Pneumococcal conjugate vaccines as maternal and infant immunogens: challenges of maternal recruitment

Maternal pneumococcal immunization may be a strategy for the prevention of pneumococcal disease during the first months of life before infant-administered pneumococcal conjugate vaccine (PCV) becomes protective. Preparatory to a Phase III efficacy trial to investigate this strategy for preventing early infant otitis media (OM), we are conducting a Phase I-II randomized, double-masked trial to determine if maternal 9-valent PCV immunization alters active antibody production in infants who are immunized with PCV-7 and to compare local and systemic adverse events among women immunized with PCV-9 or placebo. A pilot study was conducted in 1997 in a Minneapolis-St. Paul health maintenance organization, HealthPartners (HP), to estimate enrollment rate for the proposed Phase III trial. A total of 154 pregnant women were selected of whom 122 appeared to be eligible from ICD codes in the HP claims database; 76 responded, and 46 of these were eligible for participation. Four of the 46 reported that they would be very likely and 21 somewhat likely to participate; an estimated 20% (25/122) participation rate. The records of 4289 women in their second trimester have been reviewed to date for the Phase I/II trial; 2589 (60%) were found not to be eligible; and an additional 1015 (24%) could not be contacted. Of the 685 remaining, 558 (81%) were not interested in participating when interviewed, and 127 (19%) have consented. Most (46%) of those who declined participation have cited concern about the safety of vaccination during pregnancy. While the overall participation rate of second trimester women is only 3% (127/4289), maternal attrition (2.8%) and infant attrition from the study before age 7 months (3.9%) are lower than projected (25%). Differences in study design could explain the difference in participation rates estimated in the pilot study and experienced in the Phase I/II study. Reports of safety from large-scale studies of maternal PCV immunization in industrialized countries are needed before women are receptive to maternal immunization to protect their infants against pneumococcal disease. (C) 2003 Elsevier Science Ltd. All rights reserved.