{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T04:17:32Z","timestamp":1793593052767,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pre-term infants in neonatal intensive care units are vulnerable to fungal sepsis. In this patient population, <jats:italic>Candida albicans<\/jats:italic> remains the predominant fungal pathogen causing high morbidity and mortality, despite antifungal therapy. Thus, new preventative\/therapeutic strategies against neonatal candidiasis are needed. Previously, we have reported that vaccination with recombinant forms of the <jats:italic>C. albicans<\/jats:italic> N-termini of the cell wall proteins Als3 (rAls3p-N) and Hyr1 (rHyr1p-N) protected adult mice from disseminated candidiasis. Further, in a Phase 1b\/2a NDV-3A (an rAls3p-N formulated with alum) protected women from recurrent vulvovaginal candidiasis, with anti-Als3p IgG2 isotype being a biomarker for efficacy. Here, we performed a proof of concept study to evaluate if anti-Als3p or anti-Hyr1p antibodies are important for prevention of disseminated candidiasis in neonates. Als3 and Hyr1 antigens when adjuvanted with complete Freund\u2019s adjuvant (CFA)\/incomplete Freund\u2019s adjuvant (IFA) induced a robust antibody response with a ten-fold higher titer of IgG2, than attained by either antigen formulated with alum. Transplacental transfer of these antibodies significantly reduced fungal burden in the kidneys of mice pups, and adoptive transfer of vaccinated mothers\u2019 sera into pups displayed similar levels of protection. Neutrophils were found important for this efficacy. Finally, anti-Hyr1 antisera potentiated the activity of fluconazole in protecting from <jats:italic>C. albicans<\/jats:italic> infection. Our current studies are the first in the field to emphasize the importance of anti-Als3 and anti-Hyr1 antibodies in preventing neonatal candidiasis. Considering that <jats:italic>Candida<\/jats:italic> infections in low birthweight infants is a lethal infection, active and passive vaccination strategies using these antigens could have profound clinical relevance.<\/jats:p>","DOI":"10.3389\/fimmu.2022.925821","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T04:33:05Z","timestamp":1658723585000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Antibodies targeting Candida albicans Als3 and Hyr1 antigens protect neonatal mice from candidiasis"],"prefix":"10.3389","volume":"13","author":[{"given":"Shakti","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunna","family":"Nabeela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Barbarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf S.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Uppuluri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","first-page":"1","article-title":"Births: Final data for 2013","volume":"64","author":"Martin","year":"2015","journal-title":"Natl Vital Stat Rep"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000178291.40568.ef","article-title":"Nosocomial neonatal candidiasis","volume":"24","author":"Bendel","year":"2005","journal-title":"Pediatr Infect Dis J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00013-08","article-title":"Candida parapsilosis, an emerging fungal pathogen","volume":"21","author":"Trofa","year":"2008","journal-title":"Clin Microbiol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-013-9705-5","article-title":"Six-year trend analysis of nosocomial candidemia and risk factors in two intensive care hospitals in mato grosso, Midwest region of Brazil","volume":"176","author":"Hoffmann-Santos","year":"2013","journal-title":"Mycopathologia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2013.814150","article-title":"A prospective study of the patterns and dynamics of colonization with candida spp. in very low birth weight neonates","volume":"45","author":"Leibovitz","year":"2013","journal-title":"Scand J Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.1031108","article-title":"Advances in the treatment of invasive neonatal candidiasis","volume":"16","author":"Botero-Calderon","year":"2015","journal-title":"Expert Opin Pharmacother"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/498318","article-title":"Development and maturation of the immune system in preterm neonates: Results from a whole genome expression study","volume":"2014","author":"Zasada","year":"2014","journal-title":"BioMed Res Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2223\/1301","article-title":"[Immunological peculiarities of extremely preterm infants: A challenge for the prevention of nosocomial sepsis]","volume":"81","author":"Mussi-Pinhata","year":"2005","journal-title":"J Pediatr (Rio J)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1179\/204777312X13462106637684","article-title":"Bridging the gap: Maternal immunisation as a means to reduce neonatal deaths from infectious diseases","volume":"106","author":"Lindsey","year":"2012","journal-title":"Pathog Glob Health"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e3283607a58","article-title":"Maternal