Study of Live, Attenuated Influenza Vaccination in Preterm and Full-Term Infants

August 4, 2014 updated by: Carl D'Angio, University of Rochester

Immune Responses in Preterm and Full-Term Infants Following Live, Attenuated Influenza Vaccination

Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. The recently-licensed live attenuated influenza vaccine (LAIV) promotes better immune responses than the trivalent inactivated vaccine, but can cause wheezing. The balance of risks and benefits for LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.

The specific aim of this project is to compare the immune response and reactions of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very (V) LBW and former full-term (FT) infants aged 24-35 months.

The investigators hypothesize that the immune response in FT infants will be greater with LAIV than TIV, and that wheezing episodes will be no more than twice as frequent in LAIV as in TIV recipients.

The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Children will be randomized to receive one dose either TIV or LAIV. Vaccine reactions will be measured. One to two teaspoons mL of blood will be drawn at 0 and 7-14 days from immunization, and less than one teaspoon of blood will be drawn at 28-42 days.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Background. Influenza infection causes an estimated 1 million deaths worldwide yearly. Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. Influenza vaccine immunogenicity is generally modest even in healthy children, and influenza vaccines have been incompletely studied in premature infants. The recently-licensed live attenuated influenza vaccine (LAIV) is more immunogenic than the trivalent inactivated vaccine, but its use in infants and high risk children is limited by side effects. The risk/benefit ratio of LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.

Aim. The specific aim of this project is to compare the immunogenicity and reactogenicity of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very low birth weight (VLBW) and former full-term (FT) infants aged 24-35 months.

Hypotheses.

  1. The humoral immunogenicity of LAIV, as measured by hemagglutination inhibition (HI), will be greater than that of TIV. This will be the co-primary outcome for this study.
  2. Vaccine reactogenicity, as measured by medically-attended wheezing episodes, will be no more than twice as frequent in LAIV as in TIV recipients. This will be the co-primary outcome for this study.
  3. Functional B-cell responses, as measured by antibody secreting cell (ASC) enzyme linked immunospot (ELISPOT), will be greater in LAIV-immunized infants than TIV-immunized infants.
  4. Peak T-cell cytokine responses, as measured by interferon gamma (IFNγ), interleukin (IL)-2 and IL-4 ELISPOT, will be greater in LAIV-immunized infants than TIV-immunized infants.
  5. Hemagglutinin-specific nasal immunoglobulin A (IgA) will be measureable following LAIV immunization.
  6. Former premature infants will have similar adaptive immune responses, but elevated reactogenicity to both vaccines, when compared to former full-term infants.

Design. The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Subjects, who will be eligible to receive either TIV or LAIV as part of routine care, will be randomized to receive one dose either TIV or LAIV, according to prevailing recommendations for influenza immunization. Randomization will be stratified by prematurity status. Vaccine reactogenicity will be measured by using parent diaries following immunization and questionnaires at each visit. Five to 10 mL of blood will be drawn at 0 and 7-14 days from immunization for isolation of peripheral blood mononuclear cells (PBMC), and 1 mL of blood will be drawn for serum separation for antibody determination at 0 and 28-42 days. Antibody levels and T- and B-cell responses to vaccine will be measured.

Potential Impact. This study is designed to assess the immunogenicity and reactogenicity of two current influenza vaccines in premature infants. The data will be used to estimate the sample size for a definitive trial in younger premature infants.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 2 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Subjects must meet all relevant criteria (by time of influenza vaccination) to participate.

  1. (a) Former premature (<32 weeks' gestation at birth), VLBW (<1500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age, OR (b) Former full-term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age.
  2. Influenza immunization in prior season.
  3. Eligible for either influenza immunization (TIV or LAIV).
  4. Parental permission.
  5. Parents likely to be able to comply with study visits.

Exclusion Criteria:

Subjects may not participate if they meet any one of these criteria.

  1. Known immunodeficiency in child or in a close household contact.

  2. History of:

    • Recurrent episodes of wheezing,
    • Medically-attended wheezing illness in past year, or
    • Hospitalization for a wheezing illness.
  3. Systemic corticosteroid administration at time of influenza vaccination.
  4. Requiring supplemental oxygen at time of influenza vaccination.
  5. Contraindication to either influenza immunization (e.g. egg allergy, aspirin therapy).
  6. Physician-diagnosed influenza illness in the current influenza season.
  7. Any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the subject.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Live attenuated influenza vaccine
One dose of live attenuated influenza vaccine, according to routine immunization recommendations
Biological: Live attenuated influenza vaccine
One dose of live attenuated influenza vaccine, according to routine immunization recommendations
Other Names:
  • FluMist
Active Comparator: Inactivated influenza vaccine
One dose of inactivated influenza vaccine, according to routine immunization recommendations
Biological: Inactivated influenza vaccine
One dose of inactivated influenza vaccine, according to routine immunization recommendations
Other Names:
  • Fluzone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Humoral Immunogenicity
Time Frame: 28-42 days
Hemagglutinin specific antibody, as measured by hemagglutination inhibition
28-42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medically-attended Wheezing
Time Frame: 42 days
Wheezing that triggers a visit for medical care
42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Investigators

  • Principal Investigator: Carl T. D'Angio, MD, University of Rochester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

August 31, 2010

First Submitted That Met QC Criteria

September 1, 2010

First Posted (Estimate)

September 2, 2010

Study Record Updates

Last Update Posted (Estimate)

August 22, 2014

Last Update Submitted That Met QC Criteria

August 4, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25914

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Influenza

Clinical Trials on Live attenuated influenza vaccine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Vietnam

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe