Influenza Vaccine in Premature Infants
Condition: Influenza; Infant, Premature
MeSH terms: Influenza, Human; Premature Birth
Study type: Observational

Summary: 
      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.
    

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.
    

Intervention name(s): Trivalent Inactivated Influenza Vaccine
Intervention type(s): Biological
Intervention description(s): Influenza vaccine
Observational model: Cohort
Time perspective: Prospective
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
      
Biospecimen description: 
      No retention
    
Keywords: Influenza; Infant, Premature; Immunization; Vaccination