MATERNAL IMMUNIZATION TO PREVENT INFANT OTITIS MEDIA

DESCRIPTION (provided by applicant): Vaccine strategies to prevent childhood otitis media (OM) are being sought due to its major public health impact and the troubling increase in antibiotic resistant bacteria. The pneumococcus bacteria is a prime target for vaccine prevention. Maternal immunization is a strategy designed to prevent early infant OM, since it is one of the greatest risk determinants for recurrent and chronic OM. A recently licensed 7-valent pneumococcal conjugate vaccine (PCV7) is now given routinely to all infants beginning at age 2 months. This vaccine is highly protective against invasive pneumococcal disease after 7 months of age, has modest (6-9%) protection against all OM episodes between 7 and 24 months, and a 57% reduction in vaccine-type pneumococcal AOM. But it does not significantly reduce OM before 7 months. Thus, there remains a potentially important role for maternal pneumococcal immunization to prevent pneumococcal AOM in the first 6 months of life. Thus, it is important to test the hypothesis that maternal pneumococcal immunization during pregnancy does not produce immune interference in the infant, impairing response to the infant vaccine, before proceeding with a maternal vaccine OM efficacy trial. This Phase I/II trial will enroll 154 pregnant women and follow subjects and their infants to age 13 months. Primary aims are: (1) to determine if infants of women immunized with 9-valent PCV (PCV9) and infants of control women who receive placebo during the third trimester of pregnancy have equivalent anti-capsular polysaccharide (PS) IgG antibody responses to PCV7 measured one month after the third vaccine injection at 6 months of age, and (2) to compare local and systemic adverse events among women immunized with PCV9 or placebo. We will also investigate the hypotheses that (1) maternal immunization does not interfere with the infant's antibody subclass and pneumococcal opsonic responses to the primary PCV7 vaccine series or to booster PCV7 immunization at 12 months, (2) pregnant women have a significant antibody response to PCV9 vaccine compared to placebo vaccine and increased antibody persists 13 months after delivery, (3) anti-PS IgG and secretory IgA antibodies are present in the milk of immunized lactating women, and (4) maternal immunization does not interfere with the infants' antibody response to H. influenzae type b conjugate and diphtheria toxoid vaccines. Transplacental anti-PS IgG antibody transfer, the natural decline of two anti-PS antibodies against PS antigens in the maternal but not the infant vaccine, and the natural production of one anti-PS antibody not in either vaccine will be measured. The trial has enrolled and randomized 87 subjects to date with continuous, steady subject accrual since November 2000. Results of this trial will have a profound impact on the broad field of maternal immunization to prevent early infant disease caused by a variety of infant bacterial and viral pathogens.