An unusual antibody shows super activity against Zika virus

A team led by researchers at Weill Cornell Medical College, New York-Presbyterian Church, and the National Institutes of Health (NIH) has discovered an unusual antibody that neutralizes the Zika virus even at extremely low levels and makes the viral infection undetectable
in preclinical models.
Because Zika virus can cause birth defects when transmitted from a pregnant woman to a fetus, this finding could lead to the development of treatments to protect babies from the potentially devastating effects
of the disease.

In a study published Nov.
18 in the journal Cell, researchers used blood cells taken from pregnant women infected with Zika virus to isolate a super-potent immunoglobulin M (IgM) antibody — a five-arm immune protein that can attach to
the virus.
In mouse experiments, they determined that the antibody not only protected the animals from other deadly infections, but also suppressed the virus, making it undetectable
in the blood.

Zika virus is currently circulating at low levels in many tropical countries, but this will inevitably change, said co-senior author Dr Sallie Permar
.
Mattia Bonsignori, Ph.
D.
, head of the Division of Translational Immunobiology in the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, is a co-senior author
of the study.

"It is important that we prepare for another outbreak of Zika," Permar said
.

At this point, doctors do not have approved vaccines or treatment regimens to offer to patients
.
Dr.
Permar said that with further research, this antibody may help fill this gap
.
"There are two possible ways to use it: to rapidly reduce the level of Zika virus in the blood of infected pregnant women, and to provide it as a preventive measure during an outbreak to those at risk of infection
.
"

Zika virus is transmitted by infected Aedes aegypti mosquitoes and usually causes mild illness
in adults.
However, Zika virus infection in pregnant women can cause serious birth defects, including unusually small heads and brain damage
in babies.

During the Zika virus outbreak that began in 2015, researchers in Brazil, led by Dr.
Reynaldo Dietze of Global Health and Tropical Medicine and Dr.
Camila Giuberti of the Federal University of Sacred Tree Festival, collected blood samples
from infected pregnant women.
The team decided to focus on people who were infected with Zika but gave birth to babies who appeared healthy because they suspected the patients might contain antibodies
that would prevent this congenital infection.

One of the patients gave birth to a apparently healthy baby
nearly two months after Zika virus was detected in the blood (an unusually long time).
The lab team, led by first author Tulika Singh, found that their B cells produced an IgM antibody with a powerful ability to stop viral particles from invading the cells
.

This antibody is called DH1017
.
The emergence of IgM surprised researchers because it belongs to a generally weaker, less mature type of antibody that is produced
early in infection.
However, in this case, the power of this antibody relies on the fact that it is an IgM antibody
.
When the collaborators examined its molecular structure as it bound to the virus, they found that multiple arms could grab a virion
at the same time.
The authors say the findings suggest that IgM antibodies may be particularly effective
against Zika and possibly other viruses.

To develop this antibody as a therapy, the researchers plan to begin testing its safety and how effective it is in preventing transmission to the fetus
in additional preclinical models.
Recalling the exclusion of pregnant women from COVID-19 vaccine trials, Dr.
Pemar stressed that pregnant women
must be included in human studies of new prevention or treatment methods for Zika virus.
"Pregnant women are the ones who need the Zika vaccine or immunotherapy," she said
.
"It is critical
that anti-Zika vaccines and therapies that are safe during pregnancy are available as soon as evidence of a Zika virus outbreak is available.
"