Safety and immunogenicity of a new formulation of a pentavalent DTwP-HepB-Hib vaccine in healthy Indian infants-A randomized study.

BACKGROUND: Pentavalent vaccines (DTP-HepB-Hib) have been introduced in many countries in their routine public immunization programmes to protect against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (Hep B) and Hemophilus influenzae type b (Hib) diseases. This study compared the safety and immunogenicity of a new formulation of a whole-cell Bordetella pertussis (wP) based pentavalent vaccine (DTwP-HepB-Hib). The new formulation was developed using well-characterized hepatitis B and pertussis whole cell vaccine components. METHODS: This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6-8, 10-12 and 14-16 weeks of age. RESULTS: The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89-1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73-1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. CONCLUSIONS: The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry India number: CTRI/2018/12/016692.

Hepatitis B surface antigen prevalence and the rates of mother-to-child transmission of hepatitis B virus after the introduction of infant vaccination programs in South East Asia and Western Pacific regions: a systematic review.

OBJECTIVES: Infant vaccination against the hepatitis B virus began in the World Health Organization South East Asia Region and the Western Pacific Region between 1983 and 2016. This systematic review examined the seroprevalence of hepatitis B surface antigen (HBsAg) in children and the rate of mother-to-child transmission (MTCT) in these regions between 1990 and 2020. METHODS: MEDLINE and EMBASE were searched for articles published between January 1990 and September 2020, which reported seroprevalence of HBsAg in children aged 0-15 years and/or the rate of MTCT in the South East Asia Region and Western Pacific Region. A pragmatic review identified supporting information. This review was registered in the International Prospective Register of Systematic Reviews (#CRD42020211707). RESULTS: Of 115 included studies, 77 (24 countries) reported HBsAg prevalence, and 38 (nine countries) reported MTCT. The seroprevalence of HBsAg ranged between 0.0% and 27.4%, with a decreasing trend over time in each country. MTCT rates were 0.0-5.2% in infants of mothers who are hepatitis B e antigen-negative and 2.7-53.0% in infants of mothers who are hepatitis B e antigen-positive. CONCLUSION: After the introduction of infant hepatitis B virus vaccination programs, the countries in South East Asia Region and Western Pacific Region observed a reduction in HBsAg seroprevalence in children. Nevertheless, the risk of MTCT persists, emphasizing the importance of antenatal screening to identify high-risk pregnancies.

A combined DTaP-IPV vaccine (Tetraxim®/Tetravac®) used as school-entry booster: a review of more than 20 years of clinical and post-marketing experience.

INTRODUCTION: Routine infant primary series and toddler booster vaccination are associated with waning of antibody levels over time, which can lead to an increased incidence of vaccine-preventable diseases. A diphtheria-tetanus-pertussis (DTP) booster vaccination at school-entry (aged 4-7 years) allows continued protection against these diseases and is included in many national immunization programs. AREAS COVERED: The available immunogenicity and safety data from 6 clinical studies of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTaP-IPV [Tetraxim®]) used as a school-entry booster vaccination were identified using a PubMed search or on file at Sanofi. The studies spanned a 15-year period (1995-2010) and were performed in different populations using different study designs, so all data were reviewed descriptively (no meta-analyses were conducted). Additionally, post-marketing experience was reviewed. EXPERT OPINION: Each vaccine antigen is highly immunogenic, and the safety profile of the vaccine is satisfactory. Post-marketing evaluations have shown the effectiveness of a school-age booster, particularly against increased pertussis disease incidence around the time of school entry and the associated risk of spreading the disease through contact with younger vulnerable infants. School-entry provides an ideal opportunity to implement DTaP-IPV vaccination to close the gap between waning immunity from the previous infant/toddler vaccination and future adolescent vaccination.

Post-Marketing Surveillance of Tetravalent Diphtheria-Tetanus-Acellular Pertussis and Inactivated Poliovirus (DTaP-IPV) Vaccine in South Korea, 2009 to 2015.

