Elsevier

Vaccine

Volume 20, Issues 5–6, 12 December 2001, Pages 826-837
Vaccine

Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation

https://doi.org/10.1016/S0264-410X(01)00397-8Get rights and content

Abstract

In a randomized, double blinded study, 23-valent pneumococcal polysaccharide vaccine (PSV) or conjugate Haemophilus influenzae type b (HbOC) vaccine was administered to 60 healthy women in the third trimester of gestation. Total IgG, IgG1, and IgG2 antibodies to pneumococcal serotypes 6B, 14, 19F and 23F were measured by ELISA in mothers prior to immunization, at delivery and 7 months after delivery, and in infants at birth (cord blood), 2 and 7 months after delivery. IgA was evaluated in breast milk at 2 and 7 months, and opsonophagocytic activity in cord blood. PSV was safe and immunogenic in pregnant women. Transplacental transmission of vaccine-specific antibodies was efficient. Maternal immunization with PSV resulted in significantly higher concentrations of pneumococcal antibodies in infants at birth and at 2 months of age, and greater functional opsonophagocytic activity of passively acquired IgG antibody.

Introduction

Streptococcus pneumoniae is the leading cause of invasive bacterial infections in young children throughout the world [1], [2], causing bacteremia, meningitis, pneumonia, otitis media, sinusitis, and other complications of respiratory tract infections. The rate of infection is greater for children under 2 years of age, reaching rates as high as 228 cases per 100,000 in those 6–12 months old [1], [2], [3]. The greatest mortality is observed in children with invasive disease, where case fatality rates are as high as 15–20% [1], [2]. The development of resistance to antimicrobials in as much as 35% of S. pneumoniae isolates in some regions [4] adds to the difficulty of treatment of diseases caused by this organism, and emphasizes the need for a preventive approach.

Until recently, vaccines available to prevent S. pneumoniae infection and disease in children in the US were the 14- or 23-valent pneumococcal polysaccharide vaccines, both relatively poorly immunogenic and not licensed for use in children less than 2 years of age [3]. A seven-valent protein–polysaccharide conjugate pneumococcus vaccine is now approved and recommended in the US for immunization of infants in the first year of life, beginning as early as the second month of life [5], [6]. Routine utilization of this vaccine could substantially reduce the impact of pneumococcal disease in immunized children [3], but is unlikely to have a direct effect in the morbidity and mortality of the youngest infants, particularly those under 3 months of age. Other populations at risk are non-immunized infants and those for whom the conjugate vaccine is not available, as in most countries in the developing world [3], [7]. In these circumstances, immunization of women during pregnancy with the pneumococcal polysaccharide vaccine is a potential alternative approach to provide protection to young infants [8], [9], [10], [11]. The broader serotype coverage provided by the polysaccharide vaccine is an additional advantage of this strategy for both the mother and infant.

The objectives of this trial were to determine the safety and immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in healthy women during pregnancy and their offspring, to determine the transplacental transmission of antibodies to infants at the time of delivery, and to assess the persistence of antibody in infants in the first year of life. In addition, we explored the effect of maternal immunization on the production of vaccine-specific antibodies in breast milk and in the acquisition of nasal carriage of pneumococci in infants. The immunogenicity of the comparison vaccine, conjugate Haemophilus influenzae type b vaccine, was also studied and will be reported separately.

Section snippets

Patients

This was a prospective, double blind, randomized, controlled trial enrolling 60 healthy women in the third trimester of an uncomplicated pregnancy between March 1995 and June 1996. Women 19 to 39 years of age were evaluated by collaborating private obstetricians in Houston, Texas, and enrolled if their pregnancy was singleton and uneventful, after informed consent was obtained. The protocol was reviewed and approved by the Baylor Institutional Review Board and by the Review Boards of all the

Demographics

Women in the PSV and HbOC vaccine groups were similar in age (30.2 and 31.6 years, respectively), gestational age at the time of immunization (mean 33.3 and 33.0 weeks, respectively), interval between immunization and delivery (43.6 and 44.0 days, respectively), and gestational age at the time of delivery (39.4 and 39.2 weeks, respectively). The interval between immunization and delivery was greater than 2 weeks in all subjects, and 6.3 weeks on average for each group. Most women (65% PSV and

Maternal antibody response

The GMCs of maternal IgG antibody to pneumococcal serotypes 6B, 14, 19F, and 23F were significantly higher at delivery in the PSV group when compared to controls (Table 2). Among PSV vaccine recipients, a greater than two-fold increase in antibody concentrations from pre-immunization titers was observed in 65% of women to serotype 6B, 55% to serotype 14, 50% to serotype 19F, and 60% to serotype 23F. The average rise in antibody concentration for each serotype ranged between 3- and 10-fold when

Opsonophagocytosis

Infants of women who received the PSV during gestation had significantly higher titers of functional opsonic antibody to pneumococcal serotypes 6B, 14 and 19F at birth when compared to controls (Table 4). Opsonophagocytosis for serotype 23F was not determined because it was not expected to provide additional information. The correlation of cord blood antibody levels and opsonophagocytosis was determined to study the biologic activity of antibody transmitted to the infants. A significant

Breast milk antibody

Pneumococcal IgG and IgA antibodies against serotypes 6B, 14, 19F and 23F were determined in breast milk samples from nursing mothers at 2 and 7 months after delivery. The number of breast milk specimens available for analysis in the HbOC vaccine groups was proportionally larger than for the PSV group. GMCs of breast milk IgA to all serotypes studied were significantly higher in PSV recipients than in HbOC recipients at 2 months after delivery (Fig. 4). Levels of IgA remained higher in PSV

Nasal carriage of pneumococci

Nasal washes for pneumococcal carriage were obtained in 56/60 (93%) infants between 2 and 15 months of age, with a mean of 1.6 nasal washes per child. In the first 7 months of life, pneumococci were detected in 2/34 (6%) cultures from 18 infants whose mothers received PSV and in 14/70 (19%) cultures from 38 infants whose mothers received HbOC (P=0.12). None of the infants born to PSV recipients and 3/36 (8%) of infants of HbOC vaccines were colonized at 2 months of age (P=0.59). By the seventh

Discussion

Immunization during pregnancy is a strategy that takes advantage of a unique opportunity to provide young infants protection from pathogens. The efficacy of this approach and the significant benefit to both the mother and infant, have been repeatedly demonstrated worldwide with the success of maternal immunization with tetanus toxoid for the prevention of neonatal tetanus [16]. H. influenzae type b vaccines (capsular polysaccharide alone, in conjugation with diphtheria or tetanus toxoids, or

Acknowledgements

The authors gratefully acknowledge the women and infants who participated in this study; the staff at the obstetric practices of Drs. Maccato, Pinell and Thompson; the staff at the local hospitals where deliveries occurred; the pediatricians at Kelsey Seybold Clinic and other local private groups that collaborated with the infants’ care and follow-up; and the nurses, physician assistants, laboratory technicians, and administrative staff at the Baylor Influenza Research Center Unit, for their

References (41)

  • S. Black et al.

    Efficacy safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children

    Pediatr. Infect. Dis. J.

    (2000)
  • K. Mullholand et al.

    The WHO Young Infants Study Group. Bacterial etiology of serious infections in young infants in developing countries: results of a multicenter study

    Pediatr. Infect. Dis. J.

    (1999)
  • F. Vincent-Ballereau et al.

    Pneumococcal vaccination of the pregnant woman in Africa and passive immunity of the child. Immunologic control by the ELISA method

    Pathol. Biol. (Paris)

    (1985)
  • M.H. Nahm et al.

    A modified Farr assay is more specific than ELISA for measuring antibodies to Streptococcus pneumoniae capsular polysaccharides

    J. Infect. Dis.

    (1996)
  • M.H. Nahm et al.

    Identification of cross-reactive antibodies with low opsonophagocytic activity for Streptococcus pneumoniae

    J. Infect. Dis.

    (1997)
  • J.V. Madassery et al.

    IgG2 subclass deficiency: IgG subclass assays and IgG2 concentrations among 8015 blood donors

    Clin. Chem.

    (1988)
  • National Vital Statistics Reports. Centers for Disease Control and Prevention, National Center for Health Statistics....
  • World Health Organization. Neonatal Tetanus. Progress toward the global elimination of neonatal tetanus, 1990–1997. WHO...
  • M.S. Amstey et al.

    Fetal-neonatal passive immunization against Haemophilus influenzae type b

    Am. J. Obstet. Gynecol.

    (1985)
  • W.P. Glezen et al.

    Maternal immunization with the capsular polysaccharide vaccine for Haemophilus influenzae type b

    J. Infect. Dis.

    (1992)
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    This study was presented in part at the 37th Annual Meeting of the Infectious Diseases Society of America, November 1999, Philadelphia, PA, Abstract no. 639. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government.

    1

    Present address: Section of Infectious Diseases, Department of Pediatrics, University of Chicago, Chicago, IL, USA.

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