search
Back to results

The Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Health Neonates

Primary Purpose

Virus Disease, DNA Virus Infections, Hepadnaviridae Infections

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Experimental recombinant hepatitis B vaccine, HBIG
Active Comparator hepatitis B vaccine
Experimental recombinant hepatitis B vaccine
Active Comparator recombinant hepatitis B vaccine.
Placebo Comparator recombinant hepatitis B vaccine
Sponsored by
Jiangsu Province Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Virus Disease focused on measuring safety, immunogenicity, HBV vaccine, perinatal transmission

Eligibility Criteria

undefined - 24 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. A group (A1-A2)Subjects born to a mother positive for both HBsAg and hepatitis B e antigen.

    • Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age)

    • Subjects with a 5-minute Apgar score ≥ 7.

    • Subjects with temperature <37.1°C on axillary setting

    • Subjects with a birth weight ≥ 2.5 kg.

    • Normal neonatal jaundice.

    • Written informed consent obtained from the parent(s) of the subject.
    • Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol.

  2. B group(B1-B2) Subjects born to a mother positive for HBsAg, but negative for the hepatitis B e antigen.

    • Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age)

    • Subjects with a 5-minute Apgar score ≥ 7.

    • Subjects with temperature <37.1°C on axillary setting

    • Subjects with a birth weight ≥2.5 kg.

    • Normal neonatal jaundice.

    • Written informed consent obtained from the parent(s) of the subject.

    • Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol

  3. C group（C1-C3）Subjects born to a mother negative for HBsAg, hepatitis Be Antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e-antigen.

    • Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age)
    • Subjects with a 5-minute Apgar score ≥ 7.
    • Subjects with temperature <37.1°C on axillary setting
    • Subjects with a birth weight ≥ 2.5 kg.
    • Normal neonatal jaundice.
    • Written informed consent obtained from the parent(s) of the subject.
    • Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol.

Exclusion Criteria:

  1. A group (A1-A2) Subjects born to a mother positive for both HBsAg and e Antigen.

    Exclusion criteria for the first shot • Subjects born to a mother positive for antibody to HBsAg. • Family history of seizures or progressive neurological disease. • Family history of congenital or hereditary immunodeficiency. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.

    • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

    • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy.

    • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period.

    • Born to a mother known or suspected to be positive for HIV.

    • Family history of congenital or hereditary immunodeficiency.
    • Children in care.
    • Neonatal jaundice requiring systemic treatment.
    • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
    • Major congenital defects or serious chronic illness, including perinatal brain damage.
    • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots
    • Dysgenopathy
    • Any reaction or hypersensitivity to the hepatitis B vaccines.
    • Acute infections
    • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
    • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

  1. B group (B1-B2) Subjects born to a mother positive for HBsAg, but negative for the hepatitis B e antigen.

    Exclusion criteria for the first shot • Subjects born to a mother positive for antibody to HBsAg or e antigen. • Family history of seizures or progressive neurological disease. • Family history of congenital or hereditary immunodeficiency.

    • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.

    • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

    • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy.

    • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period.

    • Born to a mother known or suspected to be positive for HIV.

    • Family history of congenital or hereditary immunodeficiency.

    • Children in care.

    • Neonatal jaundice requiring systemic treatment.

    • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

    • Major congenital defects or serious chronic illness, including perinatal brain damage.

    • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots

    • Dysgenopathy

    • Any reaction or hypersensitivity to the hepatitis B vaccines.

    • Acute infections

    • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.

      3 C group (C1-C3) Subjects born to a mother negative for HBsAg, hepatitis Be Antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e-antigen.

    Exclusion criteria for the first shot

    • Subjects born to a mother positive for antibody to HBsAg, or e antigen, or antibody to B core antigen or antibody to hepatitis B e-antigen.

    • Family history of seizures or progressive neurological disease.

    • Family history of congenital or hereditary immunodeficiency.

    • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.

    • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

    • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy.

    • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period.

    • Born to a mother known or suspected to be positive for HIV.

    • Family history of congenital or hereditary immunodeficiency.

    • Children in care.

