Portal de Periódicos da CAPES

ANTIBODY RESPONSES OF HEALTHY NEONATES TO TWO MIXED REGIMENS OF HEPATITIS B VACCINE

1999; Lippincott Williams & Wilkins; Volume: 18; Issue: 9 Linguagem: Inglês

10.1097/00006454-199909000-00025

1532-0987

Dexter S. Y. Seto, David J. West, Rebecca R. Gilliam, Virginia A. Ioli, David Ferrara, Beverly Rich,

Immunotherapy and Immune Responses

Since 1991 the Advisory Committee on Immunization Practices and the American Academy of Pediatrics (AAP) have recommended that all infants in the US be given a three dose course of hepatitis B vaccine.1, 2 The first dose can be given either shortly after birth (before hospital discharge) or at ∼2 months of age in conjunction with the initial doses of Haemophilus influenzae type b, polio, diphtheria, tetanus and pertussis vaccines. Two monovalent hepatitis B vaccines are licensed for use in the US (Engerix-B, SmithKline Beecham Pharmaceuticals; RECOMBIVAX HB, Merck & Co., Inc.).3, 4 Similar but non-identical processes are used in making the two vaccines.5 However, the active immunogen in both vaccines is a highly purified, alum-adsorbed complex of the S protein component of the hepatitis B virus surface antigen (HBsAg), that has been synthesized by a genetically recombinant strain of the yeast Saccharomyces cerevisiae. One of these hepatitis B vaccines is now also available in combined formulation with an H. influenzae type b vaccine (COMVAX, Merck & Co., Inc.).6 The combined vaccine is not indicated for use in newborns, but it may be given to infants who are at least 6 weeks of age.6 It is probable that the hepatitis B vaccine given to a newborn infant in the hospital will in many cases be from a different manufacturer than the one used by the pediatrician for the second and third doses in the series. The ACIP has stated that a mixed regimen of hepatitis B vaccines from different manufacturers is acceptable and can be expected to induce an immune response comparable with that obtained with vaccine from a single manufacturer.1 Our study sought to test that expectation by measuring the antibody responses of healthy infants to two mixed regimens of hepatitis B vaccine initiated with Engerix-B and completed with RE-COMBIVAX HB. Methods. The study was conducted at the Kapiolani Medical Center for Women and Children in Honolulu, HI, in accordance with a protocol prepared by the Merck Research Laboratories, West Point, PA. The study protocol and subject consent form were reviewed and approved by the Human Investigations Committee at the Center. Written informed consent was obtained from the parent or guardian of each infant enrolled in the study. The study was open to healthy neonates (≤ 7 days of age) born to noncarrier (HBsAg-negative) mothers and having a birth weight ≥2500 g. Subjects were assigned at random 1:1 to one of two mixed three dose regimens of hepatitis B vaccine. Those in one group (ERR) were given a dose of Engerix-B (10 μg/0.5 ml) within 7 days of birth, followed by doses of RECOMBIVAX HB (2.5 μg/0.5 ml) at 1 and 6 months of age; subjects in the other group (EER) were given Engerix-B within 7 days of birth and at 1 month of age, followed by a dose of RECOMBIVAX HB at 6 months of age. The postvaccination antibody titer to HBsAg (anti-HBs) in a blood sample taken at 7 months of age (1 month after the third dose of vaccine) was determined at the Merck Research Laboratories using the AUSAB radioimmunoassay test procedure (Abbott Laboratories). With this assay a sample: negative control counts ratio (S:N) of 2.1 signals a minimally detectable titer of anti-HBs. A somewhat higher anti-HBs titer of ≥10 mIU/ml of serum is considered to mark a protective response to vaccination, and multiple studies have shown that a course of hepatitis B vaccine typically induces such a response in >95% of healthy infants.1 Any child who failed to develop ≥10 mIU/ml after the three dose series was offered a fourth dose of vaccine. The hypothesis that ≥95% of vaccinated infants would have ≥10 mIU/ml of anti-HBs in a blood sample taken at 7 months of age (1 month after the third dose of vaccine) was to be tested by a one-sided one sample comparison (one for each treatment group) at the 0.05 significance level. With a targeted enrollment of 60 infants/group and an assumed evaluability of 85% (n = 51/group), if the true proportion with ≥10 mIU/ml of anti-HBs induced by one of the regimens was only 85%, then the study would have 80% power to discriminate from the hypothesized 95%. An observed proportion of 86% (44 of 51) or less would lead to rejection of the null hypothesis that the true proportion is 95%. Vaccine safety was monitored with report cards on which parents were asked to record the child's temperature, any injection site reaction or any systemic complaint on the day of each vaccination and daily for 5 days thereafter. Results and discussion. One hundred nineteen eligible neonates 0 to 4 days of age were enrolled in the study and randomized to vaccination with either the ERR (n = 60) or ERR (n = 59) regimen. Subjects in the ERR and EER treatment groups were similar in terms of gender (M:F ratio, 1.3 and 1.2), race (Asian 57 and 53%; mixed 40 and 42%; Caucasian 3 and 5%), and weight (mean, 7.1 and 7.3 lb). No child developed a serious adverse experience during the course of the study, and none withdrew from the study because of a vaccine-related adverse experience. Vaccination was generally well-tolerated, and the rates of adverse experiences appeared similar among infants in the two treatment groups. Injection site reactions were reported after 5% of the injections given to infants in the ERR group and after 7% of those in the EER group, whereas the proportions of injections followed by systemic complaints were 25 and 26%, respectively. The most common injection site reaction in either group was erythema, and irritability and sleepiness were the most common systemic complaints. One hundred nine of the children in the study received a full three dose series of vaccine. Of these 105 had a blood sample drawn and tested quantitatively for anti-HBs at ∼7 months of age (1 month after the third dose). Table 1 shows the proportion of vaccinees in each treatment group with any detectable anti-HBs, the proportion having an anti-HBs titer ≥10 mIU/ml and the overall geometric mean antibody titer. Responses to the two regimens were similar. Ninety-eight percent of the infants in the ERR group developed ≥10 mIU/ml anti-HBs with a geometric mean antibody titer of 587 mIU/ml, whereas responses in the EER group were 96% and 666 mIU/ml, respectively.TABLE 1: Anti-HBs responses at 7 months of age (1 month after the third dose of vaccine) One child in the study had no detectable antibody after vaccination, whereas two others developed a titer of <10 mIU/ml (individual titers of 3 and 9 mIU/ml). These children were each given a booster injection of RECOMBIVAX HB (2.5 μg/0.5 ml), and all subsequently developed anti-HBs titers ≥10 mIU/ml. We conclude from this study that a mixed vaccination regimen initiated with Engerix-B and completed using RECOMBIVAX HB can be expected to immunize successfully healthy infants, with ≥95% of the vaccinees developing a protective anti-HBs ≥10 mIU/ml. Dexter Seto, M.D. David J. West, Ph.D. Rebecca R. Gilliam, M.A. Virginia A. Ioli, B.A. David K. Ferrara, B.S. Beverly Rich, B.S. Kapiolani Medical Center for Women and Children Honolulu, HI (DS) Merck Research Laboratories West Point, PA (DJW, RRG, VAI, DKF, BR)