INTRODUCTION: TETRAXIM™ (Sanofi), a combined diphtheria, tetanus, acellular pertussis, and inactivated poliovirus (DTaP-IPV) vaccine, has been licensed in South Korea since 2009. In accordance with the Ministry of Food and Drug Safety regulations, this post-marketing surveillance (PMS) study evaluated the safety of the DTaP-IPV vaccine in real-world clinical practice in infants and children who received it as either a part of the three-dose primary series dose at 2, 4, and 6 months or school entry booster between 4 and 6 years of age. METHODS: This multicenter, observational, PMS study was conducted in real-world practice in South Korea for 6 years (2009-2015) in participants aged between 2 months and 6 years. The study outcomes included solicited reactions, unsolicited adverse events (AEs)/adverse drug reactions (ADRs), unexpected AEs/ADRs, and serious AEs (SAEs)/ADRs. RESULTS: Data from 647 participants was included in the safety analysis. Overall, 268 AEs were reported by 181 (28%) participants: 47 (17.5%) solicited reactions, 220 (82.1%) unsolicited AEs, and 1 (0.4%) unsolicited ADR. A total of 48 AEs (including 47 solicited reactions) were reported to have a causal relationship with the DTaP-IPV vaccine and were reported by 36 (5.6%) participants. A total of 212 unexpected AEs were reported by 152 (23.5%) participants, none of which had a causal relationship with the DTaP-IPV vaccine. Neither immediate AEs nor SAEs were reported during the study. Among the participants who reported AEs, 220 (34%) were on concomitant medications. Most AEs were of mild intensity, and all participants recovered. CONCLUSION: No safety concerns related to the DTaP-IPV vaccine in a real-world setting were raised in participants aged 2-6 months for the primary series and 4-6 years for the school-entry booster dose in the Korean population. The DTaP-IPV vaccine was well tolerated and can be continued as part of routine immunization programs in infants and children. TRIAL REGISTRATION: NCT01437423.

Immunogenicity and safety of a hexavalent pediatric vaccine in HIV-exposed infected and uninfected infants in Republic of South Africa.

Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15-18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan.

BACKGROUND: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants. METHODS: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10). All subjects received a 3-dose primary vaccination series and a booster. Non-inferiority (Group A versus Group B) was tested post-primary series and subsequent post hoc analyses were performed for anti-Hib. Safety was assessed by parental reports. RESULTS: Non-inferiority for SC administration of Group A versus Group B for the primary series was demonstrated for antibody responses to all antigens except Hib using the threshold of 1.0 µg/mL. Post hoc analyses for anti-Hib demonstrated non-inferiority for the primary series response using 0.15 µg/mL, and for pre-booster antibody persistence and the booster response using 0.15 µg/mL and 1.0 µg/mL. The immune response was similar for each antigen following SC or IM administration. There were no safety concerns in any group, and a lower incidence of injection sites for the IM route was observed as expected. CONCLUSIONS: These data show the good immunogenicity and safety profile of the DTaP-IPV/Hib vaccine as a 3-dose infant primary series followed by a booster in the second year of life in Japan.

Persistence of hepatitis B immune memory until 9-10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP∼T vaccination at 2, 4 and 6 months.

OBJECTIVE: To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™). METHODS: Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12-18 months of age and 9-10 years of age. A monovalent HB challenge re-vaccination was administered at 9-10 years of age and the anamnestic response was evaluated. RESULTS: Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12-18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9-10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively). CONCLUSION: The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.

Immunogenicity and Safety of a Liquid Hexavalent Vaccine in Indian Infants.

OBJECTIVE: To evaluate the immunogenicity and safety of a fully liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV- HB-PRP~T) vaccine in Indian infants. DESIGN: Phase III, single-arm study. SETTING: Two tertiary care hospitals. PARTICIPANTS: 177 healthy, 6-week-old infants. INTERVENTION: All participants received hepatitis B vaccine and Oral polio vaccine (OPV) at birth and DTaP-IPV-HB-PRP~T at 6, 10, 14 weeks of age. MAIN OUTCOME MEASURES: Serum was analyzed for immune responses to all antigens 1 month post- 3rd dose; safety was assessed for 30 minutes post-vaccination, and for 7 days (solicited reactions) and 30 days (unsolicited events). RESULTS: Seroprotection rates were 100% for anti-HB (>10 mIU/mL), anti-PRP (>0.15 ug/mL), anti-T (>0.01 IU/mL), anti-polio 1, 2, and 3 (>8 [1/dil]), and 99.3% for diphtheria (>0.01 IU/mL). For the pertussis antigens, vaccine response rate was 93.8% for anti-PT and 99.3% for anti-FHA. 37.9% and 54.6% of participants experienced at least one solicited injection site and systemic reaction, respectively, and 20.3% of participants experienced at least one unsolicited event (none of which was related to the vaccination). Four serious adverse events (including one death) were reported, but none was related to the vaccination. CONCLUSION: The fully liquid DTaP-IPV-HB-PRP~T vaccine is highly immunogenic in infants in India when administered in a 6, 10, 14 week schedule along with HB and OPV administered at birth, and was well tolerated.

Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools.