    • Neonatal jaundice requiring systemic treatment.
    • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
    • Major congenital defects or serious chronic illness, including perinatal brain damage.
    • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots
    • Dysgenopathy
    • Any reaction or hypersensitivity to the hepatitis B vaccines.
    • Acute infections
    • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
    • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Sites / Locations

  • Jiangsu Provincial Center for Diseases Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Placebo Comparator

Arm Label

A1

A2

B1

B2

C1

C2

C3

Arm Description

health neonates born to mother with positive for both HBsAg and e antigen

health neonates born to mother with positive for both HBsAg and e antigen

health neonates born to a mother positive for HBsAg, negative for the hepatitis B e antigen

health neonates born to a mother positive for HBsAg, negative for the hepatitis B e antigen

health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb

health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb

health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb

Outcomes

Primary Outcome Measures

The immunogenicity of experimental recombinant HBV vaccines in healthy neonates on day 210
Immunogenicity testing will be chemiluminescence immunoassay on serum obtained on day 210 after first dose
The immunogenicity of experimental recombinant HBV vaccines in healthy neonates on day 360
Immunogenicity testing will be chemiluminescence immunoassay on serum obtained on day 360 after first dose

Secondary Outcome Measures

To evaluate the safety of recombinant HBV vaccines in the health neonates after first dose
assessment of adverse events through 30 days following first dose
To evaluate the safety of recombinant HBV vaccines in the health neonates after second dose
assessment of adverse events through 30 days following second dose
To evaluate the safety of recombinant HBV vaccines in the health neonates after third dose
assessment of adverse events through 30 days following third dose

Full Information

First Posted
May 10, 2010
Last Updated
September 16, 2010
Sponsor
Jiangsu Province Centers for Disease Control and Prevention
search

1. Study Identification

Unique Protocol Identification Number
NCT01183611
Brief Title
The Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Health Neonates
Official Title
The Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Health Neonates Born to Mother With Positive for Both HBsAg and HBeAg, Positive for HBsAg But Negative for HBeAg, Negative for HBsAg, HBeAg, HBeAb and HBcAb
Study Type
Interventional

2. Study Status

Record Verification Date
September 2010
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Jiangsu Province Centers for Disease Control and Prevention

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary safety objective of this study is to assess the safety of 10 mcg recombinant hepatitis B vaccine in the Chinese health neonates. The primary immunogenicity objective is to assess the antibody response following 3 doses immunization of the 10 mcg experimental dose and 10 or 5 mcg control dose, Participants will include up to 1740 healthy neonates. This is a randomized, double-blinded, Phase III study. This study is designed to investigate the safety, reactogenicity, and immunogenicity of 10ug recombinant hepatitis B vaccine (yeast). Subjects will be stratified by the mother with positive for both HBsAg and HBeAg, positive for the surface antigen but negative for HBeAg, negative for the HBsAg and HBeAg and HBeAb and HBcAb. Stratified 1: There are 180 neonates born to the mother with positive for both HBsAg and HBeAg will be randomized into two groups according to the ratio of 2:1. 120 subjects will receive the 10 mcg experimental vaccine and 60 subjects will receive 10 mcg control vaccine respectively. Stratified 2: There are 360 neonates born to the mother with positive for HBsAg but negative for HBeAg will be randomized into two groups according to the ratio of 2:1. 240 subjects will receive the 10 mcg experimental vaccine and 120 subjects will receive 10 mcg control vaccine respectively. Stratified 3: There are 1200 neonates born to the mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb will be randomized into 3 groups. 600 of them will receive the 10mcg experimental vaccine. 300 subjects will receive 10mcg control vaccine. And the other 300 subjects will receive 5mcg control vaccine. The recombinant hepatitis B vaccine will be administered at m0, 1 and 6. Following each immunization, safety will be measured by assessment of adverse events through 30 days following each vaccination, serious adverse events and new-onset chronic medical conditions through 6 months post the final vaccination (Day 180 after last vaccination). For the immunogenicity testing will apply the chemiluminescence immunoassay on serum obtained on the day 0, 210 and 360 after born.
Detailed Description
During the early 1980s, human plasma-derived hepatitis B vaccines were developed in China. The production of these vaccines has not been adequate to meet China's need. Since the introduction of recombinant vaccines which can be produced in large quantity, at low cost, the emphasis has been placed on a search for a recombinant hepatitis B vaccine. This vaccine is thought to be safe, immunogenic, particularly in infants born to carrier mothers. Since 1992, the 5mcg recombinant hepatitis B vaccine has been used as one of the vaccines in the expanded immunization programs (People's Republic of China). The 5ug recombinant hepatitis B vaccine (yeast) is efficacious in short time but not to persistent in neonates. The primary safety objective of this study is to assess the safety of 10 mcg recombinant hepatitis B vaccine in the chinese health neonates. The primary immunogenicity objective is to assess the antibody response following 3 doses immunization of the 10 mcg experimental dose and 10, 5 mcg control dose, Participants will include up to 1740 healthy neonates. The primary safety objective of this study is to assess the safety of 10 mcg recombinant hepatitis B vaccine in the Chinese health neonates. The primary immunogenicity objective is to assess the antibody response following 3 doses immunization of the 10 mcg experimental dose and 10 or 5 mcg control dose, Participants will include up to 1740 healthy neonates. This is a randomized, double-blinded, Phase III study. This study is designed to investigate the safety, reactogenicity, and immunogenicity of 10ug recombinant hepatitis B vaccine (yeast). Subjects will be stratified by the mother with positive for both HBsAg and HBeAg, positive for the surface antigen but negative for HBeAg, negative for the HBsAg and HBeAg and HBeAb and HBcAb. Stratified 1: There are 180 neonates born to the mother with positive for both HBsAg and HBeAg will be randomized into two groups according to the ratio of 2:1. 120 subjects will receive the 10 mcg experimental vaccine and 60 subjects will receive 10 mcg control vaccine respectively. Stratified 2: There are 360 neonates born to the mother with positive for HBsAg but negative for HBeAg will be randomized into two groups according to the ratio of 2:1. 240 subjects will receive the 10 mcg experimental vaccine and 120 subjects will receive 10 mcg control vaccine respectively. Stratified 3: There are 1200 neonates born to the mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb will be randomized into 3 groups. 600 of them will receive the 10mcg experimental vaccine. 300 subjects will receive 10mcg control vaccine. And the other 300 subjects will receive 5mcg control vaccine. All these neonates will have the vaccination within 24 hours after born. The recombinant hepatitis B vaccine will be administered at m0, 1 and 6. Following each immunization, safety will be measured by assessment of adverse events through 30 days following each vaccination, serious adverse events and new-onset chronic medical conditions through 6 months post the final vaccination (Day 180 after last vaccination). For the immunogenicity testing will apply the chemiluminescence immunoassay on serum obtained on the day 0, 210 and 360 after born.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Virus Disease, DNA Virus Infections, Hepadnaviridae Infections
Keywords
safety, immunogenicity, HBV vaccine, perinatal transmission

