Protective Efficacy of Flublok® Quadrivalent Versus Licensed Inactivated Influenza Vaccine in Adults ≥50 Years of Age

The goal of this study is to establish that Flublok Quadrivalent is non-inferior to fully
licensed (traditional approval status) quadrivalent inactivated influenza vaccine (IIV4) in
protecting against laboratory-confirmed clinical influenza disease in the ≥50 year age
population. Real-time Polymerase Chain Reaction (rtPCR) will be used to confirm influenza
infection and to type the strains involved, as molecular methodologies have been demonstrated
to be more sensitive than other more traditional methodologies, e.g. culture. For
rtPCR-positive clinical samples, reserved aliquots will be processed for culture, so that
antigenic similarity to the HA present in study vaccines can be tested.

In various clinical studies the investigators demonstrated that the immune response against
the influenza A viruses is improved as a result of the higher hemagglutinin content.
Furthermore, influenza virus disease and hospitalization associated with influenza-related
illness in older adults (> 50 years) was considerably reduced (90%) following vaccination
with TIV, even though the circulating influenza A strain was antigenically dissimilar to that
in the vaccine. However, more recently Skowronski et al. reported that the low influenza
vaccine effectiveness in 2012-2013 was not associated with antigenic drift but was instead
related to mutations in the egg-adapted H3N2 vaccine strain. Flublok manufactured using
recombinant technology does not contain the mutations responsible for the reported lower
effectiveness and may thus offer improved protection when mutations such as those described
are induced in the process of adapting the influenza virus to growth in eggs.

Inclusion Criteria:

1. Ambulatory adults aged 50 and older.

2. Medically stable, as determined by medical history and targeted physical examination.
"Medically stable" is defined as no change in diagnoses or chronic medications (dose
or class) for medical reasons in the 3 months prior to study.

3. Absence of underlying conditions that make participation in the study contrary to the
subject's best interest.

4. Able to understand and comply with planned study procedures.

5. Provides written informed consent prior to initiation of any study procedure.

Exclusion Criteria:

1. Known contraindication to either study vaccine (see product package inserts)

2. Receipt of any other influenza vaccine within 180 days prior to enrollment in this
study.

3. Underlying disease or ongoing therapy that might cause immunocompromise, e.g.
cytotoxic agents or supraphysiologic doses of corticosteroids, such that response to
vaccination might be sub-optimal.