Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

Condition(s) targeted: Influenza

Intervention: Trivalent Seasonal Live attenuated Influenza vaccine (Biological); Seasonal Trivalent Influenza Vaccine 2010-2011 (Biological); Seasonal Influenza Vaccine TIV/LAIV (Biological); Seasonal Influenza Vaccines LAIV/TIV (Biological)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: University of Rochester

A total of 88 children between 2 and 9 years of age will be randomized to receive a two dose schedule of either licensed live attenuated trivalent seasonal influenza vaccine (LAIV) or licensed inactivated seasonal influenza vaccine (TIV)or TIV followed by LAIV or LAIV followed by TIV separated by 28 days. Children with a laboratory documented history of prior H1N1 infection will be excluded.

Official title: Evaluation of the Effect of Age and Prior Immunity on the Response to Live or Inactivated Seasonal (A/California/7/2009-like (2009 H1N1), A/Perth/16/2009-like (H3N2), and B/Brisbane/60/2008-like (B/Victoria Lineage) Influenza Vaccines in Children

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C

The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C

The primary end point for assessment of live attenuated vaccine take will be the AUC of nasopharyngeal strain-specific virus assessed by immunoperoxidase stained plaquesin MDCK cells at 33 degrees C

Secondary outcome:

The AUC of live vaccine shedding determined by quantitative rtRT-PCR

The frequency and magnitude of hemagglutinin-inhibition (HAI) IgG and IgA ELISA, and neutralizing antibody response to vaccine

The frequency and magnitude of hemagglutinin-specific mucosal IgG and IgA responses assessed by ELISA on nasal secretions

Development of specific local and systemic symptoms occurring after vaccine

The frequency and magnitude of hemagglutinin-inhibition (HAI) IgG and IgA ELISA, and neutralizing antibody response to vaccine

The frequency and magnitude of hemagglutinin-specific mucosal IgG and IgA responses assessed by ELISA on nasal secretions

Detailed description: The study will be conducted as a randomized, prospective, open-label evaluation of the clinical tolerability, vaccine virus shedding, and serum and mucosal antibody response to vaccination with either live trivalent influenza vaccine (LAIV) or trivalent influenza vaccine (TIV) in healthy children between the ages of 2 and 9 years. Children will be screened for antibody to A/Brisbane/57/07 (H1N1) and A/California/07/09 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 before and at indicated times after the start of the study. They will not be randomized based on antibody levels. Children with prior documented infection with the 2009 pandemic H1N1 virus will be excluded. Vaccine will be administered on days 0 and 28. Safety of vaccination will be assessed using symptoms collected by parents for 7 days after each dose of vaccine. Serum will be obtained prior to and on day 28 following each dose of vaccine and assessed for antibody by HAI, ELISA, and neutralization techniques. Nasal secretions will be obtained by nasal wick prior to and on day 28 after each dose and assessed for HA-specific IgA and IgG antibody by ELISA. Nasal swabs will be obtained on days 2, 4, and 7 after each dose of live vaccine and assessed for the presence and magnitude of vaccine virus shedding of the live attenuated vaccine by rtRT-PCR and TCID50 on MDCK cells.

Minimum age: 2 Years. Maximum age: 9 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Aged between 2 and 9 years, inclusive.

- No prior history of laboratory documented infection with novel H1N1 virus

- The subject must be in good health, as determined by: vital signs (heart rate <140

bpm; blood pressure: systolic ≥ 90 mm Hg and ≤140 mm Hg; diastolic ≤ 90 mm Hg; oral temperature <100. 0ºF); medical history; and targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months.

- The subject/parents are able to understand and comply with the planned study

procedures, including being available for all study visits.

- The subject/parents have provided informed consent prior to any study procedures. (An

assent will be obtained for all children as required by the institutional IRB.) Exclusion Criteria:

- Subjects with a laboratory documented history of previous novel H1N1 infection.

- History of egg allergy or allergy to other components of vaccine.

- History of wheezing.

- The subject is immunosuppressed as a result of an underlying illness or treatment

with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy.

- The subject has an active neoplastic disease.

- The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids,

or high-dose inhaled steroids (>800 mg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).

- The subject received immunoglobulin or another blood product within the 3 months

prior to enrollment in this study.

- The subject has received an inactivated vaccine within the 2 weeks or a live vaccine

within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days (or 56 days for vaccine naïve recipients).

- The subject has an acute or chronic medical condition that, in the opinion of the

investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include chronic conditions recognized as risk factors for influenza complications or as contraindications for live vaccination, including chronic cardiac (exclusive of hypertension) or pulmonary conditions (including asthma), diabetes mellitus, or renal impairment.

- The subject has an acute illness or an oral temperature greater than 99. 9 degreesF

(37. 7 degrees C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolve > 3 days prior to enrollment.

- The subject is currently participating or plans to participate in a study that

involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period.

- The subject has any condition that would, in the opinion of the site investigator,

place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

- The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C

infection.

- The subject has a previous history of Guillain-Barré syndrome within 6 weeks of

receipt of influenza vaccination.

- The subject has any condition that the principal investigator (PI) believes may

interfere with successful completion of the study.

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States

Vaccine Research Unit Room 3-5000, Rochester, New York 14642, United States

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Starting date: October 2010
Last updated: August 2, 2011