Background:
The four d
engue
virus serotypes
(DENV
1
-
4
)
and Zika
virus
(ZIKV) are related
mosquito
-
borne flaviviruses
of major importance
globally
.
While monoclonal
antibodies
and plasma
from DENV
-
immune donors
can
neutralize
or enhance
ZIKV
in vitro
and in
small
animal
models
,
and
vice versa
,
the extent
,
duration
, and significance
of cross
-
reactivity
remain
s
unknown,
particularly in
flavivirus
-
endemic
regions
.
Methods:
W
e studied
neutralizing
antibodies
to ZIKV and DENV1
-
4
in
longitudinal
serologic
specimens
through
3 years post
-
infection
from
people
in Latin America and Asia
with laboratory
-
confirmed DENV infections
.
We also evaluated neutralizing
antibodies
to ZIKV and
DENV1
-
4 in Zika patients
through
6 months post
-
infection.
Results:
In Zika patients, the highest neutralizing antibody titers were to ZIKV, with
low
-
level cross
-
reactivity to DENV1
-
4 that was greater in DENV
-
immune
individuals.
We found in
primary and
secondary
DENV infections, neutralizing
antibody
titers to ZIKV were
markedly
lower than to the infecting DENV
and
heterologous DENV serotypes.
Cross
-
neutralization was greatest in
early convalescence
,
then
ZIKV neutralization
decreased, remaining
at low levels
over time.
Conclusions:
Patterns of a
ntibody cross
-
neutralizat
ion
suggest
ZIKV
lies
outside the DENV
serocomplex.
Neutralizing antibody titers can distinguish ZIKV from DENV infections when all viruses are analyzed simultaneously.
These findings
have
implications for
understanding
natural immunity and vaccines.