2010-2011 Trivalent Influenza Vaccine (TIV) in Pregnant Women

Influenza is a significant cause of morbidity and mortality in the United States. Pregnant
women and infants are at an increased risk for the complications of influenza. Pregnant
women are considered a high risk population. In the United States, routine vaccination with
inactivated trivalent influenza vaccine (TIV) for women who are pregnant or deliver during
the influenza season is recommended. However, few studies exist on the safety and
immunogenicity of administration of seasonal inactivated TIV. Although influenza vaccination
has been recommended during pregnancy, the rates of immunization remain low, at about 13
percent, which partly reflects concern of safety among pregnant women and providers. It is
important to gather prospective data on the safety and immunogenicity of inactivated TIV
vaccine in pregnant women. This is a multi-site randomized, double-blinded clinical trial in
180 healthy 18-39 year old, pregnant women in their second or third trimester of pregnancy
(from 14 weeks of gestation to 33 weeks/6 days gestation, inclusive) and 60 healthy 18-39
year old non-pregnant controls. Study subjects will be randomized 1:1:1 to receive one of
the following three 2010-2011 seasonal inactivated trivalent influenza vaccines: Fluarix®,
Agriflu®, or Fluzone® (60 pregnant women and 20 non-pregnant women per group). The study
will begin enrollment when at least 2 of the 4 study products are available. Once enrolled,
a blood sample will be collected and each subject will receive a single 0.5 mL dose of the
assigned vaccine. Subjects will be observed for at least 15 minutes after immunization, and
the subjects will maintain a memory aid to record oral temperature and systemic and local
adverse events (AEs) for 8 days after immunization. Subjects will have a phone call on Day 2
and 8 for review of memory aid, concomitant medication assessment, and assessment of AEs. At
approximately Day 28 post-vaccination, subjects will return to the clinic for blood sample
collection, AE and concomitant medication assessment, and a targeted physical examination
(if indicated). Pregnant subjects will also have scheduled phone calls from Day 28 until the
time of delivery or Day 180, whichever is later, to assess for any new-onset chronic medical
conditions, and pregnancy-related problems such as miscarriage or serious adverse events
(SAEs) since the last visit. At approximately Day 180 post-vaccination, subjects will return
to the clinic for blood sample collection and assessment of the receipt of any vaccines
since the last visit. Subjects will be asked about any new-onset chronic medical conditions,
SAEs since the last visit and pregnancy-related problems such as miscarriage (for the
pregnant women cohort). The duration of the study will be approximately 6 months for the
non-pregnant subjects and about 6-8 months for the pregnant subjects, depending on delivery
date for the pregnant women. Pregnant subjects will have collection of maternal and cord
blood at the time of delivery. Pregnant subjects will also have a phone call 1 month after
delivery to assess for any new-onset chronic medical conditions or SAEs since the last
visit. The primary objectives are to evaluate the safety of a single 0.5 mL intramuscular
injection of the 2010-2011 inactivated TIV in pregnant women and to evaluate the
immunogenicity of the 2010-2011 inactivated TIV in pregnant women by hemagglutination
inhibition assay (HAI). The secondary objectives are to evaluate the persistence of
antibodies to the 2010-2011 inactivated TIV in pregnant women at Day 180 and to assess the
transfer of maternally derived antibody against viruses in the 2010-2011 inactivated TIV to
infants born to mothers vaccinated with 2010-2011 inactivated TIV.