Influenza Vaccine in Pregnant Women

Influenza is a significant cause of morbidity and mortality in the United States (US), resulting in an average of 226,000 hospitalizations and 36,000 deaths each year. Pregnant women and infants are at an increased risk for the complications of influenza. Severe disease, emergency department visits and hospitalizations occur frequently in pregnant women and infants which are considered high risk populations. In the US, routine vaccination with inactivated trivalent influenza vaccine (TIV) is recommended for pregnant women or those who deliver during the influenza season. Few studies exist on the safety and immunogenicity of administration of seasonal inactivated TIV despite long-standing recommendations. Although influenza vaccination has been recommended during pregnancy, the rates of immunization remain low, at about 13 percent. This is a multi-site randomized, double-blind clinical trial in 200 ambulatory, medically stable 18-39 year old, inclusive, pregnant women in their second or third trimester of pregnancy (from 14 weeks of gestation to term, inclusive). Study subjects will be randomized 1:1 to receive one dose of a 2008-2009 seasonal inactivated TIV, either Fluzone® or Fluarix® (100 pregnant women per vaccine group). Once enrolled, a blood sample will be collected and each subject will receive a single 0.5 mL dose of a 2008-2009 seasonal inactivated TIV, either Fluzone® or Fluarix®. The vaccination will occur on Day 0. Subjects will be observed for approximately 15 minutes after vaccination. All subjects will maintain a memory aid recording oral temperature, and systemic and local adverse events (AEs) for 7 days after each vaccination. Subjects will be encouraged to take their temperature around the same time each day. Subjects will have a phone call on Day 2 for review of memory aid, concomitant medication assessment, and assessment of AEs. Subjects will have a phone call on Day 8 for AE assessment, concomitant medication assessment and review of memory aid. At approximately Day 28 after the vaccination, subjects will return to the clinic for immunogenicity blood sample collection, concomitant medication assessment, and assessment of any AEs. A targeted physical exam will be conducted, if indicated. At approximately Day 180 or 6 months after vaccination, subjects will have a phone call for assessment for any serious adverse events (SAEs). Unsolicited non-serious AE data will be captured Day 0 through Day 28. Maternal SAE data will be captured throughout the study period (Day 0 through Day 180, approximately 6 months after dose of vaccine). Maternal and infant SAE data will be collected when obtaining data on pregnancy outcome. Serum for immunogenicity evaluations will be obtained prior to the dose of vaccine (at Day 0); and one month after vaccination (at Day 28). Pregnancy outcome data will be captured by a review of medical records and a phone call to the subject. Data include any complications during labor and delivery for both the mother as well as the neonate, to include premature delivery or delivery by emergency cesarean section. Neonatal assessments will include but not be limited to gestational age, birth weight, Apgar scores, congenital abnormalities, infection, hematological and metabolic complications, admission to nursery or Neonatal Intensive Care Unit and the need for respiratory support. Blood samples collected will be tested in a central laboratory for the levels of hemagglutination inhibition (HAI) and microneutralization (MN) antibodies.