Abstract
Candida infections are frequent and major causes of septicemia in neonatal intensive care units, and neonatal
candidiasis is associated with high morbidity and mortality rates. Low birth weight preterm infants (LBWI) are
especially vulnerable to these infections, despite advances in current antifungal drug regimen. The high morbidity
related to invasive candidiasis demands consideration of novel strategies for curtailing the incidence of these
infections. We are at the crossroads of harnessing novel immunotherapeutic approaches for treatment of
candidiasis in neonates. Our group has developed the very first vaccines against Candida, based on the cell wall
antigens of C. albicans (Als3, Hyr1, Sap2). Vaccination with any of the three antigens elicits a robust immune
response that protects from disseminated as well as mucosal Candida infections, in pre-clinical animal studies.
Two of these vaccines (rAls3p or NDV-3A and rSap2p) have already been adjudged safe and well tolerated in
humans in Phase I clinical trials, and NDV-3A vaccination has proven efficacious in protecting women against
recurrent vulvovaginal candidiasis in Phase 1B/2A trials. Further, passive immunization using antibodies raised
against the antigens Hyr1 and Sap2, protect mice from hematogenously disseminated candidiasis, by
neutralizing antigens’ virulence functions and inhibiting inflammatory responses. We now propose to use these
vaccines to cover the spectrum of Candida infections in pre-term infants. We will use both active maternal
vaccination as well as passive antibody transfusion in pregnant mice, with the ultimate goal to obtain potentially
protective, vertically transferred antibodies in neonates. In addition, the potency of anti-Candida antibodies to
protect from disseminated candidiasis, will also be evaluated after passive transfer in new born mice. Our
overreaching goal is to develop a robust immunization-based approach that can potentially be used
independently, or augment antifungal prophylaxis for ultimately defending low-birthweight infants from
candidiasis. The outcomes of this proposal will be a first foray in the direction of understanding the immune
response against Candida infections during pregnancy, and in neonates. The lessons learnt from our studies will
result in reducing morbidity, mortality and healthcare costs, associated with these difficult to treat infections.