Influenza Clinical Trial
Official title:
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
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