中国婴幼儿接种吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗的安全性和免疫原性研究

目的 比较吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTaP-IPV//PRP～T联合疫苗)与吸附无细胞百白破联合疫苗(DTaP)、b型流感嗜血杆菌结合疫苗(Hib结合疫苗)、注射用灭活脊髓灰质炎疫苗(IPV)的免疫原性和安全性.方法 受试者随机分为三组.试验组(A组和B组)分别于2、3、4月龄...     

Immune response to a diphtheria and tetanus toxoid administration in a three-dose diphtheria tetanus whole-cell pertussis/enhanced inactivated poliovirus vaccination schedule: a 7-year follow up

The immune response to diphtheria and tetanus toxoid components of a combined diphtheria tetanus whole-cell pertussis/enhanced inactivated poliovirus (DTwP/eIPV) vaccine, administered in a three-dose schedule to infants at 2, 3 and 10 months of age and followed by a booster at the age of 8 years, was compared with the immune profile of a group of children at the same ages given the customary DTwP vaccine schedule at 2, 4, 6, and 12 months of age and a booster at the age of 8. Diphtheria- and tetanus-antitoxin titers were measured in parallel enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). After the reinforcing dose given at 10 months of age, diphtheria antitoxin concentrations of 0.01 IU/ml were found in 100% of infants in the study group, 91.7% of whom reached a titer of 0.1 IU/ml and a geometric mean titer (GMT) of 0.40 and 0.93 IU/ml in ELISA and RIA, respectively. At 3 and 6 years of age, diphtheria antitoxin values of 0.01 IU/ml were detected in 100 and 94% of children with GMT of 0.043 and 0.024 IU/ml, respectively. Seropositivity and GMT values indicative of protection were measured by both ELISA and RIA after the booster at the age of 8 years. Similar results were found in the control group, although the GMT tended to be higher. A good correlation between results obtained by ELISA vs. RIA was evident throughout. Priming at 2 and 3 months with diphtheria and tetanus antitoxin, as a component of a DTwP program, and reinforcing 6 months later induced an immune response indicative of protection against the diseases, which persisted up to the age of the booster recommended at school entry.     

Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib

This study investigated the immunogenicity and safety of including a Haemophilus influenzae type b vaccine (polyribosylribitol phosphate conjugated to tetanus toxoid, PRP-T) in three different vaccination schemes: (1) PRP-T reconstituted with a combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccine (DTP-IPV//PRP-T); (2) PRP-T reconstituted with DTP and administered concomitantly with an oral poliovirus vaccine (DTP//PRP-T+OPV); and (3) PRP-T administered concomitantly with DTP at a different injection site and OPV (DTP+PRP-T+OPV). Vaccines were given at 2, 4, and 6 months of age. A total of 252 infants were enrolled, and randomly assigned to one of the three vaccination groups (84 infants in each group); 241 infants were followed until the end of the study. Antibody production against PRP, diphtheria, tetanus and pertussis antigens was satisfactory for each vaccination scheme used. A good response to Hib vaccine was elicited in each group, and 3 months after the third vaccine dose, at least 97% of children in each group had levels of PRP antibody considered to be seroprotective (>0.15 microg/ml), and over 90% of children in each group had levels over 1. 0 microg/ml. The solicited local and systemic adverse events following vaccination were mild in all groups and resolved within 4 days without medical intervention. With the exception of fever, which was more common after the second dose in children who received DTP-IPV//PRP-T, local and systemic reactions did not differ between the vaccination groups. Due to the practical advantages of combined vaccines, their use in routine immunization programs in developing countries is highly desirable. Our results show that Hib conjugate vaccine can be included in routine immunization programs that include either OPV or IPV with satisfactory immunogenicity and safety profiles. This flexible approach should facilitate the inclusion of the Hib conjugate vaccine in routine immunization programs on a world-wide scale.     

Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.     

Antitoxins for diphtheria and tetanus decline more slowly after vaccination with DTwP than with DTaP: A study in a Chinese population

Objectives

DTP vaccines are used for the prevention of pertussis, diphtheria and tetanus. In 2007, in Gaobeidian city, China, the DTwP vaccine was replaced with DTaP. This study described the diphtheria and tetanus sero-epidemiology in subjects vaccinated solely with DTwP or DTaP.

Methods

Blood samples were obtained between October 2012 and June 2013 from 587 healthy subjects aged 2–17 years. Serum IgG antibodies against diphtheria and tetanus were determined using ELISA. Interrupted time series analyses examined the changes in antitoxin levels over time and analyzed the alterations in diphtheria and tetanus antitoxin levels after the vaccine switch.

Results

Mean concentrations of diphtheria antitoxin and tetanus antitoxin were 0.074 IU/ml (95% CI 0.065–0.084) and 0.063 IU/ml (95% CI 0.053–0.076). The protection rates (antitoxins >0.01 IU/ml) for diphtheria and tetanus were 88.25% and 82.11%. Mean antitoxin levels for both diphtheria and tetanus decreased with increasing age, but this decrease was much slower for DTwP than DTaP.

Conclusions

Although the observed protection rates for diphtheria and tetanus were sufficient to prevent an outbreak at present, the means levels of diphtheria and tetanus antitoxins decreased with increasing age; therefore, booster vaccinations at 7 and 12 years of age would be strengthened in Gaobeidian city, China.     

Response and persistence of antibodies to PRP-T and DTwP vaccines with concomitant administration of conjugate vaccines

We first studied the immunogenicity of PRP-T and DTwP vaccines in Filipino infants given at 6, 10 and 14 weeks concomitantly with either an aluminum adjuvanted eleven-valent pneumococcal conjugate vaccine (11PncTD) or a meningococcal diphtheria-conjugated vaccine as compared to a control group that received only DTwP/PRP-T. The GMCs and proportions of infants achieving protective antibody concentrations to DTwP and PRP-T vaccine antigens were similar among the groups. In the second phase, the control group received 11PncTD at 18 weeks and the antibody concentrations were measured at 9 months in all children; 11PncTD induced a booster response to diphtheria in the control group. There was no negative interference from concomitant administration of new conjugate vaccines. In contrast, 11PncTD can boost the antibody response to the carrier proteins.     

Immunogenicity of a low-dose diphtheria,tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria,tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap–IPV, Repevax^®; Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis^®; Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap–IPV, Tetravac^®; Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection.All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01 IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap–IPV, Tdap + OPV and DTap–IPV, respectively, had protective antitoxin levels greater than 0.1 IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV.Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.     

Immunogenicity study of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine used to reconstitute a freeze-dried Haemophilus influenzae type b vaccine (DTaP-IPV//PRP-T) administered simultaneously with a hepatitis B vaccine at two, three and four months of life

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (?trade mark omitted?) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.     

Antibody persistence, PRP-specific immune memory, and booster responses in infants immunised with a combination DTPa-HBV-IPV/Hib vaccine

A new single-injection combination vaccine against six diseases has been developed to accommodate the growing number of recommended paediatric vaccines. A pentavalent liquid diphtheria, tetanus, acellular pertussis (3-component), hepatitis B, and inactivated polio (types 1-3) combined vaccine (DTPa-HBV-IPV) is extemporaneously mixed with a lyophilized Haemophilus influenza type B (Hib) conjugate vaccine (polyribosyl-ribitol phosphate (PRP)-T) and given as a single-injection. A cohort of 368 healthy infants was initially studied to evaluate the immunogenicity and reactogenicity of this hexavalent combination given as a primary course at 2, 4, and 6 months of age. At 15 months of age, from this cohort, 219 children received a booster dose of a licensed DTPa/Hib (PRP-T) vaccine to assess the booster response, while 70 received a challenge dose of unconjugated PRP (PRP) vaccine (to evaluate Hib-specific memory) plus a separate DTPa vaccine. Seven to 10 days following plain PRP challenge, anti-PRP geometric mean antibody concentrations (GMCs) had increased 13-fold to 5.67 microg/ml, and thirty days after conjugated PRP booster vaccination, anti-PRP antibody GMCs increased 102-fold. Both responses are indicative of immune memory. Vaccination was well tolerated following all primary and booster doses, although 10.5% of booster recipients experienced >50-mm local swelling at the site of DTPa vaccination. We conclude that DTPa-HBV-IPV/Hib is safe and immunogenic for primary vaccination, and that Hib-specific memory is induced by primary vaccination.     

Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children

The effects of vitamin A and vitamin E supplementation on the IgG response to tetanus toxoid after primary immunization were evaluated in a prospective, randomized controlled clinical trial involving 89 healthy infants with normal serum vitamin A and E levels at 2 months of age. Before the first dose of DPT vaccine, the infants were randomly enrolled into four different study groups [Group I (n=24): 30,000 IU vitamin A for 3 days just after each three doses of primary vaccination, Group II (n=21): 150 mg oral vitamin E for only 1 day after the injections for primary immunization, Group III (n=21): vitamins A and E together in the same order, Group IV (n=23) no vitamin after DPT vaccines]. Serum tetanus antitoxin (IgG) titres were measured three times; initially at 2 months of age before the first dose of DPT, secondly at 5 months of age 1 month after primary immunization and thirdly at 16-18 months of age before the booster dose of DPT. Before the first dose of the DPT vaccine, 1 month after the third DPT injection and at 16-18 months before the booster dose of DPT, there was no significant difference in serum tetanus antitoxin levels between these four groups. A significant increase was observed in all the groups when serum tetanus antitoxin levels before (2 months) and after (5 months) primary immunization were compared. In addition, serum antibody levels against tetanus significantly decreased in the four groups before booster vaccination. Before the beginning of primary immunization, 15 infants (16.8%) had serum tetanus antitoxins (IgG) below protective level. After three doses of DPT, all the infants had protective antitoxin levels. At 16-18 months of age before booster dose, four infants (10%) also had serum tetanus antitoxins (IgG) below the protective level. No side-effects were observed except bulging fontanelle in two infants in Group I.     

Booster response to the tetanus and diphtheria toxoid carriers of 11-valent pneumococcal conjugate vaccine in adults and toddlers.

We measured the tetanus and diphtheria antitoxin responses after administration of one dose of a mixed carrier (tetanus and diphtheria toxoids) 11-valent pneumococcal conjugate vaccine (PncDT) in 20 Finnish adults (mean age 26.1 years) and 20 Finnish (mean age 23.2 months) and 23 Israeli (mean age 18.5 months) toddlers. The vaccinees had previously been immunised with multiple doses of vaccines containing diphtheria and tetanus toxoids. A double-antigen ELISA was used to measure the antitoxin concentrations. PncDT induced significant booster responses in both adults and toddlers to the tetanus and the diphtheria carrier proteins. Thus, the effect on the tetanus and diphtheria immunity of multivalent conjugate vaccines containing tetanus and diphtheria toxoids as carriers needs to be evaluated before such vaccines are routinely implemented.     

Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell and acellular)-Haemophilus influenzae-b conjugate vaccines administered to Indonesian children

A randomized double-blind trial was conducted to evaluate the safety and immunogenicity of vaccines comprised of diphtheria (D) and tetanus (T) toxoids combined with either a whole cell (P) or an acellular (aP) pertussis component and Haemophilus influenzae type b polyribosylphosphate (PRP) tetanus toxoid conjugate (PRP-T) in Indonesian infants. Three doses of either DTaP, DTaP-PRP-T, or DTP-PRP-T were administered to 930 infants approximately 2-3 months of age and at 2 month intervals thereafter. A booster dose of either DTP-PRP-T or DTaP-PRP-T was administered at 15-18 months of age. Both local and systemic reactions occurred at a significantly (p < 0.001-0.026) higher rate in the group that received whole cell pertussis vaccine versus groups which were immunized with aP containing vaccines. There was no significant difference (p > 0.05) in the rate of adverse events between groups immunized with DTaP or DTaP PRP T. One month after the third dose of vaccine, 99% of subjects had achieved > or =0.1 IU of anti-D and anti-T antibody per ml of serum. The geometric mean titer (GMT) to D was significantly (p < 0.001) higher in the group immunized with DTaP versus the other two groups whereas the anti-T GMT was significantly (p < 0.006) higher for the group immunized with DTP-PRP-T. Both the anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibody levels were significantly (p < 0.001) higher in recipients of acellular versus whole cell pertussis vaccine. In contrast, the anti-B. pertussis agglutinating antibody response was significantly (p < 0.0001) higher in the group immunized with whole cell pertussis vaccine. The anti-PRP GMTs (microg antibody/ml) at 7 months were 0.096, 3.35 and 6.11 for groups immunized with DTaP, DTaP-PRP-T and DTP-PRP-T, respectively. The GMT for those immunized with DTP-PRP-T was significantly (p < 0.001) higher compared to recipients of DTaP-PRP-T. The percent of children who attained > or =0.15 or > or =1 microg/ml after immunization was 18 and 2% for the DTaP group, 93 and 76% for the DTaP-PRP-T group and 97 and 88% for the DTP-PRP-T group. At the > or =1 microg/ml level the difference between the DTaP-PRP0-T and DTP-PRP-T groups was significant (p < 0.01). Children immunized with either DTaP, DTaP-PRP-T, or DTP-PRP-T were reimmunized with DTaP-PRP-T whereas a portion of children immunized with DTP PRP T where also boosted with this vaccine at 15-18 months of age. There was a vigorous anamnestic response to the D and T components with all children possessing > or =0.1 IU/ml. There was also a substantial increase in anti-PT, anti-FHA and B. pertussis agglutinating antibodies. The poorest anti-PT response was seen among children receiving DTP-PRP-T for both primary and reimmunization while the highest agglutinating antibody response followed receipt of 4 doses of DTP-PRP-T. Greater than 80% of children immunized with either DTP PRP T or DTaP-PRP-T possessed > or =0.15 microg/ml before boosting versus 38% for those vaccinated with DTaP (p < 0.001). Primary immunization with DTP-PRP-T resulted in a significantly (p < 0.05) higher percentage (72%) maintaining > or =1 microg/ml compared to those immunized with DTaP-PRP-T (46%). Prior to reimmunization, the anti-PRP GMT was significantly (p < 0.005) higher for children immunized with 3 doses of DTP-PRP-T versus DTaP-PRP-T. Subsequent to reimmunization, > or =95% of subjects attained > or =1 microg/ml.     

