“These findings certainly have implications for the types of immune responses HCMV vaccines should be targeting,” said senior author Dr. Sallie Permar, the Nancy C. Paduano Professor in Pediatrics and Chair of Pediatrics at Weill Cornell Medicine and Pediatrician-in-Chief at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children’s Hospital. The first author of the study is Dr. Eleanor C. Semmes, a physician scientist doctoral candidate in the Department of Molecular Genetics and Microbiology at Duke University School of Medicine.
HCMV and related viruses in the Herpesvirus family are believed to have been infecting humans and other mammals for at least tens of millions of years. During that time, these viruses have developed myriad tools and strategies to evade their hosts’ immune defenses and establish long-term infections. HCMV is thought to infect most individuals in developed countries and virtually all people in developing countries. While most infections go unnoticed, HCMV as it smolders in the bodyfor life, usuallyis thought to subtly promote multiple human ailments, from cancers to heart disease. Moreover, a weak immune system from HIV, immunosuppressive drugs, or being very old or young, can trigger HCMV spread and potentially fatal illness.
Cytomegalovirus and your Baby
HCMV sustains itself in the human population in part by mother-to-child transmission during pregnancy. These congenital HCMV infections can cause stillbirth, hearing loss, brain development abnormalities and other conditions in young children; and preventing them is a major public health goal. But conventional vaccine and antibody-based therapy strategies have so far proven ineffective against congenital HCMV infectionunderscoring the need to understand how the immune system can fight this virus effectively.
“Currently when a mom does have acute CMV infection, or is known to have an infected fetus, we have nothing to offer in terms of vaccines or immunotherapies,” Dr. Permar said.
For the study, she and her team made use of banked maternal and infant umbilical cord blood samples in the Carolinas Blood Bank at Duke University School of Medicinewhere Dr. Permar was based at the study outset. Forty-one of the HCMV-infected mothers had transmitted the virus to their newborns; the other 40 hadn’t.
One remarkable finding concerned ‘neutralizing antibodies.’ These are antibodies that bind to vulnerable sites on the virus and thereby directly disruptneutralizethe virus’s ability to infect cells, reproduce and spread in standard lab dish tests. Normally, vaccines against a virus aim to elicit neutralizing antibodies; prior, unsuccessful HCMV vaccines have done this too. But Dr. Permar and colleagues found that higher levels of HCMV-neutralizing antibodies in maternal blood were not associated with a lower risk of mother-child transmission.
They did find evidence, though, that mothers who didn’t pass on the virus had higher levels of antibody-dependent cellular phagocytosis. That suggests that this indirect mode of antibody immunity, in which antibody proteins use their ‘tail’ sections, called Fc regions, to summon virus-gobbling macrophages and other white blood cells, is one that HCMV is not as adept at escaping.
The results will certainly guide HCMV vaccine efforts with new-found speed in wake of the SARS-CoV-2 vaccine success. Dr. Permar and colleagues are currently applying these findings in work with the vaccine company Moderna, which is developing a candidate HCMV vaccine using the versatile mRNA platform.
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