肥胖者流感疫苗注射後一年，血清中抗體量比體重正常者降低得快，可以說明肥胖者為何比較常受到流感病毒感染。
Obesity Yields Less Protection From
Influenza Vaccine CME/CE
News Author: Larry Hand
CME Author: Penny Murata, MD
Clinical Context
According to the Centers for Disease Control and Prevention
in the July 17, 2009, issue of MMWR. Morbidity and Mortality Weekly Report,
obesity was identified as an independent risk factor for influenza morbidity
and mortality during the influenza A/H1N1/2009 pandemic. In the March 10, 2010,
issue of the Journal of Immunology, Karlsson and colleagues reported impaired
CD8+ T-cell memory response to secondary influenza challenge in obese mice.
However, the immune response in obese humans is not clear.
This ongoing, prospective observational study by Sheridan
and colleagues assesses the effect of body mass index (BMI) on humoral and
cell-mediated immune responses to influenza vaccination.
Study Synopsis and Perspective
As the influenza season opens this month, researchers at the
University of North Carolina at Chapel Hill warn for the first time that
obese individuals may be getting less protection from vaccines than
healthy-weight people. They reported their conclusions in an article published
online October 25 in the International Journal of Obesity.
In an ongoing study involving patients getting vaccinated at
an academic outpatient center, results from the first 2 years indicate that higher
BMI is associated with a larger drop in influenza antibodies 12 months after
vaccination with trivalent influenza vaccine. Previous research had linked
obesity to risk for influenza infection, but this is the first time
researchers have tested for antibodies a year after vaccination.
Using serum tests just after vaccination, Patricia
Sheridan, PhD, from the Department of Nutrition, Gillings School of Global
Public Health, University of North Carolina at Chapel Hill, and colleagues
found that weight did not make a significant difference in the initial response to trivalent influenza vaccine. However,
in testing for CD8+ T-cell responses to vaccines 12 months later, the
researchers discovered that as obesity levels increased, influenza antibodies
decreased up to 4-fold. The CD8+ T-cells do not prevent infection by
influenza, but they do help decrease severity and speed up viral clearance.
"These results suggest that overweight and obese people
would be more likely than healthy weight people to experience flu illness
following exposure to the flu virus," Melinda Beck, PhD, professor and
associate chair of nutrition at the University of North Carolina Gillings
School of Global Public Health and senior author, said in a statement.
"These new findings seem to give us a reason why obese people were more
susceptible to influenza illness during the H1N1 pandemic compared to healthy
weight people."
Researchers tested 461 adult patients aged 18 years or older
during the 2009 influenza season, as well as 74 patients for the 2010 season.
Of all the participants, 29.7% were healthy-weight individuals (BMI, 18.5 -
24.9 kg/m2), 33.4% were overweight (BMI, 25 - 29.9 kg/m2),
and 35.5% were obese (BMI, ≥30 kg/m2). The remaining 1.4% were
underweight.
Twelve months after vaccination, 50% of the obese patients
showed at least a 4-fold decrease in antibody titers to 2 influenza strains. In comparison, less than 25% of the healthy-weight
patients experienced similar large decreases in antibody titers.
Obesity also has been shown to reduce antibody response to
hepatitis B vaccine in adults, and tetanus vaccine in children.
According to the World Health Organization, more than 10% of
the world population is obese, and more than two thirds of the US population is
overweight or obese.
Int J Obes.
Published online October 25, 2011. Full text
Study Highlights
- 499 adults at least 18 years
old were enrolled at an outpatient primary care facility. - All were scheduled to receive
the 2009-2010 seasonal trivalent influenza vaccine. - Exclusion criteria were
immunosuppression, immunomodulator or immunosuppressive drug use, acute
febrile illness, hypersensitivity to any influenza vaccine components,
history of Guillain-Barré syndrome, and theophylline or warfarin use. - Baseline evaluation included
height, weight, and serum sample. - All patients received a single
dose of 2009-2010 seasonal trivalent influenza vaccine containing
A/Brisbane/59/2007 (H1N1), A/Brisbane/10/2007 (H3N2), and
B/Brisbane/60/2008 in the deltoid muscle. - 29.7% of patients were healthy
weight, 1.3% were underweight, 33.4% were overweight, and 35.5% were
obese. - Average age ranged from 45.6 to
59.7 years. - 65.2% were women, 67.0% were
white, and 27.1% were African American. - Primary outcome measures were
antibody response to the trivalent influenza vaccine at 1 and 12 months
after vaccination. - 461 participants (92%)
underwent postvaccination blood draw at 1 month (28 - 35 days), and 61
underwent postvaccination blood draw at 12 months. - Immunoglobulin G antibodies to
the 2009-2010 seasonal trivalent influenza vaccine antigen were quantified
by the enzyme-linked immunosorbent assay. - At 1 month after vaccination,
BMI correlated positively with an increase in antibody fold response. - At 1 month, higher antibody
responses occurred in younger participants, African Americans vs white
participants, and women vs men. - At 1 month, a subset of 38
pairs matched for age, race, and sex showed that obese vs healthy-weight
participants had a higher-fold increase in hemagglutination inhibition
antibodies for the B/Brisbane/60/2008 strain, but there were no
differences for the other 2 strains. - At 12 months after vaccination,
BMI correlated negatively with antibody titers. - At 12 months, a subset of 17
matched pairs showed that obese vs healthy-weight participants had a
greater decrease in hemagglutination inhibition titers. - At 12 months after vaccination,
peripheral blood mononuclear cells were challenged ex vivo with the live
vaccine strain influenza A/Brisbane/59/2007 (H1N1) and were analyzed for
CD3, CD8, CD69, interferon-ɣ, and granzyme B expression: - CD8+ T-cell expression of the
early-activation marker CD69 was reduced in obese vs healthy-weight
participants. - CD8+ T-cell expression of
interferon-ɣ was reduced in obese vs healthy-weight participants and in
overweight vs healthy-weight persons. - CD8+ T-cell expression of
granzyme B was reduced in obese vs healthy-weight persons but was not
significantly different in overweight vs healthy-weight persons. - CD8+ T-cell total numbers were
similar for obese vs healthy-weight participants.
Clinical Implications
- Increasing BMI is linked with
an increased antibody response to the trivalent influenza vaccine at 1
month after vaccination but decreases antibody response at 12 months after
vaccination. - Activation of CD8+ T cells and
expression of interferon-ɣ and granzyme B in influenza-stimulated
peripheral blood mononuclear cell cultures are reduced in obese vs
healthy-weight persons. Expression of interferon-ɣ is also reduced in
overweight vs healthy-weight persons.
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