Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine.

The immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) was evaluated using US veterinary medical students. In the first study, 242 healthy adults were enrolled in a randomized, modified double-blind, multicenter trial and received five doses of either CPRV or human diploid cell vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28 concurrently with human rabies immunoglobulin in a simulated post-exposure prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached 0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all subjects in both vaccine groups by day 14 and remained above that level through day 90. In the second study, 438 healthy adults were enrolled in a randomized, double-blind, multicenter trial and assigned to receive five doses from one of three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post-immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all subjects and remained above that level through day 42 when the study was terminated. The three lots were considered equivalent. The percentage of subjects with at least one local reaction during the five-dose regimen was slightly lower in the CPRV group than in the HDCV group (P=0.06). The most frequently reported local reaction for all doses of vaccine was pain at the injection site. Headache, myalgia, and malaise were the most frequently reported systemic events. The percentage of subjects with at least one systemic event was significantly lower for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in these studies. The results of these studies indicate that CPRV administered intramuscularly to healthy adults is immunogenic and is associated with fewer local and systemic reactions than HDCV.

Choosing a route of administration for quadrivalent meningococcal polysaccharide vaccine: intramuscular versus subcutaneous.

A clinical trial was conducted to compare intramuscular (im) with subcutaneous (sc) routes for administration of quadrivalent meningococcal polysaccharide vaccine in 141 adults. Safety assessment showed the im route had reduced erythema (P<.01) and reduced headache on days 1 and 2 (P<.05). Serological testing for serum bactericidal antibody titers against capsular groups A and C did not detect significant differences.

Comparison of the safety and immunogenicity of acellular (BIKEN) and whole-cell pertussis vaccines in 15- to 20-month-old children.

OBJECTIVE: To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine (BIKEN) with whole-cell diphtheria and tetanus toxoids and pertussis vaccine (WC-DTP) when administered to children aged 15 to 20 months. DESIGN: A randomized, double-blind study. SETTING: Children in this study were from 12 general pediatric practices (11 were private and one was university-affiliated) and one inner-city university pediatric clinic. PARTICIPANTS: Two hundred forty-six children aged 15 to 20 months who had received a three-dose primary series of standard WC-DTP vaccine during infancy. SELECTION PROCEDURES: Children were randomly assigned to receive either WC-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (DT-aP) in a 1:3 ratio at the 11 private practices and in a 1:1 ratio at the university-affiliated practice and inner-city university pediatric clinic. INTERVENTIONS: The DT-aP vaccines contained 23.4 micrograms each of pertussis toxin and filamentous hemagglutinin per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as WC-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions at 6, 24, 48, and 72 hours were recorded by parents who were contacted by telephone at 24 and 72 hours and 14 days after immunization. MEASUREMENTS/MAIN RESULTS: An indirect enzyme-linked immunosorbent assay method was used to determine IgG antibody response to pertussis toxin and filamentous hemagglutinin and IgG, IgA, and IgM to tetanus toxoids; a Chinese hamster ovary cell assay was used to measure functional antibodies to pertussis toxin; serum neutralization on VERO cells assayed diphtheria anti-toxin. Recipients of the DT-aP vaccine had fewer local reactions in the first 6 to 48 hours and fewer systemic reactions at 24 hours than did recipients of the WC-DTP vaccine. Acetaminophen was administered to 31% of DT-aP recipients compared with 63% of WC-DTP recipients. Infants given DT-aP had higher geometric mean antibody titer levels against pertussis antigens after vaccination. CONCLUSION: The BIKEN DT-aP vaccine used in this study is less reactogenic and more immunogenic for selected pertussis antigens than the WC-DTP vaccine in children aged 15 to 20 months.

Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group.

OBJECTIVE: --Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children. The reasons why the vaccination fails in some children are unknown. This study investigated host factors in children who developed the disease despite conjugate vaccination. DESIGN, PATIENTS, OUTCOME MEASURES:--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease. We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide. The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease. RESULTS: --Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval [CI], 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001). With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses. The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients. CONCLUSIONS: --In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1. However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency.

Depression of anticapsular antibody after immunization with Haemophilus influenzae type b polysaccharide-diphtheria conjugate vaccine.

Invasive Haemophilus influenzae type b infections have been observed in the week after immunization with capsular polysaccharide vaccine. We sought to document depression of antibody concentrations after immunization of 18-month-old infants with H. influenzae type b capsular polysaccharide-diphtheria conjugate vaccine. All 9 infants with detectable preimmunization anticapsular antibody had depression of antibody concentrations on the second day after immunization (P = 0.002). By Day 7 all had achieved anticapsular antibody concentrations greater than 0.15 micrograms/ml, a level believed to provide protection to immediate challenge with H. influenzae type b. Of those without detectable preimmunization antibody, 7 of 21 (33%; 95% confidence interval, 11 to 56%) had not achieved concentrations of greater than 0.15 mg/ml 1 week after immunization. We conclude that there is depression of anticapsular antibody concentrations during the first week after immunization with H. influenzae type b capsular polysaccharide-diphtheria conjugate vaccine. We speculate that H. influenzae type b infections after immunization with H. influenzae type b vaccines may be the result of: (1) low antibody concentrations because of either depression of antibody concentrations or failure to develop antibody; and (2) exposure to H. influenzae type b. Depression of antibody concentrations could be explained by binding of in vivo antibody to the vaccine.