Using an Aluminum Hydroxide–Chitosan Matrix Increased the Vaccine Potential and Immune Response of Mice against Multi-Drug-Resistant Acinetobacter baumannii

Author:

Deusdará Túllio T.1ORCID,Félix Mellanie K. C.1,de S. Brito Helio1ORCID,Cangussu Edson W. S.2,de S. Moura Wellington1ORCID,Albuquerque Benedito2,Silva Marcos G.2,dos Santos Gil R.12ORCID,de Morais Paula B.1ORCID,da Silva Elizangela F.3,Chaves Yury O.3,Mariúba Luis Andre M.3,Nogueira Paulo A.3,Astolfi-Filho Spartaco4,Assunção Enedina N.4,Epiphanio Sabrina5ORCID,Marinho Claudio R. F.5,Brandi Igor V.67ORCID,Viana Kelvinson F.8,Oliveira Eugenio E.29ORCID,Cangussu Alex Sander R.12

Affiliation:

1. Graduate Program for Biodiversity and Biotechnology of Legal Amazon, Federal University of Tocantins, Palmas 77001-090, TO, Brazil

2. Graduate Program in Biotechnology, Federal University of Tocantins, Gurupi 77425-000, TO, Brazil

3. Instituto Leônidas e Maria Deane, Oswaldo Cruz Foundation-Fiocruz Amazônia, Manaus 69057-070, AM, Brazil

4. Laboratory of DNA Technology, Biotechnology Department, Multidisciplinary Support Center, Federal University of Amazonas, Manaus 69080-900, AM, Brazil

5. Department of Immunology, Biomedical Science Institute, University of São Paulo (USP), São Paulo 05508-060, SP, Brazil

6. Institute of Agricultural Sciences, Federal University of Minas Gerais, Montes Claros 39400-310, MG, Brazil

7. Department of Biotchnology, State University of Montes Claros, Montes Claros 39401-089, MG, Brazil

8. Interdisciplinary Center for Life Sciences and Nature, Federal University of Latin American Integration (UNILA), Foz do Iguaçu 85866-000, PR, Brazil

9. Departamento de Entomologia, Universidade Federal de Viçosa, Viçosa 36570-900, MG, Brazil

Abstract

Acinetobacter baumannii is a Gram-negative, immobile, aerobic nosocomial opportunistic coccobacillus that causes pneumonia, septicemia, and urinary tract infections in immunosuppressed patients. There are no commercially available alternative antimicrobials, and multi-drug resistance is an urgent concern that requires emergency measures and new therapeutic strategies. This study evaluated a multi-drug-resistant A. baumannii whole-cell vaccine, inactivated and adsorbed on an aluminum hydroxide–chitosan (mAhC) matrix, in an A. baumannii sepsis model in immunosuppressed mice by cyclophosphamide (CY). CY-treated mice were divided into immunized, non-immunized, and adjuvant-inoculated groups. Three vaccine doses were given at 0D, 14D, and 28D, followed by a lethal dose of 4.0 × 108 CFU/mL of A. baumannii. Immunized CY-treated mice underwent a significant humoral response, with the highest IgG levels and a higher survival rate (85%); this differed from the non-immunized CY-treated mice, none of whom survived (p < 0.001), and from the adjuvant group, with 45% survival (p < 0.05). Histological data revealed the evident expansion of white spleen pulp from immunized CY-treated mice, whereas, in non-immunized and adjuvanted CY-treated mice, there was more significant organ tissue damage. Our results confirmed the proof-of-concept of the immune response and vaccine protection in a sepsis model in CY-treated mice, contributing to the advancement of new alternatives for protection against A. baumannii infections.

Funder

ASRC

CRFM

SE

EEO

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Exploration of chitosan and its modified derivatives as vaccine adjuvant: A review;Carbohydrate Polymer Technologies and Applications;2024-12

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