Children aged younger than 3 years receive the same protective antibody
response from the recommended two doses of seasonal influenza vaccines,
regardless of whether the doses were from the live-attenuated influenza vaccine
or the trivalent inactivated vaccine, according to research published online.
Daniel F. Hoft, MD, PhD, of the division of infectious diseases,
allergy and immunology, Saint Louis University School of Medicine, Vaccine
Treatment and Evaluation Unit, and colleagues looked at data from 53 children
aged 6 to 35 months during the 2005-2006 and 2006-2007 influenza seasons.
During the study, all children received an initial dose of licensed
seasonal influenza vaccine and a booster dose 1 month later. In two
groups, the vaccines matched, with children receiving two injections of a TIV
injection or two nasal spray LAIVs (FluMist, MedImmune). Children in the other
two groups received a combination of vaccines, with a dose of LAIV given either
before or after TIV.
The researchers found that all four dosing patterns were safe and
induced similar levels of protective antibodies. However, when the
investigators looked at responses from the T-cell arm of the immune system,
they could not detect influenza-specific T cells in children who received only
TIV.
“Only LAIV induced CD4, CD8, and T cells relevant for broadly
protective heterosubtypic immunity,” the researchers said.
Children who received only one dose of LAIV had T-cell responses similar
to those who received two, and the order of vaccine types did not make a
significant difference in the size of the T-cell response. However, because
LAIV has sometimes been associated with increased incidence of wheezing in the
youngest recipients, the results of this trial suggest that the best regimen
for children aged younger than 24 months may be
TIV followed by LAIV, Hoft said. Larger clinical
trials are required to confirm the safety and efficacy of such an approach, he
added.
Infectious Diseases in Children Editorial Board members
Kathryn M. Edwards, MD, and C. Buddy Creech, MD, MPH, were
co-investigators of the study.
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Eugene Shapiro
|
It is recommended that young children (beginning as early as 6 months of
age) receive two doses of influenza vaccine the first time they are immunized
against influenza. Although studies indicate that trivalent live-attenuated
(cold-adapted) influenza vaccine (LAIV) is more effective in preventing
influenza in children than is trivalent inactived influenza vaccine (TIV), LAIV
cannot be given to children aged younger than 24 months because of the risk of
inducing an attack of asthma. The investigators undertook a small pilot study
to assess the safety and effects of two doses of each possible sequence of
these two vaccines administered a month apart. Conceivably, if a dose LAIV
administered after an initial dose of TIV was safe and not associated with
increased risk of adverse effects, young children might be able to receive the
additional benefit of LAIV. Of course, definitive demonstration of this would
require a large clinical trial.
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Joseph A.
Bocchini
|
The investigators assessed safety as well as immunogenicity and
induction of influenza-specific T-cell memory by different combinations of
these two vaccines in a small number (n=56) of healthy children aged 6-35
months. They found all combinations of these vaccines to be safe and
immunogenic for development of humoral immunity (specific hemagglutination
inhibition antibodies against the influenza viruses contained in the vaccine).
However, only children who received LAIV developed T-cell memory against highly
conserved epitopes of influenza virus that could conceivably provide
heterotypic immunity against types of influenza virus not contained in the
trivalent vaccines. This occurred regardless of whether the child received LAIV
as the first, second or both does. In addition, the investigators found that
T-cells from children who had received LAIV were much more likely than were
T-cells from children who had received only TIV to inhibit replication of
influenza virus in cell culture (including heterotypic viruses not specifically
included in the vaccine). Moreover, children who received LAIV for their first
dose (vaccine virus was recovered from 61% of these children) were
significantly less likely to shed the vaccine virus after a second dose of LAIV
(8%).
However, although shedding of the vaccine virus was lower (30%) in
children who received LAIV as a second dose if they had been previously primed
with TIV compared with children who received LAIV as a first dose (61%), this
difference was not statistically significant. However, because of the small
number of children in each group, the statistical power to demonstrate a
significant difference was poor.
This study is important because it demonstrates a possible explanation
for the greater protection afforded by LAIV. It induces cell-mediated immunity
with T-cell memory, immunity that could also provide some protection against
strains of influenza not included in the vaccine. All of the combinations of
the vaccines were safe in this small pilot study, but a much larger study is
needed to confirm the safety of this approach. While the in vitro data
demonstrate possible reasons to encourage wider use of LAIV, even if the
numbers were large enough that decrease in viral shedding after administration
of LAIV among children who had received their initial dose of vaccine as TIV
was statistically significant, a substantial number (nearly one-third) of these
children still shed the virus. Larger studies are needed to confirm the safety
and effectiveness of this approach, but this is an encouraging start.
Joseph A. Bocchini, MD
Eugene Shapiro,
MD
Infectious Diseases in Children Editorial Board members
Disclosures: Drs. Bocchini and Shapiro report no relevant
financial disclosures.