Academic journal article Bulletin of the World Health Organization

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

Academic journal article Bulletin of the World Health Organization

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

Article excerpt

Voir page 369 le resume en francais. En la pagina 370 figura un resumen en espanol.

Introduction

Haemophilus influenzae type B (Hib) is a leading cause of invasive diseases such as meningitis, bacteraemia, epiglottitis, and pneumonia in early childhood (1-5). Vaccine-engendered antibody directed to the polyribosylphosphate (PRP) capsular polysaccharide has been shown to confer a high level of protection (6). The original purified PRP vaccines have been replaced by a variety of conjugate vaccines capable of eliciting a protective immune response in infants (4, 7-9). The safety and immunogenicity of these conjugate vaccines are well established, and their routine use in infants has resulted in a dramatic decline in the incidence of Hib disease. Recently, Hib conjugates have been combined with diphtheria--tetanus--pertussis (DTP) vaccines and administered simultaneously in a single-dose form (10, 11). This has greatly facilitated routine immunization programmes.

The vast majority of studies evaluating Hib vaccines have been conducted in developed countries. While long felt to be a pathogen primarily of temperate climates, Hib has been found to display a similar epidemiology in tropical and subtropical areas of the world (1, 12, 13). Therefore, evaluation of Hib vaccines, especially in combination with other vaccines routinely administered to infants, is warranted in developing countries where unique factors may influence the immune response to such vaccines. For example, race has been found to modulate the immune response to PRP-containing vaccines (12). Furthermore, the routine immunization of most mothers in developing countries against tetanus during pregnancy in an effort to prevent neonatal tetanus may have an impact on use of Hib conjugate vaccines. The infants of such mothers possess elevated levels of anti-tetanus toxin antibodies, which may reduce the anti-PRP antibody response via epitopic suppression.

In Thailand, [is greater than] 80% of Hib meningitis occurs within the first 2 years of life (14). Many Thai children within this age group do not possess protective levels of anti-PRP antibody at this age; however, by 4 years of age, the vast majority of them have attained protective levels of antibody, indicating that Hib circulates within this age group. Immunization of this high-risk group is clearly warranted.

The present study was conducted to determine the safety and immunogenicity of DTP vaccine combined with a PRP-tetanus toxoid (PRP-T) conjugate vaccine among 2-month-old infants born to mothers immunized against tetanus during pregnancy. We were specifically interested in determining whether high levels of pre-existing maternal anti-tetanus antibody would adversely affect the immune response to the PRP conjugate component (15). We therefore immunized a second group of infants with a licensed Hib conjugate vaccine that uses a carrier protein other than tetanus toxoid (outer-membrane proteins from group B meningococcus) and these infants served as controls.

Materials and methods

Subjects

The study was conducted at the well-baby clinic, a paediatric outpatient unit of the Udornthani Hospital, in rural north-eastern Thailand. Healthy infants aged approximately 2 months (range, 1.4-2.9 months), with no prior history of immunization against DTP or Hib were eligible for enrolment. All infants were born to mothers who were immunized against tetanus during pregnancy; the infants underwent a routine physical examination and a medical history was taken. Written informed consent was obtained from the parents. Exclusion criteria included the following: acute febrile illness, neurological or developmental disorder, history of allergies, previous immunization against DTP or Hib, treatment with immunosuppressive drugs, immunodeficiency, significant systemic illness, receipt of immunoglobulins (Igs), plasma, or whole blood since birth, or participation in another clinical trial. …

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