Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(9)
Published: Feb. 26, 2025
Repeated
mRNA
COVID-19
vaccination
increases
spike-specific
immunoglobulin
G4
(IgG4)
titers.
Here,
we
characterized
the
influence
of
increased
IgG4
titers
on
a
range
Fc-mediated
responses.
Elevated
reduced
binding
to
FcγRIIIa
and
decreased
antibody-dependent
cellular
cytotoxicity.
However,
in
individuals
with
lower
total
IgG,
acted
synergy
other
IgG
subclasses
improve
FcγRI
FcγRIIa
consequently
phagocytosis.
Furthermore,
this
trend
was
more
pronounced
recent
SARS-CoV-2
variants
where
induced
comparably
These
observations
were
further
confirmed
by
silico
modeling
antibody
subclass
concentrations
FcγR
polymorphisms
modulated.
Collectively,
illustrate
that
impact
elevated
upon
Fc
functions
is
dependent
multiple
interconnected
antigen
factors,
which
should
be
taken
into
consideration
when
dissecting
mechanisms
driving
an
effective
response
following
vaccination.
Language: Английский
Immunoglobulin G genetic variation can confound assessment of antibody levels via altered binding to detection reagents
Ruth A Purcell,
No information about this author
L. Carissa Aurelia,
No information about this author
Robyn Esterbauer
No information about this author
et al.
Clinical & Translational Immunology,
Journal Year:
2024,
Volume and Issue:
13(3)
Published: Jan. 1, 2024
Abstract
Objectives
Amino
acid
variations
across
more
than
30
immunoglobulin
(Ig)
allotypes
may
introduce
structural
changes
that
influence
recognition
by
anti‐Ig
detection
reagents,
consequently
confounding
interpretation
of
antibody
responses,
particularly
in
genetically
diverse
cohorts.
Here,
we
assessed
a
panel
commercial
monoclonal
anti‐IgG1
clones
for
capacity
to
universally
recognise
two
dominant
IgG1
haplotypes
(G1m‐1,3
and
G1m1,17).
Methods
Four
anti‐human
were
via
ELISAs
multiplex
bead‐based
assays
their
ability
bind
G1m‐1,3
G1m1,17
variants.
Detection
antibodies
validated
against
allotype
standards
tested
antigen‐specific
plasma
from
homozygous
heterozygous
SARS‐CoV‐2
BNT162b2
vaccinated
(
n
=
28)
COVID‐19
convalescent
44)
individuals.
An
Fc‐specific
pan
‐IgG
corroborated
differences
between
hinge‐
responses.
Results
Hinge‐specific
clone
4E3
preferentially
bound
compared
IgG1.
Consequently,
Spike‐specific
levels
detected
G1m1,17/G1m1,17
vaccinees
appeared
9‐
17‐fold
higher
G1m‐1,3/G1m‐1,3
vaccinees.
equivalently
variants,
comparable
haplotypes.
responses
other
human
coronaviruses
influenza
similarly
poorly
subjects.
Conclusion
Anti‐IgG1
confounds
assessment
clinical
cohorts
owing
bias
towards
Validation
should
include
evaluation
binding
relevant
as
the
role
immunogenetics
upon
humoral
immunity
is
increasingly
explored
populations.
Language: Английский
Intravenous immunoglobulin as a potential treatment for long COVID
Expert Opinion on Biological Therapy,
Journal Year:
2023,
Volume and Issue:
23(12), P. 1211 - 1217
Published: Dec. 2, 2023
Introduction
On
31
July
2023,
the
United
States
Department
of
Health
and
Human
Services
announced
formation
Office
Long
COVID
Research
Practice
National
Institutes
(NIH)
opened
enrollment
for
therapeutic
arm
RECOVER
initiative,
a
prospective,
randomized
study
to
evaluate
new
treatment
options
long
coronavirus
disease
2019
(long
COVID).
Language: Английский
Comparative Efficacy of Parenteral and Mucosal Recombinant Probiotic Vaccines Against SARS-CoV-2 and S. pneumoniae Infections in Animal Models
Vaccines,
Journal Year:
2024,
Volume and Issue:
12(10), P. 1195 - 1195
Published: Oct. 19, 2024
The
accumulation
of
specific
IgG
antibodies
in
blood
serum
is
considered
a
key
criterion
for
the
effectiveness
vaccination.
For
several
vaccine-preventable
infections,
quantitative
indicators
humoral
response
have
been
established,
which,
when
reached,
provide
high
probability
protection
against
infection.
presence
such
formal
correlate
vaccine
crucial,
example,
organizing
preventive
measures
and
validating
newly
developed
vaccines.
However,
can
effective
infection
occur
level
lower
than
that
provided
by
parenteral
vaccination?
Will
be
sufficient
if
same
antigen
administered
via
mucosal
membranes
without
achieving
levels
circulating
blood?
Language: Английский
Antibody glycosylation correlates with disease progression in SIV‐Mycobacterium tuberculosis coinfected cynomolgus macaques
Clinical & Translational Immunology,
Journal Year:
2023,
Volume and Issue:
12(11)
Published: Jan. 1, 2023
Abstract
Objectives
Tuberculosis
(TB)
remains
a
substantial
cause
of
morbidity
and
mortality
among
people
living
with
human
immunodeficiency
virus
(HIV)
worldwide.
However,
the
immunological
mechanisms
associated
enhanced
susceptibility
HIV‐positive
individuals
remain
largely
unknown.
Methods
Here,
we
used
simian
(SIV)/TB‐coinfection
Mauritian
cynomolgus
macaque
(MCM)
model
to
examine
humoral
responses
from
plasma
SIV‐negative
(
n
=
8)
SIV‐positive
7)
MCM
8‐week
postinfection
Mycobacterium
tuberculosis
Mtb
).
Results
Antibody
were
impaired
during
SIV
coinfection.
Elevated
inflammatory
bulk
IgG
antibody
glycosylation
patterns
observed
in
coinfected
macaques
early
at
post‐
infection,
including
increased
agalactosylation
(G0)
reduced
di‐galactosylation
(G2),
which
correlated
endpoint
bacterial
burden
gross
pathology
scores,
as
well
time‐to‐necropsy.
Conclusion
These
studies
suggest
that
immunity
may
contribute
control
TB
disease
support
growing
literature
highlights
Fc
biomarker
progression.
Language: Английский
Identification of IgG1 and IgG3 Allotypes by PCR and Sanger Sequencing
L. Carissa Aurelia,
No information about this author
Ruth A Purcell,
No information about this author
Amy W. Chung
No information about this author
et al.
Methods in molecular biology,
Journal Year:
2024,
Volume and Issue:
unknown, P. 201 - 218
Published: Jan. 1, 2024
Language: Английский
How could our genetics impact COVID-19 vaccine response?
Expert Review of Clinical Immunology,
Journal Year:
2024,
Volume and Issue:
20(9), P. 1027 - 1039
Published: April 27, 2024
Introduction
The
COVID-19
pandemic,
caused
by
the
SARS-CoV-2
virus,
has
posed
unprecedented
global
health
challenges
since
its
emergence
in
December
2019.
rapid
availability
of
vaccines
been
estimated
to
save
millions
lives,
but
there
is
variation
how
individuals
respond
vaccines,
influencing
their
effectiveness
at
an
individual,
and
population
level.
Language: Английский