127. Perinatal Protection Against Invasive Neonatal Candidiasis By a Monoclonal Antibody Targeting the Candida albicans Adhesin, Als3p
Session: Oral Abstract Session: Potpourri of Pediatric Infections
Thursday, October 3, 2013: 11:00 AM
Room: The Moscone Center: 250-262
Background: Neonatal candidiasis is the third most common cause of late-onset neonatal sepsis. Despite treatment with antifungal agents, death or neuro-developmental impairment is observed in 73% of infected infants. Previously, we determined that a monoclonal antibody against the C. albicans surface adhesin, Als3p (anti-Als3p MAb) afforded protection in a mouse model of neonatal candidiasis when used as a therapeutic or prophylactic agent.  Here, we determined the kinetics of perinatal transfer of anti-Als3p MAb following administration to pregnant dams and the protection offered against invasive neonatal candidiasis in their pups.

Methods: Anti-Als3p MAb was administered by intravenous injection to pregnant Balb/c mice (E19). Control mice received saline. After birth, pups were given an intra-peritoneal infective challenge with 5 x 106 cfu of C. albicans. Mortality characteristics and fungal burden in the kidney, liver, lung and brain were evaluated at death or at 72 hours in surviving pups. The persistence of MAb in circulation was evaluated by immunofluorescence microscopy in timed sera following injection in dams and at terminal bleed of control (unchallenged) neonatal mice born to these dams.

Results:  Mortality in infected pups born to mothers immunized with anti-Als3p MAb was lower than those born to saline control mothers (33% vs. 50%). Median fungal colony counts in the liver (90000 vs. 378000, p<0.05) and kidney (830 vs. 5160, p<0.05) were significantly lower in treated mice compared to saline control mice. The presence of anti-Als3p MAb was confirmed by immunofluorescence microscopy in the sera of adult mice up to 25 days post-injection and in unchallenged neonatal mice, whose mothers had been injected in pregnancy, at the time of terminal bleed on day 7 after birth.

Conclusion: Anti-Als3 MAb is transferred perinatally from dams to pups, protects against invasive C. albicans infection and could potentially be utilized as a preventive strategy in neonatal candidiasis. Additionally, this study provides proof-in-principle evidence for the capability of monoclonal antibodies to provide humoral immunity against etiological agents of neonatal sepsis following antenatal administration.

Anoop Pulickal, MD, PhD, Neonatology, Brown University/ Women & Infants Hospital, Providence, RI, Sonia Laforce-Nesbitt, MS, Neonatology, Women and Infant's Hospital, Providence, RI, Lois Hoyer, PhD, Pathobiology; Institute of Genomic Biology, University of Illinois At Urbana-Champaign, Urbana, IL and Joseph Bliss, MD, PhD, Pediatrics, Women and Infants Hospital, Providence, RI

Disclosures:

A. Pulickal, None

S. Laforce-Nesbitt, None

L. Hoyer, None

J. Bliss, None

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