{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:59:57Z","timestamp":1784163597000,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\n                        <jats:italic>Pneumocystis<\/jats:italic>\n                        jirovecii\n                      <\/jats:italic>\n                      causes life-threatening fungal pneumonia (PJP) and other serious pulmonary sequelae in HIV infected individuals and other immunocompromised populations. In recent years, while the frequency of PJP has declined in HIV infected individuals treated with anti-retroviral therapies, the incidence has increased among non-HIV populations due to the expanding use of corticosteroids and other immunomodulatory agents to treat immune-mediated inflammatory diseases and hematologic and solid malignancies. Despite the success of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, patients who are unable to tolerate treatment, take drugs where TMP-SMX is contraindicated, or experience breaks in daily compliance remain at risk. Immunocompromised populations would benefit from vaccine strategies that reduce morbidity and mortality due to acute PJP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Herein, we used a newly established non-human primate (NHP) model of\n                      <jats:italic>Pneumocystis<\/jats:italic>\n                      infection in the context of drug-induced immunosuppression to test the immunogenicity and protective efficacy of a vaccine strategy administered prior to and throughout drug-induced immunosuppression using the \u2018pan-fungal\u2019 vaccine candidate NXT-2a. Longitudinal blood and bronchoalveolar lavage sampling was performed to monitor anti-NXT-2a antibody titers, lymphocyte populations, and infection status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunization with NXT-2a prior to immunosuppression induced robust humoral immune responses in healthy outbred macaques. Subsequent therapeutic boosting throughout drug-induced immunosuppression prevented protective antibody titer decline. Our collective vaccination strategy provided significant protection against\n                      <jats:italic>Pneumocystis<\/jats:italic>\n                      infection throughout the duration of the study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These studies demonstrate the efficacy and feasibility of an NXT-2a based vaccination strategy in a NHP model with a planned immunosuppressive regimen. This strategy may be further applied toward other opportunistic fungal pathogens, such as\n                      <jats:italic>Candida<\/jats:italic>\n                      spp. and\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp. in similarly immunosuppressed populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1729080","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T06:32:28Z","timestamp":1768545148000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective efficacy of a \u2018pan-fungal\u2019 vaccination strategy against experimental Pneumocystis infection in drug-immunosuppressed macaques"],"prefix":"10.3389","volume":"16","author":[{"given":"Whitney","family":"Rabacal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Kirton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor I.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Wychrij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwadwo O.","family":"Oworae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1086\/591701","article-title":"Relationship of Pneumocystis antibody response to severity of chronic obstructive pulmonary disease","volume":"47","author":"Morris","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2020-000842","article-title":"Relationship of Pneumocystis antibody responses to paediatric asthma severity","volume":"8","author":"Rayens","year":"2021","journal-title":"BMJ Open Respir Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jinf.2016.05.001","article-title":"Increased prevalence of Pneumocystis jirovecii colonisation in acute pulmonary exacerbations of cystic fibrosis","volume":"73","author":"Green","year":"2016","journal-title":"J Infect"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-023-02148-y","article-title":"High prevalence of Pneumocystis pneumonia in interstitial lung disease: a retrospective study","volume":"52","author":"Liu","year":"2024","journal-title":"Infection"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.4.1536-1538.2000","article-title":"Transmission of Pneumocystis carinii DNA from a patient with P. carinii pneumonia to immunocompetent contact health care workers","volume":"38","author":"Vargas","year":"2000","journal-title":"J Clin Microbiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100400","DOI":"10.1016\/j.lanepe.2022.100400","article-title":"Evolving epidemiology of Pneumocystis pneumonia: Findings from a longitudinal population-based study and a retrospective multi-center study in Germany","volume":"18","author":"Kolbrink","year":"2022","journal-title":"Lancet Reg Health Eur"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2023.02.014","article-title":"Rising incidence of Pneumocystis pneumonia: A population-level descriptive ecological study in England","volume":"86","author":"Pates","year":"2023","journal-title":"J Infect"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201807-1358ED","article-title":"In Search of Clinical Factors that Predict Risk for Pneumocystis jirovecii Pneumonia in Patients without HIV\/AIDS","volume":"198","author":"Limper","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2024.01.015","article-title":"Characteristics and prognosis factors of Pneumocystis jirovecii pneumonia according to underlying disease: A retrospective multicenter study","volume":"165","author":"Lecuyer","year":"2024","journal-title":"Chest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2016.03.018","article-title":"Pneumocystis pneumonia suspected cases in 604 non-HIV and HIV patients","volume":"46","author":"Bienvenu","year":"2016","journal-title":"Int J Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.5.1204","article-title":"Pneumocystis carinii pneumonia. 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