immunization as a strategy to decrease susceptibility to infection in newborn infants","volume":"26","author":"Lindsey","year":"2013","journal-title":"Curr Opin Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/j.1469-0691.2012.03936.x","article-title":"Can infants be protected by means of maternal vaccination","author":"Esposito","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.04.068","article-title":"Mother-infant vaccination with pneumococcal polysaccharide vaccine: Persistence of maternal antibodies and responses of infants to vaccination","volume":"29","author":"Holmlund","year":"2011","journal-title":"Vaccine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000361.pub3","article-title":"Intravenous immunoglobulin for preventing infection in preterm and\/or low birth weight infants","volume":"7","author":"Ohlsson","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.602","article-title":"Passive immunity in prevention and treatment of infectious diseases","volume":"13","author":"Keller","year":"2000","journal-title":"Clin Microbiol Rev"},{"key":"B15","article-title":"Use of intravenous immune globulin in newborn infants","author":"Fischer","year":"1994","journal-title":"Clin Exp Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"E2","DOI":"10.1542\/peds.99.2.e2","article-title":"Meta-analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis","volume":"99","author":"Jenson","year":"1997","journal-title":"Pediatrics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/S0146-0005(98)80007-4","article-title":"The role of intravenous immunoglobulin for the prevention and treatment of neonatal sepsis","volume":"22","author":"Jenson","year":"1998","journal-title":"Semin Perinatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy185","article-title":"A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis-a phase 2 randomized, double-blind, placebo-controlled trial","volume":"66","author":"Edwards","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007460","article-title":"The NDV-3A vaccine protects mice from multidrug resistant candida auris infection","volume":"15","author":"Singh","year":"2019","journal-title":"PLoS Pathog"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6194","DOI":"10.1038\/s41598-019-42517-y","article-title":"NDV-3A vaccination prevents c. albicans colonization of jugular vein catheters in mice","volume":"9","author":"Alqarihi","year":"2019","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007056","article-title":"The Hyr1 protein from the fungus candida albicans is a cross kingdom immunotherapeutic target for acinetobacter bacterial infection","volume":"14","author":"Uppuluri","year":"2018","journal-title":"PLoS Pathog"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00076","article-title":"Monoclonal IgM antibodies targeting candida albicans Hyr1 provide cross-kingdom protection against gram-negative bacteria","volume":"11","author":"Youssef","year":"2020","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03722-w","article-title":"Adaptive immunity induces mutualism between commensal eukaryotes","volume":"596","author":"Ost","year":"2021","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025909","article-title":"Active and passive immunization with Rhyr1p-n protects mice against hematogenously disseminated candidiasis","volume":"6","author":"Luo","year":"2011","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1086\/504691","article-title":"Efficacy of the anti-candida Rals3p-n or Rals1p-n vaccines against disseminated and mucosal candidiasis","volume":"194","author":"Spellberg","year":"2006","journal-title":"J Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-006-0121-9","article-title":"The anti-candida vaccine based on the recombinant n-terminal domain of Als1p is broadly active against disseminated candidiasis","volume":"74","author":"Ibrahim","year":"2006","journal-title":"Arch Microbiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1086\/652407","article-title":"Candida albicans Hyr1p confers resistance to neutrophil killing and is a potential vaccine target","volume":"201","author":"Luo","year":"2010","journal-title":"J Infect Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01349","article-title":"Human anti-Als3p antibodies are surrogate markers of NDV-3a vaccine efficacy against recurrent vulvovaginal candidiasis","volume":"9","author":"Uppuluri","year":"2018","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.07.012","article-title":"Neonatal candidiasis: Diagnosis, prevention, and treatment","author":"Greenberg","year":"2014","journal-title":"J Infect"},{"key":"B30","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1542\/peds.2004-2292","article-title":"Neonatal candidiasis among extremely low birth weight infants: Risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months","volume":"117","author":"Benjamin","year":"2006","journal-title":"Pediatrics"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.19.2357","article-title":"Neurodevelopmental