Nanoparticle-Based Antivirulence Vaccine for the Management of Methicillin-ResistantStaphylococcus aureusSkin Infection.
With the rising threat of antibiotic-resistant bacteria, vaccination is becoming an increasingly important strategy to prevent and manage bacterial infections. Made from deactivated bacterial toxins, toxoid vaccines are widely used in the clinic as they help to combat the virulence mechanisms employed by different pathogens. Herein, the efficacy of a biomimetic nanoparticle-based anti-virulence vaccine is examined in a mouse model of methicillin-resistantStaphylococcus aureus(MRSA) skin infection. Vaccination with nanoparticle-detained staphylococcal α-hemolysin (Hla) effectively triggers the formation of germinal centers and induces high anti-Hla titers. Compared to mice vaccinated with control samples, those vaccinated with the nanoparticle toxoid show superior protective immunity against MRSA skin infection. The vaccination not only inhibits lesion formation at the site of bacterial challenge, but also reduces the invasiveness of MRSA, preventing dissemination into other organs. Overall, this biomimetic nanoparticle-based toxin detainment strategy is a promising method for the design of potent anti-virulence vaccines for managing bacterial infections.
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A. Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
Fei
F
Wang
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Ronnie H
RH
Fang
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Brian T
BT
Luk
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Che-Ming J
CJ
Hu
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Soracha
S
Thamphiwatana
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Diana
D
Dehaini
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Pavimol
P
Angsantikul
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Ashley V
AV
Kroll
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A. Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
Zhiqing
Z
Pang
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Weiwei
W
Gao
Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
Weiyue
W
Lu
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, U.S.A.
Liangfang
L
Zhang
MRSA infection; anti-virulence vaccination; biomimetic nanoparticle; toxoid; α-hemolysin