Safety of Lactobacillus Rhamnosus GG Versus Placebo in Elderly Subjects Receiving Live Attenuated Influenza Vaccine

Inclusion Criteria:

1. Age 65-80 years

2. Willing to complete the informed consent process

3. Able and willing to participate for the planned duration of the study, including
availability for follow-up telephone contact

4. Is community dwelling for the past two years

5. Has received routine physical in the past two years

6. Has no new chronic conditions in the past two years

7. Identifies a primary care clinician

8. Has received recommended preventive services (Task Force for Clinical Preventive
Services) for vaccination and cancer prevention/detection, e.g.:

- Pneumococcal vaccination

- Mammography

- Screening colonoscopy for colon cancer

9. Willing to comply with protocol and report on compliance and side effects during the
study period

10. Informed consent obtained and signed prior to screening

Exclusion Criteria:

1. Vaccination with any vaccine within the one month period prior to study enrollment or
intent to receive any other vaccine during the study period, other than TIV in fall
2012

2. History of hypersensitivity to any influenza vaccine components including eggs, egg
proteins, gentamicin, gelatin or arginine

3. History of avoidance of egg and/or egg-based products for any reason, unless they
have previously received TIV or LAIV without hypersensitivity

4. History of Guillain-Barre syndrome

5. Acute febrile illness within the week prior to LAIV immunization - immunization
deferred until illness resolved

6. Consumption of supplements or food products containing LGG or probiotics for 28 days
prior to the start of the study or consumption of yogurt that has the "live and
active" cultures seal

7. Known or suspected allergies to probiotics, Lactobacillus, microcrystalline
cellulose, gelatin or antibiotics that may be used to treat LGG bacteremia or
infection (i.e., subject able to tolerate at least 2 of the following regimens -
Ampicillin or other beta lactam antibiotic, and Clindamycin, and Moxifloxacin)

8. Received oral or parenteral antibiotics within 4 weeks of enrollment or prescribed
antibiotics on the day or enrollment

9. Drug or alcohol abuse, defined as the continued use of alcohol despite the
development of social, legal, or health problems, within the previous 12 months

10. Hospitalization, major surgery or endoscopy within the last 3 months

11. Scheduled hospital admission or surgery within 3 months of enrollment

12. Resident of a nursing home or rehabilitation center

13. Close and/or household contact with severely immunocompromised persons (e.g.,
transplant recipients, cancer patients)

14. Receipt of any of the following medications within the specified time frame:

- Antiviral agents for influenza A and B in the prior 2 weeks (anti-influenza
medications are unlikely to be needed after LAIV immunization since LAIV will be
administered at the end of the influenza season, but should be prescribed if
clinically indicated)

- Immune Globulin within the prior 6 months

- Immune modulating drugs such as Belimumab, azathioprine, mercaptopurine,
methotrexate, hydroxychloroquine or leflunomide at any time or any oral or
parenteral corticosteroid in the prior 12 months

- Fingolimod at any time

- Salicylates at doses higher than 163 mg/day for primary prevention of myocardial
infarction. (Reye's Syndrome in adults is extremely rare - to our knowledge the
oldest reported patient was aged 61 and as of 1989 when Reye Syndrome was more
common, it had only been reported in 25 adults. In addition, increasing numbers
of adults are being placed on low dose aspirin for primary and secondary
prevention of cardiovascular disease, some of whom may also have influenza, but
there has been no increase in reports or Reye's Syndrome in adults.)

15. Presence of any of the following:

- Grade 2 or higher abnormal vital signs or abnormalities on physical exam during
screening or presence of any wheezing on physical exam at baseline

- Indwelling catheter or implanted hardware/prosthetic device or feeding tube

- Current or within the last 2 years, any episode of bowel leak, acute abdomen,
diverticulitis, colitis, bloody bowel movements or peptic ulcer disease,
including any surgical procedure or current prescription medications for any of
these conditions

- Current or within the last four weeks, active bowel disease such as an episode
of infectious or non-infectious diarrhea, constipation or vomiting lasting more
than 12 hours or current prescription medications for any of these conditions

- Any history of gastric or intestinal dysmotility, slowed transit time, variable
small intestinal permeability, pancreatitis, history of gastrointestinal tract
cancer or metastasis or inflammatory bowel disease or current prescription
medication for any of these conditions

- Any history of Hepatitis B or Hepatitis C infections, cirrhosis, or chronic
liver disease

- Underlying structural heart disease such as abnormal native heart valve or
congenital abnormality, previous history of endocarditis or valve replacement,
Stage IV congestive heart failure or chronic cardiovascular conditions (except
hypertension)

- History of peripheral vascular disease or stroke

- Immunosuppression including HIV positive, solid organ or stem cell transplant
recipient, receiving any oral or parenteral immunosuppressive therapy,
neutrophil count < 500/mm3, or an anticipated drop in the neutrophil count to <
500/mm3 during the 56 days post LAIV vaccination or active or planned
chemotherapy or radiotherapy

- History of collagen vascular or autoimmune disease

- History of renal disease

- History of chronic obstructive pulmonary disease or asthma

- History of neurologic or neuromuscular diseases

- History of hematologic diseases

- Diabetes or thyroid disease or metabolic disorder

- Active tuberculosis (TB), defined as undergoing a work up for suspected active
TB infection or currently on treatment for active TB or scheduled for tuberculin
test in the next 4 weeks

- Fever or acute illness or nasal congestion during the baseline visit (LAIV
administration)

16. Positive drug or alcohol testing at screening or positive breathalyzer at baseline or
an unwillingness to undergo drug and alcohol testing

17. Abnormal laboratory tests defined as any of the following:

- White blood cell (WBC)< 3.3 or > 12.0 K/microliters

- Neutrophil < 500/mm3

- Platelets < 125 K/microliter

- Hemoglobin males: < 12.0 g/dL; females: < 11.0 g/dL

- Creatinine > 1.8 mg/dL

- Blood urea nitrogen (BUN) > 27 mg/dL

- Aspartate aminotransferase (AST) > 1.25 ULN

- Alanine aminotransferase (ALT) > 1.25 ULN

- Alkaline phosphatase > 1.25 ULN

- Bilirubin (total) > 1.5 ULN

- Glucose (non-fasting) > 126 mg/dL

- Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody

18. Any other condition that in the opinion of the investigator would jeopardize the
safety or rights of the subject participating in the study or would make it unlikely
the subject could complete the study