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1740 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A1
Arm Type
Experimental
Arm Description
health neonates born to mother with positive for both HBsAg and e antigen
Arm Title
A2
Arm Type
Active Comparator
Arm Description
health neonates born to mother with positive for both HBsAg and e antigen
Arm Title
B1
Arm Type
Experimental
Arm Description
health neonates born to a mother positive for HBsAg, negative for the hepatitis B e antigen
Arm Title
B2
Arm Type
Active Comparator
Arm Description
health neonates born to a mother positive for HBsAg, negative for the hepatitis B e antigen
Arm Title
C1
Arm Type
Experimental
Arm Description
health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb
Arm Title
C2
Arm Type
Active Comparator
Arm Description
health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb
Arm Title
C3
Arm Type
Placebo Comparator
Arm Description
health neonates born to mother with negative for the HBsAg and HBeAg and HBeAb and HBcAb
Intervention Type
Biological
Intervention Name(s)
Experimental recombinant hepatitis B vaccine, HBIG
Intervention Description
Experimental 10mcg/0.5 ml recombinant hepatitis B vaccine and 200IU HBIG
Intervention Type
Biological
Intervention Name(s)
Active Comparator hepatitis B vaccine
Intervention Description
Active Comparator 10mcg/0.5 ml of recombinant hepatitis B vaccine，200IU HBIG
Intervention Type
Biological
Intervention Name(s)
Experimental recombinant hepatitis B vaccine
Intervention Description
Experimental 10mcg/0.5 ml of recombinant hepatitis B vaccine
Intervention Type
Biological
Intervention Name(s)
Active Comparator recombinant hepatitis B vaccine.
Intervention Description
Active Comparator 10mcg/0.5 ml of recombinant hepatitis B vaccine.
Intervention Type
Biological
Intervention Name(s)
Placebo Comparator recombinant hepatitis B vaccine
Intervention Description
Placebo Comparator 10mcg/0.5 ml of recombinant hepatitis B vaccine.
Primary Outcome Measure Information:
Title
The immunogenicity of experimental recombinant HBV vaccines in healthy neonates on day 210
Description
Immunogenicity testing will be chemiluminescence immunoassay on serum obtained on day 210 after first dose
Time Frame
on day 210 after the first dose
Title
The immunogenicity of experimental recombinant HBV vaccines in healthy neonates on day 360
Description
Immunogenicity testing will be chemiluminescence immunoassay on serum obtained on day 360 after first dose
Time Frame
on day 360 after the first dose
Secondary Outcome Measure Information:
Title
To evaluate the safety of recombinant HBV vaccines in the health neonates after first dose
Description
assessment of adverse events through 30 days following first dose
Time Frame
within the first 30 days after first dose
Title
To evaluate the safety of recombinant HBV vaccines in the health neonates after second dose
Description
assessment of adverse events through 30 days following second dose
Time Frame
within the first 30 days after second dose
Title
To evaluate the safety of recombinant HBV vaccines in the health neonates after third dose
Description
assessment of adverse events through 30 days following third dose
Time Frame
within the first 30 days after third dose

