Recombinant Aspergillus fumigatus antigens Asp f 3 and Asp f 9 in liposomal vaccine protect mice against invasive pulmonary aspergillosis.

Autor: Slarve M; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Holznecht N; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Reza H; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Gilkes A; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Slarve I; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Olson J; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Ernst W; Molecular Express, Inc, Rancho Dominguez, CA, United States., Ho SO; Molecular Express, Inc, Rancho Dominguez, CA, United States., Adler-Moore J; California State Polytechnic University, Pomona, Biological Sciences Department, Pomona, CA, United States., Fujii G; Molecular Express, Inc, Rancho Dominguez, CA, United States.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2022 Jul 29; Vol. 40 (31), pp. 4160-4168. Date of Electronic Publication: 2022 Jun 06.
DOI: 10.1016/j.vaccine.2022.05.057
Abstrakt: Invasive pulmonary aspergillosis caused by the ubiquitous mold Aspergillus fumigatus is a major threat to immunocompromised patients, causing unacceptably high mortality despite standard of care treatment, and costing an estimated $1.2 billion annually. Treatment for this disease has been complicated by the emergence of azole resistant strains of A. fumigatus, rendering first-line antifungal therapy ineffective. The difficulties in treating infected patients using currently available drugs make immunotherapeutic vaccination an attractive option. Here, we demonstrate the efficacy of VesiVax® adjuvant liposomes, consisting of a combination of two individual liposome preparations, to which two recombinant A. fumigatus surface antigens, Asp f 3 and Asp f 9 (VesiVax® Af3/9), have been chemically conjugated. Using a murine model, we demonstrate that VesiVax® Af3/9 is protective against infection by azole resistant strains of A. fumigatus in both steroid-suppressed and neutropenic mice as quantified by improved survival and reduced fungal burden in the lungs. This protection correlates with upregulation of IL-4 produced by splenocytes, and the presence of Asp f 3 and Asp f 9 specific IgG2a antibodies in the serum of mice given VesiVax® Af3/9. Furthermore, mice given VesiVax® Af3/9 with a subsequent course of liposomal amphotericin B (AmBisome®) had improved survival over those given either treatment alone, indicating a benefit to VesiVax® Af3/9 vaccination even in the case of infections that require follow-up antifungal treatment. These data demonstrate that prophylactic vaccination with VesiVax® Af3/9 is a promising method of protection against invasive pulmonary aspergillosis even as the changing face of the disease renders current therapies ineffective.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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