A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus.

Cytomegalovirus (CMV) is a leading cause of infant hearing loss and neurodevelopmental delay, but there are no clinically licensed vaccines to prevent infection, in part due to challenges eliciting neutralizing antibodies. One of the most well-studied targets for CMV vaccines is the viral fusogen glycoprotein B (gB), which is required for viral entry into host cells. Within gB, antigenic domain 2 site 1 (AD-2S1) is a target of potently neutralizing antibodies, but gB-based candidate vaccines have yet to elicit robust responses against this region. We mapped the genealogy of B cells encoding potently neutralizing anti-gB AD-2S1 antibodies from their inferred unmutated common ancestor (UCA) and characterized the binding and function of early lineage ancestors. Surprisingly, we found that a single amino acid heavy chain mutation A33N, which was an improbable mutation rarely generated by somatic hypermutation machinery, conferred broad CMV neutralization to the non-neutralizing UCA antibody. Structural studies revealed that this mutation mediated key contacts with the gB AD-2S1 epitope. Collectively, these results provide insight into potently neutralizing gB-directed antibody evolution in a single donor and lay a foundation for using this B cell-lineage directed approach for the design of next-generation CMV vaccines.

Is There Still a Role for Peritoneal Drains in Neonatal Pneumoperitoneum? A Single-Center Experience.

INTRODUCTION: Although pneumoperitoneum from necrotizing enterocolitis or spontaneous intestinal perforation is a surgical emergency, risk stratification to determine which neonates benefit from initial peritoneal drainage (PD) is lacking. METHODS: Using a single-center retrospective review of very low birth weight neonates under 1500 g who underwent PD for pneumoperitoneum (January 2015 to December 2023) from necrotizing enterocolitis or spontaneous intestinal perforation, two cohorts were created: drain "responders" (patients managed definitively with PD; includes placement of a second drain) and "nonresponders" (patients who underwent subsequent laparotomy or died after PD). Antenatal/postnatal characteristics, periprocedural clinical data, and hospital outcomes were compared between responders and nonresponders using Student's t-test, chi-squared test, or Kruskal-Wallis test as appropriate, with P < 0.05 considered significant. RESULTS: Fifty-six neonates were included: 31 (55%) drain responders and 25 (45%) nonresponders. Birth weight, gestational age, sex, ethnicity, use of postnatal steroids, and enteral feeds were similar between the cohorts. Nonresponders had higher base deficits (-3.4 versus -5.0, P = 0.032) and FiO2 (0.25 versus 0.52, P = 0.001) after drain placement. Drain responders had significantly shorter lengths of stay (89 versus 148 days, P = 0.014) and lower mortality (6.4% versus 56%, P < 0.001). A subgroup analysis of the nonresponders showed no differences in birth weight, vasopressor requirement, FiO2, or postdrain base deficit between nonresponders who had a drain alone versus laparotomy following drain placement. CONCLUSIONS: PD remains a viable initial therapy for pneumoperitoneum in premature very low birth weight neonates (< 1500 g), demonstrating clinical response in more than half. Ongoing clinical assessment and judgment is imperative after drain placement to ensure continued clinical improvement.