and growth impairment among extremely low-Birth-Weight infants with neonatal infection","volume":"292","author":"Stoll","year":"2004","journal-title":"JAMA"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.09.016","article-title":"NDV-3 protects mice from vulvovaginal candidiasis through T- and b-cell immune response","volume":"31","author":"Ibrahim","year":"2013","journal-title":"Vaccine"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nri1394","article-title":"Neonatal adaptive immunity comes of age","volume":"4","author":"Adkins","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1996.tb00172.x","article-title":"Evolution of maternofetal transport of immunoglobulins during human pregnancy","volume":"36","author":"Malek","year":"1996","journal-title":"Am J Reprod Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/985646","article-title":"IgG placental transfer in healthy and pathological pregnancies","volume":"2012","author":"Palmeira","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01120-19","article-title":"Efficacy of delayed therapy with fosmanogepix (APX001) in a murine model of candida auris invasive candidiasis","volume":"63","author":"Wiederhold","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1086\/430952","article-title":"Mice with disseminated candidiasis die of progressive sepsis","volume":"192","author":"Spellberg","year":"2005","journal-title":"J Infect Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky153","article-title":"Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated candida auris infection using an immunocompromised mouse model","volume":"73","author":"Hager","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.671068","article-title":"Vaccine-induced immunological memory in invasive fungal infections - a dream so close yet so far","volume":"12","author":"Biswas","year":"2021","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00897","article-title":"The elusive anti-candida vaccine: Lessons from the past and opportunities for the future","volume":"9","author":"Tso","year":"2018","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1016\/j.celrep.2019.07.047","article-title":"Maternal antibodies inhibit neonatal and infant responses to vaccination by shaping the early-life b cell repertoire within germinal centers","volume":"28","author":"Vono","year":"2019","journal-title":"Cell Rep"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2016.08.025","article-title":"A neonatal mouse model for the evaluation of antibodies and vaccines against coxsackievirus A6","volume":"134","author":"Yang","year":"2016","journal-title":"Antiviral Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1114195","article-title":"Induction of mucosal immunity through systemic immunization: Phantom or reality","volume":"12","author":"Su","year":"2016","journal-title":"Hum Vaccines Immunother"},{"key":"B44","doi-asserted-by":"publisher","first-page":"Cd001239","DOI":"10.1002\/14651858.CD001239.pub6","article-title":"Intravenous immunoglobulin for suspected or proven infection in neonates","volume":"1","author":"Ohlsson","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2011-0257","article-title":"Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: A retrospective analysis","volume":"40","author":"Buxmann","year":"2012","journal-title":"J Perinat Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2013","article-title":"Regression of fetal cerebral abnormalities by primary cytomegalovirus infection following hyperimmunoglobulin therapy","volume":"28","author":"Nigro","year":"2008","journal-title":"Prenat Diagn"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-3782(14)70011-8","article-title":"Role of human cytomegalovirus (HCMV)-specific antibody in HCMV-infected pregnant women","volume":"90","author":"Revello","year":"2014","journal-title":"Early Hum Dev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2012.745503","article-title":"Twin pregnancy and congenital cytomegalovirus: Case report and review","volume":"26","author":"Simioni","year":"2013","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/cid\/cis423","article-title":"Early primary cytomegalovirus infection in pregnancy: Maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age","volume":"55","author":"Visentin","year":"2012","journal-title":"Clin Infect Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00539-18","article-title":"Alexidine dihydrochloride has broad-spectrum activities against diverse fungal pathogens","volume":"3","author":"Mamouei","year":"2018","journal-title":"mSphere"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.925821\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T04:33:09Z","timestamp":1658723589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.925821\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2022.925821"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.925821","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"925821"}}