TOPLINE:

Mothers with intrauterine transmission of human cytomegalovirus (CMV) to their newborns despite preconception immunity had higher levels of neutralizing antibodies but had weaker antibody-dependent cell cytotoxicity and fewer long-term memory T cells than mothers of uninfected newborns. These immune features mirrored those of pregnant women with primary CMV infection.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to analyze immunologic features of pregnant women with preconception immunity to human CMV, comparing those who transmitted the virus to their fetus with those who did not.
• Overall, the study enrolled 128 pregnant women (median age, 31-34 years) with preconception immunity:
  • 16 with intrauterine human CMV transmission (congenital CMV group) and 40 without intrauterine transmission (noncongenital group) from the Congenital Human Cytomegalovirus Infection in Lombardy study
  • 72 women with primary infection (26 in the congenital group and 46 in the noncongenital CMV group)
• Blood samples were collected during 13 weeks of gestation and at delivery and evaluated for serum-neutralizing activity against epithelial and fibroblast cell infection, antibody-dependent cell cytotoxicity, and CMV-specific T cells.

TAKEAWAY:

• The congenital CMV group had higher serum-neutralizing antibody titers against epithelial cells (P = .022) and fibroblast cells (P = .0003) than the noncongenital CMV group.
• Antibody-dependent cell cytotoxicity was greater in the noncongenital CMV group than in the congenital CMV group (P = .0004).
• Although the total numbers of interferon gamma-producing CD4+ and CD8+ T cells were similar in the congenital and noncongenital CMV groups, the congenital CMV group had significantly lower percentages of CMV-specific memory T cells (P < .05 for all).
• At 24 months post-infection, memory T-cell profiles in the congenital CMV group resembled those seen after primary infection.

IN PRACTICE:

“Nevertheless, our data indicate that, at least in a European, primarily White population, a fully developed maternal immune response to human CMV, characterised by a high frequency of long-term memory T cells and antibodies capable of inducing ADCC [antibody-dependent cell cytotoxicity], confers protection from viral transmission to the fetus, despite the potential occurrence of nonprimary infection during pregnancy,” the authors wrote.

SOURCE:

This study was led by Paola Zelini, PhD, Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. It was published online on August 18, 2025, in The Lancet Microbe.

LIMITATIONS:

This study was limited by its small sample size and retrospective design. Additional parameters to improve the characterization of protective immunity, including the frequency of cytolytic T cells and other Fc-mediated antibody functions, were not analyzed.

DISCLOSURES:

This study was partially supported by Fondazione Regionale per la Ricerca Biomedica, Ministero della Salute, Ricerca Corrente, and Ricerca Finalizzata. The authors reported having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.