Pediatr Infect Dis J, 2001;20:931–40 Vol. 20, No. 10 Copyright © 2001 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. Safety and antibody persistence following Haemophilus influenzae type b conjugate or pneumococcal polysaccharide vaccines given before pregnancy in women of childbearing age and their infants MATHURAM SANTOSHAM, MD, MPH, JANET A. ENGLUND, MD, PAMELA MCINNES, DDS, MSC(DENT), JANNE CROLL, MPAS, PA-C, CLAUDETTE M. THOMPSON, BS, LARRY CROLL, RPH, W. PAUL GLEZEN, MD AND GEORGE R. SIBER, MD Background. Immunization of healthy women before pregnancy is a potential approach to pro- viding increased levels of maternal antibody to newborns to protect them from infections occur- ring during the perinatal period and first months of life. Methods. Healthy nonpregnant Pima Indian women of childbearing age were randomized to receive one of two Haemophilus influenzae type b (Hib) conjugate vaccines [HbOC or Hib- meningococcal outer membrane protein complex (OMP)] or a 23-valent pneumococcal polysaccha- ride vaccine (PnPs). Infants received Hib-OMP vaccine at 2, 4 and 12 months of age. Vaccine safety and immunogenicity was evaluated in the women and their infants. Results. Anti-polyribose ribitol phosphate anti- body titers were significantly higher in women in both Hib conjugate vaccine groups than in the pneumococcal vaccine group throughout the 37- month observation period. Antibody responses to HbOC vaccine were significantly higher than those to Hib-OMP. A subsequent booster dose of each Hib conjugate vaccine induced reactions and antibody responses similar to those of the first dose. Infants born to mothers immunized with Hib vaccines compared with PnPs had sig- nificantly higher polyribose ribitol phosphate- specific IgG antibody titers at birth and 2 months of age but lower antibody responses to Hib-OMP at 6 months and similar titers before and after boosting with Hib-OMP at 1 year of age. By contrast women immunized with PnPs did not have significantly elevated concentrations of pneumococcal-specific antibody at delivery, and their infants had pneumococcal antibody titers similar to those of infants born to mothers who did not receive pneumococcal vaccine before pregnancy. Conclusion. Hib conjugate vaccine given to women before pregnancy significantly increased the proportion of infants who had protective Hib antibody levels at birth and 2 months of age. INTRODUCTION Several approaches may be considered to help pre- vent serious infections that may occur during the perinatal period or early infancy. For example univer- sal childhood immunization has effectively eliminated congenital disease caused by rubella. Protection may be induced at birth by active immunization of the infant against etiologic agents such as tuberculosis and hepatitis B. However, active immunization at birth has generally not resulted in an early protective response to most vaccine antigens, including diphtheria, teta- nus, pertussis and Haemophilus influenzae type b (Hib). 1–3 Active immunization of neonates has even been noted to suppress antibody responses to immuni- zation against H. influenzae type b later in infancy. 4, 5 Another approach to protect neonates is passive immu- nization with human immunoglobulin or monoclonal antibodies. 6 This approach has been used successfully Accepted for publication May 16, 2001. From the Department of International Health, Center for American Indian and Alaskan Native Health, Johns Hopkins University, Baltimore, MD (MS, JC, LC); the Department of Pediatrics, University of Chicago, Chicago, IL (JAE); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (PM); the Dana-Farber Cancer Insti- tute, Boston, MA (CMT); the Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX (WPG); and Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY (GRS). Key words: Antibody, Haemophilus influenzae type b conju- gate vaccine, pneumococcal polysaccharide vaccine, prepregnancy vaccination. Address for reprints: Dr. Mathuram Santosham, Johns Hop- kins University School of Hygiene and Public Health, 615 N. Wolfe Street, B Suite E8132, Baltimore, MD 21205. Fax 410-614- 1419; E-mail msantosh@jhsph.edu. 931