H1N1 Vaccine in Pregnant Women

Recently, a novel swine-origin influenza A/H1N1 virus was identified as a significant cause of febrile respiratory illnesses in Mexico and the United States. It rapidly spread to many countries around the world, prompting the World Health Organization to declare a pandemic on June 11, 2009. Data from several cohorts in different age groups that received licensed trivalent seasonal influenza vaccines suggest that these vaccines are unlikely to provide protection against the new virus. In addition, adults are more likely to have measurable levels of serum hemagglutination inhibition assay (HAI) or neutralizing antibody than are children. These data indicate the need to develop vaccines against the new H1N1 strain and suggest that different vaccine strategies (e.g., number of doses, need for adjuvant) may be appropriate for persons in different age groups. Pregnant women are at an increased risk for the complications of influenza. A higher dose or multiple doses of an unadjuvanted, inactivated influenza H1N1 vaccine may be necessary to confer protection to this at risk population. This protocol will explore the antibody response following vaccination of pregnant women at 2 different dose levels (15 mcg and 30 mcg). The 2 doses of inactivated influenza H1N1 vaccine will be administered 21 days apart. This study will assess the immune response following a single dose of H1N1 vaccine, to assess whether individuals have any pre-existing "prime" immunity, such that the initial H1N1 vaccination serves as a boost, thus conferring a more rapid time to protection with the need for fewer doses. Antibody responses will be assessed 21 days after each dose. The primary objectives are: safety, to assess the safety of unadjuvanted, inactivated H1N1influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose; and immunogenicity, to assess the antibody response following a single dose of unadjuvanted, inactivated H1N1 influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose. The secondary objectives are to: assess the antibody response following 2 doses of unadjuvanted, inactivated H1N1 influenza vaccine in pregnant women when administered at the 15 mcg or 30 mcg dose; and assess the efficiency of placental transport of maternal influenza antigen specific antibodies to the neonate. This is a randomized, double-blinded, phase II study in 120 pregnant women, ages 18-39 years. Subjects will be randomized into 2 groups (60 pregnant women per dose group) to receive intramuscular inactivated influenza H1N1 vaccine at 15 mcg (Group 1) or 30 mcg (Group 2) on Days 0 and 21. Following immunization, safety will be measured by assessment of adverse events through 21 days following the last vaccination (Day 42), serious adverse events and new-onset chronic medical conditions through 7 months post first vaccination (Day 201). Reactogenicity to the vaccine will be assessed for 8 days following each vaccination (Day 0-7). Immunogenicity testing will include HAI and neutralizing antibody testing on serum obtained on Days 0, 21 and 42. This includes samples collected prior to each vaccination and samples collected 21 days following each vaccination. HAI antibody testing will be also be performed on serum from maternal and cord blood collected at delivery.