INTRODUCTION: The manufacture of DTP-backboned combination vaccines is complex, and vaccine quality is evaluated by both batch composition and conformance of manufacturing history. Since their first availability, both the manufacturing regulations for DTP combination vaccines and their demand have evolved significantly. This has resulted in a constant need to modify manufacturing and quality control processes. Areas covered: Regulations that govern the manufacture of complex vaccines can be inconsistent between countries and need to be aligned with the regulatory requirements that apply in all countries of distribution. Changes in product mix and quantities can lead to uncertainty in vaccine supply maintenance. These problems are discussed in the context of the importance of these products as essential public health tools. Expert commentary: Increasing demand for complex vaccines globally has led to problems in supply due to intrinsically complex manufacturing and regulatory procedures. Vaccine manufacturers are fully engaged in the resolution of these challenges, but currently changes in demand need ideally to be anticipated approximately 3 years in advance due to long production cycle times.

Immunogenicity of Two Different Sequential Schedules of Inactivated Polio Vaccine Followed by Oral Polio Vaccine Versus Oral Polio Vaccine Alone in Healthy Infants in China.

BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule. METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored. RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar. CONCLUSIONS: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

Diphtheria, tetanus and poliovirus antibody persistence 5 years after vaccination of pre-schoolers with two different diphtheria, tetanus and inactivated poliomyelitis vaccines (Td-IPV or DT-IPV) and immune responses to a booster dose of DTaP-IPV.

INTRODUCTION: This follow-up study assessed the 5-year persistence of vaccine-induced antibodies (Td-IPV or DT-IPV) and the immune response to a booster dose of DTaP-IPV. METHODS: This was an open-label, parallel-group (two arms), multicentre trial performed at 44 study sites in France. Children aged 11-13 years, of either sex, who received Td-IPV (Revaxis(®)) and DT-IPV (DT Polio(®)) vaccines at 6 years of age in one previous open-label trial with no further vaccination against diphtheria, tetanus, pertussis or poliomyelitis, were enrolled. All participants received a single intramuscular booster dose (0.5mL) of DTaP-IPV vaccine (Tetravac-Acellulaire(®)). Study endpoints were based on antibody persistence and post-booster immune responses. Safety was monitored throughout the study. Descriptive statistics were used for all analyses. RESULTS: Of the 758 children included in the previous study, 274 were included in this follow-up study; 129 had previously been vaccinated with Td-IPV, and 145 had previously received DT-IPV. At least 96.5% of participants in both groups presented an anti-diphtheria and anti-tetanus concentration ≥0.01IU/mL, and anti-poliovirus types 1-3 titres≥8 (1/dilution). Following vaccination with DTaP-IPV, anti-diphtheria and anti-tetanus antibody concentrations ≥0.1IU/mL and anti-poliovirus types 1-3 antibody titres ≥8 (1/dilution) were achieved in all participants. DTaP-IPV was well tolerated in this study. There were no serious adverse events during the study, and no participant withdrew because of adverse events. DISCUSSION: The present study confirmed the long-term immunity conferred by Td-IPV when given as a booster dose, and supports the use of Td-IPV as a second booster at 6 years of age in children previously vaccinated against diphtheria, tetanus and poliomyelitis types 1-3.

Fully liquid DTaP-IPV-Hib pediatric combination vaccine (Pediacel): a review of 18 years of clinical experience.

Safe and effective combination pediatric vaccines are necessary to simplify complex immunization schedules and to improve coverage and protection for children worldwide. We provide an overview of the 18 years of clinical and worldwide experience with DTaP-IPV-Hib (Pediacel(®)), a unique fully liquid pentavalent vaccine (diphtheria [D], tetanus [T], acellular pertussis, inactivated poliovirus [IPV], Haemophilus influenzae type b [Hib]). Pediacel has demonstrated good and lasting immunogenicity in many populations, with differing primary series and booster schedules, and with a variety of coadministered vaccines. The acellular pertussis antigens have proven efficacy and real-world effectiveness. Clinical and post-marketing studies confirm the safety of Pediacel. Pediacel can be used for primary series and toddler booster doses, as well as in mixed pediatric vaccine schedules.

Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines.

OBJECTIVE: Comparison of a fractional inactivated poliovirus vaccine (IPV) dose administered intradermally (ID) to a full dose administered intramuscularly (IM). METHODS: Healthy Filipino infants were randomized to receive IPV as either a fractional (1/5(th)) dose ID by needle injection or a full dose IM at 6, 10, and 14 weeks and a booster at 15-18 months of age. Pre- and post-vaccination anti-polio 1, 2, and 3 titers were estimated. Adverse events were monitored throughout the study. RESULTS: Following primary series vaccination, anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in 99-100% of participants, and the ID route was non-inferior to the IM route. Depending on the study group, antibody persistence was detected in 83-100% of participants, and the booster dose resulted in a strong anamnestic response in all groups. The incidence of adverse events in each group was similar, except for injection-site erythema (higher in the ID group). CONCLUSIONS: Primary series and booster vaccination of a fractional IPV dose administered by the ID route was highly immunogenic and well tolerated. These data confirm the medical validity of using fractional ID doses of IPV. The programmatic feasibility of implementing affordable mass vaccination programs based on this delivery mode has yet to be established.

Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS (®)) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio (®)) given as a booster dose at 6 years of age.

This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Non-inferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%), and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age.

Repertoire of antibodies against type 1 poliovirus in human sera.

A blocking-ELISA procedure was used to quantify antibodies in sera of humans immunized with poliovirus vaccines. Titers determined by this method demonstrated an excellent correlation with the results of neutralization test. Testing of serum potency with a panel of type 1 poliovirus strains altered antigenically was used to evaluate the composition of polyclonal sera with respect to the epitope specificity of constituent antibodies. Paratope profiles of various polyclonal sera determined by this new method differed, depending on the type of vaccine used for immunization. Antibodies induced in response to inactivated poliovirus vaccine (IPV) contained antibodies directed primarily against antigenic site 1, while sera from recipients of the oral poliovirus vaccine (OPV) contained antibodies to site 3. Antibodies to antigenic sites 2 and 4 were minor constituents in both types of sera. Pre-immunization sera had paratope profiles similar to OPV-induced antisera, allowing the discrimination between antibodies induced by IPV and maternal antibodies. The new method may be useful for analyzing results of clinical trials and to compare immunity induced by different poliovirus vaccines.

Immunogenicity of a two-component (PT & FHA) acellular pertussis vaccine in various combinations.

Immunogenicity data for the pertussis components of the French diphtheria-tetanus-two component acellular pertussis vaccine (DTaP(2Fr)) obtained after primary series of immunizations were compiled from 75 study groups comprising 36 clinical trials or vaccination programs conducted between 1987 and 2006. DTaP(2Fr) vaccine was administered either as a standalone vaccine or as the backbone of several combination vaccines that included IPV, HepB and/or PRP-T antigens. Most of the variability in responses was associated with differences in the schedules, and to a lesser extent the geographical region where the study was performed, suggesting the importance of ethno-ecological factors. However the addition of other vaccine antigens did not affect the immunogenicity of the aP(2Fr) antigens. The immune responses to the PT and FHA antigens of the DTaP(2Fr) vaccine used in the Sénégal efficacy trial, which established its good efficacy relative to a highly effective DTwP vaccine, was in the middle of the range of titers observed during other studies using the 2-4-6 months schedule conducted with the same vaccine. The consistent immunogenicity of the DTaP(2Fr) vaccine is accompanied by effectiveness in controlling pertussis disease in the areas where it is used on a large scale with good vaccination coverage.

Immunological priming of one dose of inactivated hepatitis A vaccine given during the first year of life in presence of maternal antibodies.

BACKGROUND: In hepatitis A virus (HAV)-seronegative infants, inactivated hepatitis A vaccines are highly immunogenic. On the contrary, in infants who are HAV-seropositive before vaccination, the interfering effect of passively-transferred maternal anti-HAV antibodies leads to lower post-primary immunization anti-HAV levels, as compared to those achieved by seronegative infants. One possible way to overcome this drawback is to delay hepatitis A vaccination later during the first year of life. The objective of the study was to document the immunogenicity of an inactivated hepatitis A vaccine in 6 months old HAV-seropositive infants, given as two dose regimen consisting of a single primary immunization at 6 months of age, followed by a booster dose 6 months later. METHODS: The immunogenicity of one hepatitis A vaccine (Avaxim pediatric, Aventis Pasteur) was documented in 108 6 months old, HAV-seropositive infants randomly assigned to receive one priming dose of hepatitis A vaccine either concomitantly with (Group 2) or 2 weeks after the third dose of routine diphteria-tetanus-whole cell pertussis reconstituting lyophilized tetanus conjugated Haemophilus influenzae type b (DTwcP//PRP approximately T) vaccine and oral poliomyelitis vaccine (OPV) (Group 1). A booster dose was given 6 months later, concomitantly with MMR vaccine. RESULTS: The 91 infants who were HAV-seropositive (ELISA titer >20 mIU/ml) at the moment of primo vaccination remained seropositive 1 month later. Geometric mean titers (GMT) decreased from 292 and 278 mIU/ml 1 month after the first dose, to 77.6 and 76.0 mIU/ml 6 months after, in Groups 1 and 2, respectively. Post-booster titers increased markedly in both groups, with GMTs of 1731 and 1866 mIU/ml and geometric mean post/pre-immunization titer ratios of 22.3 and 24.6, respectively. CONCLUSIONS: These results suggest that immunological priming induced by a single dose of Avaxim pediatric administered to 6 or 6.5 months old, HAV-seropositive infants is present and should not preclude the use of this vaccine in such populations.