Influenza Vaccine in Premature Infants

September 15, 2015 updated by: Carl D'Angio, University of Rochester

Influenza Vaccine Immunogenicity in Extremely Premature Infants

Background. Influenza is increasingly recognized as causing severe respiratory illness in children. High-risk infants, like former premature infants, and particularly those with lung disease, have influenza hospitalization rates about five times higher than healthy children. Influenza vaccine does not protect young children against influenza as well as it does healthy adults. A small study that measured antibodies (proteins that protect against infection) to influenza suggested that premature infants get even less protection from influenza vaccine than full-term infants. More information about influenza vaccine in premature infants is needed. The overall goals of this project are to collect information about the how well the influenza vaccine induces antibody production, and to develop the collaborative network of centers necessary for a larger trial of influenza vaccine in premature infants.

Objective and Hypotheses. The objective of this study is to measure the amount of protective antibody produced by influenza vaccine in premature (less than 30 weeks' [about 7 months] gestation at birth), extremely-low-birth-weight (1000 grams [2¼ pounds] or less at birth) infants. Influenza vaccine needs to be given yearly. We will assess premature infants during their first series of influenza vaccines. We hypothesize that the levels of antibody will be lower in premature infants receiving their first series of influenza vaccine than in full-term infants.

Design. We will measure the immune response in premature and full term infants. During the 2007-2008 influenza season, a total of 92 subjects, divided among 2 groups (premature infants 6-17 months old receiving their first influenza vaccine series and full-term infants 6-17 months old receiving their first influenza vaccine series) will be recruited at a consortium of five centers (the University of Rochester, the University of Texas Southwestern Medical Center, Wake Forest University, the University of Miami and the State University of New York at Buffalo), receive 2 doses of influenza vaccine, and have antibody and immune cell responses to each vaccine component measured 4-6 weeks after the second dose of vaccine.

Potential Impact. If this study and future investigations suggested ways to improve premature infants influenza vaccine responses, they could lead to changes in recommendations for the number or timing of vaccine doses or of the type of vaccine used in this high-risk group.

Study Overview

Status

Completed

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. Further investigation is required to optimize vaccine responses in premature infants. The overall goals of this project are to generate estimates of effect size and variance of influenza vaccine immunogenicity for use in planning a larger multi-center trial, and to develop the collaborative network of centers necessary for such a trial.

Objective and Hypotheses. The primary objective of this study is to measure influenza vaccine immunogenicity in extremely-low-birth-weight (ELBW, < 1001 grams at birth), premature (< 30 weeks' gestation) infants receiving trivalent, inactivated, split-virion influenza vaccine (TIV). We hypothesize that the geometric mean titer (GMT) of antibody to each of the three vaccine components will be lower in ELBW infants receiving their first series of TIV than in full-term (FT, >37 weeks' gestation), normal-birth-weight (>2500 grams) infants.

Specific Aim. To measure the humoral and cellular immunogenicity of influenza vaccine in extremely-low-birth-weight (ELBW, greater than or equal to 1000 grams at birth), premature infants receiving trivalent, inactivated, split-virion influenza vaccine (TIV) for their first influenza vaccine series in 2007-8.

Design. This prospective, cohort, immunogenicity study will estimate the GMT to influenza in ELBW infants, with a comparison group of FT infants. Using the established vaccine study infrastructure at a consortium of five centers (the University of Rochester, the University of Texas Southwestern Medical Center, Wake Forest University, the University of Miami and the State University of New York at Buffalo), we will recruit 46 un-immunized (for influenza) ELBW infants, 6-17 months old and 46 un-immunized FT infants, 6-17 months old. Infants will receive the recommended 2 doses of TIV, 4 weeks apart, with blood drawing at the first vaccine dose and 4-6 weeks after the second. Antibody to each vaccine component will be measured by hemagglutination inhibition. The frequency of hemagglutinin-specific T cell interleukin (IL)-2, IL-4 and interferon gamma (IFNγ) responses will be measured by ELISPOT assay. The primary outcome will be influenza GMT. A sample size of 46 subjects per group provides 80% power, using a two-sided alpha = 0.05, to detect a 1.5-fold difference in GMT between groups, assuming a standard deviation (SD) spanning 0.5 to 2.0 times the value of each GMT. In addition, the five-center consortium will monitor the quality of the collaboration, strengthen its capabilities through the design and implementation of a secure, web-based information system, and expand its efforts by seeking additional, outside funding to implement a companion protocol assessing live attenuated influenza vaccine in premature infants.

Potential Impact. This study is designed to assess the immunogenicity of the current generation of influenza vaccines in premature infants. This and future trials assessing novel immunization strategies (such as an additional vaccine dose) or vaccines (for instance, the live attenuated influenza virus vaccine) in premature infants could eventually lead to the tailoring of specific vaccine strategies for this high-risk group. In addition, this proposal would bring to maturity a multi-center, collaborative mechanism for vaccine trials in premature infants.

Study Type

Observational

Enrollment (Actual)

66

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33101
        • University of Miami
    • New York
      • Buffalo, New York, United States, 14222
        • State University of New York at Buffalo
      • Rochester, New York, United States, 14534
        • University of Rochester
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center

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

6 months to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Premature infants < 30 week's gestation, < 1001 grams' birth weight or full-term infants 37-42 week's gestation >2500 grams' birth weight

Description

Inclusion criteria. Subjects must meet all relevant criteria to participate.

  1. (a) Former premature (< 30 weeks' gestation at birth), ELBW (<1001 grams' birth weight) infant, 6 months, 0 days - 17 months, 31 days of age., OR (b) Former full term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 6 months, 0 days - 17 months, 31 days of age.
  2. No prior influenza immunization.
  3. Eligible for influenza immunization.
  4. Parental permission.
  5. Agreement of primary care provider.
  6. 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.
  2. Systemic corticosteroid administration at time of study enrollment.
  3. Requiring supplemental oxygen.
  4. Contraindication to influenza immunization (e.g. egg allergy).
  5. Physician-diagnosed influenza illness in the current influenza season.
  6. 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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
Premature infants
Biological: Trivalent Inactivated Influenza Vaccine
Influenza vaccine
2
Full term infants
Biological: Trivalent Inactivated Influenza Vaccine
Influenza vaccine

Collaborators and Investigators

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

Sponsor

University of Rochester

Collaborators

University of Miami
Wake Forest University Health Sciences
University of Texas Southwestern Medical Center
State University of New York at Buffalo
Thrasher Research Fund

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

October 1, 2007

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

March 30, 2007

First Submitted That Met QC Criteria

March 30, 2007

First Posted (Estimate)

April 3, 2007

Study Record Updates

Last Update Posted (Estimate)

September 17, 2015

Last Update Submitted That Met QC Criteria

September 15, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • URRSRB15397A

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 Trivalent Inactivated Influenza Vaccine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Nigeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe