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A SpA+LukAB vaccine targeting Staphylococcus aureus evasion factors restricts infection in two minipig infection models.

作者信息

Poolman Jan T, Torres Victor J, Missiakas Dominique, Welten Suzanne P M, Fernandez Jeffrey, DuMont Ashley L, O'Keeffe Anna, Konstantinov Sergey R, Morrow Brian, Burghout Peter, Grijpstra Jan, van Beers Miranda M C, Anish Chakkumkal, Beurret Michel, Geurtsen Jeroen, Rood Pauline M L, Koeberling Oliver, Shi Miaomiao, van den Dobbelsteen Germie P J M

机构信息

Bacterial Vaccines Discovery and Early Development, Janssen Vaccines and Prevention B.V Archimedesweg 4-6, Leiden, The Netherlands.

Department of Microbiology, New York University School of Medicine, Alexandria Center for Life Science, New York, NY, USA.

出版信息

NPJ Vaccines. 2025 Apr 20;10(1):78. doi: 10.1038/s41541-025-01119-8.

DOI:10.1038/s41541-025-01119-8
PMID:40254611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12009994/
Abstract

Staphylococcus aureus is a major cause of bacterial infection-related deaths. Increasing antimicrobial resistance highlights the urgent need for effective preventative strategies. Antibody-mediated opsonophagocytosis, the key mechanism for protection against S. aureus, is disabled by critical virulence factors such as Staphylococcal protein A (SpA) and leukocidin AB (LukAB). In our study, we combined genetically detoxified vaccine candidates SpA* and LukAB RARPR-33 with a T1 adjuvant aiming to restore host antibody functionality. To evaluate these vaccine candidates, we developed both surgical site infection (SSI) and superficial wound infection (SWI) models in minipigs. Our results showed a significant reduction in bacterial load and systemic dissemination in the SSI model, while skin infection severity was markedly decreased after intradermal immunization in the SWI model. This study introduces a novel S. aureus vaccine strategy by targeting immune evasion factors SpA and LukAB, utilizing potent T1 adjuvants, and employing minipig challenge models.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/22b3738af5a5/41541_2025_1119_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/434343f65f63/41541_2025_1119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/d436cd9c91d2/41541_2025_1119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/26220ef3d7c6/41541_2025_1119_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/f4151d89de4e/41541_2025_1119_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/dac12703d2b7/41541_2025_1119_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/266e851f3dd1/41541_2025_1119_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/715d01697ccb/41541_2025_1119_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/263940a4ec71/41541_2025_1119_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/6b24ccdd0115/41541_2025_1119_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/fb9ea13c1f46/41541_2025_1119_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/22b3738af5a5/41541_2025_1119_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/434343f65f63/41541_2025_1119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/d436cd9c91d2/41541_2025_1119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/26220ef3d7c6/41541_2025_1119_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/f4151d89de4e/41541_2025_1119_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/dac12703d2b7/41541_2025_1119_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/266e851f3dd1/41541_2025_1119_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/715d01697ccb/41541_2025_1119_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/263940a4ec71/41541_2025_1119_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/6b24ccdd0115/41541_2025_1119_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/fb9ea13c1f46/41541_2025_1119_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c15/12009994/22b3738af5a5/41541_2025_1119_Fig11_HTML.jpg

相似文献

[1]
A SpA+LukAB vaccine targeting Staphylococcus aureus evasion factors restricts infection in two minipig infection models.

NPJ Vaccines. 2025-4-20

[2]
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Cochrane Database Syst Rev. 2017-5-18

[3]
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[4]
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[6]
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[7]
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[8]
Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) related complications in surgical patients.

Cochrane Database Syst Rev. 2013-8-19

[9]
Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model.

J Infect Dis. 2022-4-19

[10]
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引用本文的文献

[1]
in Livestock: Molecular Epidemiology, Antimicrobial Resistance, and Translational Strategies for One Health Protection.

Vet Sci. 2025-8-13

[2]
in Foodborne Diseases and Alternative Intervention Strategies to Overcome Antibiotic Resistance by Using Natural Antimicrobials.

Microorganisms. 2025-7-24

[3]
Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.

Nat Rev Microbiol. 2025-8-20

本文引用的文献

[1]
The immune evasion roles of protein A and impact on vaccine development.

Front Cell Infect Microbiol. 2023-9-27

[2]
Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial.

Clin Infect Dis. 2023-7-26

[3]
Assessing the generation of tissue resident memory T cells by vaccines.

Nat Rev Immunol. 2023-10

[4]
Skin-Based Vaccination: A Systematic Mapping Review of the Types of Vaccines and Methods Used and Immunity and Protection Elicited in Pigs.

Vaccines (Basel). 2023-2-16

[5]
Staphylococcus aureus host interactions and adaptation.

Nat Rev Microbiol. 2023-6

[6]
adaptive evolution: Recent insights on how immune evasion, immunometabolic subversion and host genetics impact vaccine development.

Front Cell Infect Microbiol. 2022

[7]
Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019.

Lancet. 2022-12-17

[8]
Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.

Lancet. 2022-2-12

[9]
Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies.

Front Immunol. 2021

[10]
A protein A based Staphylococcus aureus vaccine with improved safety.

Vaccine. 2021-6-29

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