10. Eligibility

Sex
All
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A group (A1-A2)Subjects born to a mother positive for both HBsAg and hepatitis B e antigen. • Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age) • Subjects with a 5-minute Apgar score ≥ 7. • Subjects with temperature <37.1°C on axillary setting • Subjects with a birth weight ≥ 2.5 kg. • Normal neonatal jaundice. Written informed consent obtained from the parent(s) of the subject. Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol. B group(B1-B2) Subjects born to a mother positive for HBsAg, but negative for the hepatitis B e antigen. • Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age) • Subjects with a 5-minute Apgar score ≥ 7. • Subjects with temperature <37.1°C on axillary setting • Subjects with a birth weight ≥2.5 kg. • Normal neonatal jaundice. • Written informed consent obtained from the parent(s) of the subject. • Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol C group（C1-C3）Subjects born to a mother negative for HBsAg, hepatitis Be Antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e-antigen. Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 1 day of age) Subjects with a 5-minute Apgar score ≥ 7. Subjects with temperature <37.1°C on axillary setting Subjects with a birth weight ≥ 2.5 kg. Normal neonatal jaundice. Written informed consent obtained from the parent(s) of the subject. Subjects who the investigator believes that their parent(s) can and will comply with the requirements of the protocol. Exclusion Criteria: A group (A1-A2) Subjects born to a mother positive for both HBsAg and e Antigen. Exclusion criteria for the first shot • Subjects born to a mother positive for antibody to HBsAg. • Family history of seizures or progressive neurological disease. • Family history of congenital or hereditary immunodeficiency. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy. • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period. • Born to a mother known or suspected to be positive for HIV. Family history of congenital or hereditary immunodeficiency. Children in care. Neonatal jaundice requiring systemic treatment. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Major congenital defects or serious chronic illness, including perinatal brain damage. Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots Dysgenopathy Any reaction or hypersensitivity to the hepatitis B vaccines. Acute infections History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives B group (B1-B2) Subjects born to a mother positive for HBsAg, but negative for the hepatitis B e antigen. Exclusion criteria for the first shot • Subjects born to a mother positive for antibody to HBsAg or e antigen. • Family history of seizures or progressive neurological disease. • Family history of congenital or hereditary immunodeficiency. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy. • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period. • Born to a mother known or suspected to be positive for HIV. • Family history of congenital or hereditary immunodeficiency. • Children in care. • Neonatal jaundice requiring systemic treatment. • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. • Major congenital defects or serious chronic illness, including perinatal brain damage. • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots • Dysgenopathy • Any reaction or hypersensitivity to the hepatitis B vaccines. • Acute infections History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. 3 C group (C1-C3) Subjects born to a mother negative for HBsAg, hepatitis Be Antigen, antibody to hepatitis B core antigen, antibody to hepatitis B e-antigen. Exclusion criteria for the first shot • Subjects born to a mother positive for antibody to HBsAg, or e antigen, or antibody to B core antigen or antibody to hepatitis B e-antigen. • Family history of seizures or progressive neurological disease. • Family history of congenital or hereditary immunodeficiency. • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. • Subjects born to a mother had administrated of immunoglobulins and/or any blood products during the pregnancy. • Use of any investigational or non-registered product other than the study vaccines since birth, or planned use during the study period. • Born to a mother known or suspected to be positive for HIV. • Family history of congenital or hereditary immunodeficiency. • Children in care. Neonatal jaundice requiring systemic treatment. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Major congenital defects or serious chronic illness, including perinatal brain damage. Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third shots Dysgenopathy Any reaction or hypersensitivity to the hepatitis B vaccines. Acute infections History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives
Facility Information:
Facility Name
Jiangsu Provincial Center for Diseases Control and Prevention
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
22662137
Citation
Zhu FC, Liang ZL, Meng FY, Zeng Y, Mao QY, Chu K, Song XF, Yao X, Li JX, Ji H, Zhang YJ, Li L, Pan HX, Xu K, Dai WM, Zhang WW, Deng F, Wang H, Wang JZ. Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants. PLoS One. 2012;7(5):e37206. doi: 10.1371/journal.pone.0037206. Epub 2012 May 25.
Results Reference
derived

Learn more about this trial

The Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Health Neonates

We'll reach out to this number within 24 hrs