Impact of Metabolic Syndrome on Flu Vaccine Efficacy

The development of industrialization with increased food consumption and sedentarity has
given rise to an obesity pandemic, which affects up to 30% of the population in countries
like US, these populations being at greater risk for cardiovascular diseases, and diabetes.
More than obesity per se, visceral obesity is associated with metabolic diseases that cluster
together and clinically defined metabolic syndrome. MetS comprises individuals with at least
three of the 5 of the following factors: abdominal obesity, high blood triglycerides, low HDL
("good cholesterol"), high blood pressure and elevated fasting glucose. Metabolic syndrome is
associated with a low-grade inflammation characterized by an infiltration of immune cells
particularly in the adipose tissue, the liver and the pancreas that is thought to be
responsible for the induction of insulin resistance. It is thought that obesity predisposes
to other diseases such as cancer, asthma but only little attention has been given to
infectious diseases. Studies have shown that obesity increases the risk of severe influenza
infection and associated death and reduces the efficacy of influenza vaccine in the obese
population but yet, the molecular mechanisms have not been described. Immune dysfunctions
associated with obesity are suspected to play a major role but obesity is often associated
with respiratory disorders that could directly explain the increased susceptibility to
influenza infection. Also, metabolically healthy obesity is less associated with
inflammation. Therefore, the investigators would like to focus particularly on metabolic
syndrome, and determine how it influences immune response to viruses.

The investigators are thus hypothesizing that differences in the innate immune responses
between individual with or without metabolic syndrome impact viral infection and vaccine
outcome. Recent studies involving complex biological analysis and computational modeling have
shown that the ability of an individual to positively respond to influenza vaccine can be
molecularly predicted by looking at markers in the blood cells. The investigators will
perform seasonal influenza vaccination in people with or without metabolic syndrome to
determine if the late adaptive response assessed by antibodies titers is different between
the two groups and correlates with the early immune response assessed by gene expression
profile in whole blood cells.

Healthy nutritional habits along with increased physical activities should be best at
preventing the development of metabolic syndrome but socio-economical issues are slowing the
implementation of these changes. Therefore, as metabolic syndrome is raising public health
concerns, it is important to understand why the metabolic syndrome affects susceptibility to
diseases.

Inclusion criteria for the METABOLIC SYNDROME COHORT( Participants must have 3 or more of
the following 5 risk factors):

- Abdominal Obesity, given as a waist circumference: Men >102 cm (>40 in) Women > 88 cm
(>35 in)

- Triglycerides >150 mg/dl

- HDL Cholesterol: Men < 40 mg/dl Women < 50 mg/dl

- Blood Pressure >130/ >85 mm Hg - or controlled on antihypertensive medication

- Fasting Glucose > 100 mg/dl

Inclusion criteria for the HEALTHY CONTROLS (Participants must have all of the requirements
below) :

- body mass index 18.5 - 25 kg/m2

- HDL female > 50 mg/dL, male > 40 mg/dL

- fasting glucose < 100 mg/dL

- triglycerides <150 mg/dL,

- waist circumference of a female < 88 cm, male < 102 cm)

- - Blood pressure < or = to 120/80 (based on an average of 3 readings taken 5 minutes
apart after the consent form has been signed)

Exclusion criteria :

- Currently undergoing treatment for the metabolic syndrome

- The average of 2 BP readings > 150/90 (based on 2 B/Ps taken at screening visit 1).

- Hepatitis A, B and C

- NSAIDs and/or Aspirin ingestion within the last 14 days

- Self-reported history of any active autoimmune diseases

- Self-reported ingestion of statins within the last 3 months

- Self-reported antibiotic use within the last 3 months

- Anti-inflammatory drugs including biologics and corticosteroids within last 3 months(
nasal spray and topical applications are OK)or Omega 3 Fatty Acids.

- Self-reported hx of cancer treatment within the last year

- Allergy to eggs

- History of Guillain-Barre syndrome

- Pregnant ( determined by point of care testing at screening visit 1).

- HIV positive

- Self-reported history of flu vaccination within the past 3 months.

- Any self-reported infection in the week of the visit except the first two visits
(Screening visit 1 and Screening visit 2) and the last visit (Study visit #5) that
could be rescheduled.

- Any medical, psychological or social condition that, in the opinion of the
Investigator, would jeopardize the health or well-being of the participant during any
study procedures or the integrity of the data.

Study Population Description The population from which the groups will be selected are
resident of New York City.