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III,randomized, observer-blind,multicenter, parallel-group study

BackgroundBroad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1 year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013.MethodsWe compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM₁₉₇) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria–tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM₁₉₇ or PRP-T vaccines. The primary endpoint was the “long-term seroprotection rate”, defined as the group proportion with anti-PRP antibody titers ⩾1.0 μg/mL, after the primary series.ResultsLong-term seroprotection rates were 99.3% in the PRP-CRM₁₉₇ group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM₁₉₇ group – PRP-T group) was 3.7% (95% confidence interval: 0.099–7.336), demonstrating that PRP-CRM₁₉₇ vaccine was non-inferior to PRP-T vaccine (p < 0.0001). Furthermore, the “short-term seroprotection rate” (anti-PRP antibody titer ⩾0.15 μg/mL) before booster vaccination was higher in the PRP-CRM₁₉₇ group than in PRP-T. Concomitant administration of PRP-CRM₁₉₇ vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM₁₉₇ vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles.ConclusionThe immunogenicity of PRP-CRM₁₉₇ vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1 year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846     

Clinical trial of hepatitis B vaccine in a simplified immunization programme

A study was conducted in the rural areas of Senegal to assess the immunogenic effect of 2 doses of hepatitis B vaccine with a 6-month interval followed by a booster dose after another month and to compare them with those obtained using 2 doses of a vaccine with a 2-month interval or 3 doses at 1-month intervals. The study population of infants received 3 injections of hepatitis B vaccine at 6-month intervals (T0, T6, and T12, respectively), with the 3rd dose as a booster. Other vaccines also were administered to subsets of children: BCG and diphtheria/tetanus/pertussis-polio (DTP-polio) at T0 and DTP-polio at T6 and T12. 664 infants received the 1st dose of hepatitis B vaccine, 409 the 2nd dose, and 177 the 3rd dose. Blood samples were taken at the time of each injection and in the case of 89 infants also 2 months after the last (booster) dose. Only 26.7% of the infants completed the entire series of injections. Only results from infants who were seronegative at T0 are presented, i.e., 281 infants at T6, 116 at T12, and 65 at T14. At T0 the mean age of the seronegative infants was 10.2 months and that of the seropositive infants with anti-HB antibodies was 7.4 months. The mean age of infants who were only anti-HBc-positive was 4.8 months and that of infants who were already HBsAg-positive at T0 was 14.3 months. The results were compared with those reported for 2 other groups of Senegalese infants: 72 seronegative infants who were immunized using a protocol of 2 doses of hepatitis B vaccine with a 2-month interval; and 111 seronegative infants immunized using 3 doses at 1-month intervals. Both groups also received a booster 12 months after the 1st dose. The anti-HBs response was determined 6 months after the T0 dose of hepatitis B vaccine for the 281 infants who were seronegative. 185 of these children (65.8%) exhibited anti-HB antibodies, but the geometric mean titre (GMT) was only 6.1 mlU/ml. The anti-HBs response of the 116 infants who received the 2nd dose of vaccine was determined when the 3rd (booster) injection was given (T12): 104 were positive for anti-HBs (89.7%), and the anti-HBs GMT was 83.7 mlU/ml. Assay of blood samples from 65 infants 2 months after the booster dose indicated that 62 (95.4%) had anti-HBs antibodies, the anti-HBs GMT reaching 348 mlU/ml. The study results establish that infants administered two 5-mcg doses of hepatitis B vaccine with a 6-month interval exhibit a seroconversion rate and antibody levels comparable to those produced using a protocol comprising 2 doses with a 2-month interval or 3 doses at 1-month intervals.     

