In:
Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
Abstract:
Rise in multi-drug-resistance (MDR) among pathogens and increasing populations at risk for these infections raises the threat of nearly untreatable infectious diseases. Thus, novel vaccine strategies to prevent and/or treat MDR pathogens would benefit global health immensely. Candida albicans (CA) cell wall proteins Als3p and Hyr1p protect against candidemia due to CA and MDR C. auris (CAU). Further, Hyr1p shares structural homology with conserved hemagglutinin (FhaB) and OmpA proteins in many Gram-negative bacteria (GNB) Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA). Thus, Hyr1p antigen-based active and passive vaccinations protect against AB and KP pneumonia. We hypothesized that a dual Als3p/Hyr1p antigen vaccine formulated with CAF01 (a clinical stage adjuvant) that can promote a balanced Th1/Th2/Th17 immune response is likely to protect against multiple healthcare-associated infections caused by Candida species and MDR GNB. Methods To formulate Als3p/Hyr1p antigen, we mixed CAF01 with Als3p and Hyr1p antigens in the following ratios: 0/0, 10/10, 10/30, 30/10 and 30/3 µg for each dose. CD-1 mice with each dose subcutaneously, followed by booster immunization on day 21. For efficacy evaluation, vaccinated mice (n=20 mice/group) were immunosuppressed by administration of cyclophosphamide and cortisone acetate on day -2 and +3, relative to infection with either CAU, AB, KP or PA. Infection occurred two weeks following the booster immunization. For, CA infection, immunocompetent mice were infected intravenously two weeks following a primary booster or after a second booster given on day 35. Results All Als3p/Hyr1p formulations induced robust immunity against both antigens. For CA infection, two booster immunizations provide superior protection over one booster immunization. For CAU and GNB, one booster dose was enough to provide significant protection. Further, both 30/10 and 10/10 vaccine formulations protected significantly against all five infections. Specifically, for fungal infections, 30/10 and 10/10 formulations showed 30-40% and 40-50% survival efficacies (vs. 0% for placebo), respectively. TABLE 1. Survival efficacy of Als3p/Hyr1p formulations against Candida species and Gram-negative bacterial infections. Conclusion Our study shows that the Als3p/Hyr1p induced a robust protective immunity against CA, MDR CAU and GNB. Disclosures All Authors: No reported disclosures.
Type of Medium:
Online Resource
ISSN:
2328-8957
DOI:
10.1093/ofid/ofac492.175
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2022
detail.hit.zdb_id:
2757767-3
