response and the cell-mediated response was found. Live attenuated VZV vaccine caused a significant increase in VZV-CMI in a healthy, elderly population. No relationship between vaccine dose and the intensity of the specific response was found.

A dose-response study of a live attenuated varicella-zoster virus (Oka strain) vaccine administered to adults 55 years of age and older.

Decreased cell-mediated immune (CMI) response to varicella-zoster virus (VZV) is correlated with an increased risk of reactivation of latent virus from dorsal root sites, leading to herpes zoster. The cell-mediated and humoral immunogenicity of three concentrations (3200, 8500, and 41,650 pfu/dose) of a live attenuated VZV vaccine (Oka strain; VZV/Oka) was compared with a control pneumococcal polysaccharide vaccine in 200 healthy adults who were > or = 55 years old. Six weeks after vaccination, the VZV-specific CMI response (as measured by stimulation index values and precursor cell frequencies) was enhanced in all VZV/Oka vaccine groups compared with the control group (for all VZV/Oka groups combined vs. controls, tested with VZV crude antigen: stimulation index, P < .001; precursor cell frequency, P < .001). Geometric mean titers of anti-VZV antibodies increased in all VZV/Oka vaccine groups but remained unchanged in the control vaccine group. No dose effect of VZV/Oka vaccine was observed for CMI or humoral responses.

Clinical acceptability and immunogenicity of a pentavalent parenteral combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four- and six-month-old Chilean infants.

BACKGROUND: In recent years additional parenteral vaccines have been recommended for routine immunization of infants in the US and elsewhere. The ability to administer multiple vaccines as a single injection without unacceptably increasing reactogenicity or decreasing immunogenicity of any component would offer many practical advantages. METHODS: A randomized, open, controlled trial was conducted to assess the tolerance profile and immunogenicity, as well as to identify potential antigenic interferences, resulting from administration of a parenteral combination vaccine for infants. The vaccine contains diphtheria and tetanus toxoids, acellular pertussis antigens (DTaP), enhanced inactivated poliovirus (eIPV) and Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T). Infants (n=711) were randomly assigned to receive 1 of 5 regimens as the primary series at 2, 4 and 6 months of age, by group: (1) DTaP plus oral polio vaccine (OPV); (2) DTaP plus eIPV (separate injections); (3) DTaP-eIPV combined as a single injection; (4) DTaP-eIPV combined, plus a separate injection of PRP-T; or (5) DTaP-eIPV combined and reconstituting PRP-T, as a single injection. At 3, 5 and 7 months Groups 1, 2 and 3 received PRP-T. At 12 months all infants received a booster dose of DTaP reconstituting PRP-T as a single injection, plus a separate injection of measles, mumps and rubella vaccine. Groups 2, 3, 4 and 5 received OPV at 7 months, and all infants received OPV at 13 months. Serum immune responses were measured to the primary series at 2 and 7 months and to the booster dose at 12 and 13 months. RESULTS: Reaction rates were similar among groups. In the primary series combining eIPV with DTaP decreased geometric mean titers (GMTs) to diphtheria, tetanus and pertussis. In addition concomitant PRP-T (either simultaneous or combined) with DTaP-eIPV lowered anti-PRP and further decreased tetanus GMTs. Nonetheless in 100% of infants protective titers were achieved against diphtheria and tetanus (>0.01 IU/ml each) and against the poliovirus types 1, 2 and 3 after eIPV (Groups 2 to 5); 99% of infants (Groups 4 and 5) had protective titers against PRP (> or = 0.15 microg/ml). After boosting with DTaP/PRP-T decreased GMTs to diphtheria and PRP antigens were observed in the groups that received DTaP and eIPV combined. Nonetheless protective titers to diphtheria, tetanus and PRP occurred consistently. In contrast concomitant PRP-T with DTaP-eIPV enhanced the pertussis GMTs. CONCLUSIONS: We conclude that combined DTaP, eIPV and PRP-T in a single injection is well-tolerated and elicits an acceptable immune response to each component.

Immunogenicity of the recombinant GenHevac B Pasteur vaccine against hepatitis B in chronic uremic patients.

Immunogenicity of the recombinant GenHevac B vaccine (G), containing both the S and the preS2 antigen, was compared with that of the plasma-derived Hevac B (H) vaccine in 120 chronic uremic predialysis patients. Sixty received 20 micrograms/dose of G and 60 received 5 micrograms/dose of H at 0, 1, 2, 4, and 12 months. Two months after the fourth injection, seroconversion (antibody to hepatitis B surface antigen [HBs], > or = 2 mIU/mL) was seen in 85% of group G and 67% of group H patients (P < .02); seroprotection (anti-HBs, > or = 10 mIU/mL) was seen in 71% and 59%, respectively. The geometric mean titers (GMT) of anti-HBs in responders were 112 and 229 mIU/mL, respectively. After booster injection at month 12, seroconversion occurred in 94% and 76% and seroprotection in 84% and 70%, with anti-HBs GMTs of 879 and 1001 mIU/mL in groups G and H, respectively. The recombinant GenHevac B vaccine elicited seroconversion and seroprotection in a higher proportion of chronic uremic patients, with comparably high anti-HBs antibody titers in responders.

[Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity]. / Vaccin recombinant et vaccin d'extraction contre l'hépatite B chez l'insuffisant rénal: immunogénicité comparée.

OBJECTIVES: Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). METHODS: Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. RESULTS: Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. CONCLUSIONS: Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.