Tetanus immunity in individuals aged 50 years or older in Kashan, Iran

Tetanus can be only prevented by vaccination because immunity against this disease is rarely acquired, even by natural infections. To maintain long-term protective immunity against tetanus, booster immunization is essential for adolescents and adults. Most hospitalized cases and virtually all deaths occur in people over 60 years of age. The purpose of this study was to investigate the degree of protective tetanus immunity among 50 years of age and older people in Kashan city, Iran. This cross-sectional study carried out on 180 randomly individuals aged 50 years or older who were visiting a central laboratory for health examinations in 2008. Participants' serum levels of tetanus antitoxin were measured by enzyme linked immunosorbent assay. A standard questionnaire was used to collect demographic data and information about risk factors. The prevalence of protective tetanus immunity in various age groups was described and sociodemographic factors that potentially influenced the degree of tetanus immunity were analyzed. Overall, 180 persons were included. Of these, 72 (40%) had never received a toxoid booster, while 47 (26.1%) had received a booster at least once. Among all participants, 30 (16.7%) had protective tetanus antitoxin levels (≥ 0.11 IU/mL), and 34 (18.9%) had protective antitoxin levels without the need of an immediate booster ≥0.51 IU/mL. Among 86 participants aged >60 years, 6 (7%) had protective antitoxin levels ≥0.1-1 IU/mL, and 5(5.8%) had protective antitoxin levels ≥1 IU/mL. Male gender and prior receipt of toxoid booster(s) were associated with protective tetanus immunity. Tetanus antitoxin levels declined with age. It appears that most 50 years of age and older adults do not have protective levels of tetanus antitoxin because of inadequate vaccination coverage. There is a need to improve the immunity levels of this age group. It is recommended to vaccinate elderly people against tetanus.     

我国白喉流行病学特点分析

目的对上海市嘉定区健康人群白喉抗体水平监测分析, 评价白喉类毒素接种策略效果。方法2010-2013年在该区采集健康人群血清标本, 利用酶联免疫吸附试验(ELISA)检测白喉抗体, 比较不同人群白喉抗体几何平均滴度(GMT)。结果共调查1 029人, 白喉IgG抗体GMT为0.325 IU/mL。白喉IgG抗体滴度达到部分保护水平(≥0.01 IU/mL)者1 003人, 阳性率为97.47%;达到安全保护水平(≥0.1 IU/mL)占70.36%;达到长期保护水平(≥1.0 IU/mL)占35.57%。上海市户籍和外地户籍之间白喉抗体的阳性率和抗体水平差异有统计学意义(χ²=4.708, P < 0.05;t=2.787, P < 0.05)。不同年龄组之间白喉抗体阳性率的差异有统计学意义(χ²=30.262, P < 0.001)。各年龄组GMT在0.029 IU/mL (30~岁)~1.526 IU/mL (5~岁)之间, 不同年龄组之间的白喉抗体GMT差异有统计学意义(F=99.500, P < 0.001)。结论上海市嘉定区白喉抗体水平调查结果可真实反映该区白喉常规免疫的接种效果, 初中三年级白破(DT)疫苗接种效果显著, 可考虑青少年或成人适时接种1剂次含白喉类毒素成分的疫苗以维持免疫水平。     

Use of tetanus-diphtheria (Td) vaccine in children 4–7 years of age: World Health Organization consultation of experts

For lifetime protection against diphtheria and tetanus, the World Health Organization (WHO) recommends six doses of diphtheria and tetanus containing vaccines. Td (reduced diphtheria toxoid, ≥2–5 IU) vaccines are currently licensed for ages 7 years and older, but use of Td vaccine for ages 4 years and older would have advantages for immunization programs in many low- and middle-income countries. For this reason, WHO convened an expert consultation to review the currently available evidence for the use of Td vaccine from 4 to 7 years of age which concluded: (1) no relevant biological difference in immune response in the relevant age group compared with children over 7 years of age; (2) adequate seroprotection in several studies with Td vaccine in the 4–7 age group and many studies using combination vaccines; (3) durable and protective response of at least 9–11 years duration in several longitudinal and modelling studies, (4) less reactogenicity compared with use of full-dose diphtheria vaccine, potentially improving the vaccination experience; and (5) adequate control of diphtheria in several countries using Td-containing combination vaccines in 4–7 year old children. On this basis, the experts concluded that from a programmatic perspective, Td vaccine given in ages 4–7 years, as a second booster dose in a six-dose series, would provide adequate protection against diphtheria and tetanus and recommended steps to include this change in age extension listed in the package insert.     

Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine

Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml. The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005). Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline. These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T antibody levels after immunization.     

Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.     

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.