Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

Wilson, Kirsty L.; Howard, Gregory P.; Coatsworth, Heather; Dinglasan, Rhoel R.; Mao, Hai-Quan; Plebanski, Magdalena

doi:10.3390/vaccines8020261

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Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

^1,2,†,

^3,4,†

⁵,

^5,*

^3,4,6,* and

^1,2,*

School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Victoria 3084, Australia

Department of Immunology and Pathology, Monash University, Melbourne, Victoria 3181, Australia

Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

⁴

Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA

⁵

Emerging Pathogens Institute, Department of Infectious Diseases & Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA

⁶

Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA

Authors to whom correspondence should be addressed.

^†

Authors contributed equally to this work.

Vaccines 2020, 8(2), 261; https://doi.org/10.3390/vaccines8020261

Received: 23 March 2020 / Revised: 20 May 2020 / Accepted: 25 May 2020 / Published: 29 May 2020

(This article belongs to the Section Vaccine Adjuvants)

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Abstract

Sustained immune responses, particularly antibody responses, are key for protection against many endemic infectious diseases. Antibody responses are often accompanied by T helper (Th) cell immunity. Herein we study small biodegradable poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) nanoparticles (PEG-b-PLGA NPs, 25–50 nm) as antigen- or adjuvant-carriers. The antigen carrier function of PEG-b-PLGA NPs was compared against an experimental benchmark polystyrene nanoparticles (PS NPs, 40–50 nm), both conjugated with the model antigen ovalbumin (OVA-PS NPs, and OVA-PEG-b-PLGA NPs). The OVA-PEG-b-PLGA NPs induced sustained antibody responses to Day 120 after two immunizations. The OVA-PEG-b-PLGA NPs as a self-adjuvanting vaccine further induced IL-4 producing T-helper cells (Th2), but not IFN-γ producing T-cells (Th1). The PEG-b-PLGA NPs as a carrier for CpG adjuvant (CpG-PEG-b-PLGA NPs) were also tested as mix-in vaccine adjuvants comparatively for protein antigens, or for protein-conjugated to PS NPs or to PEG-b-PLGA NPs. While the addition of this adjuvant NP did not further increase T-cell responses, it improved the consistency of antibody responses across all immunization groups. Together these data support further development of PEG-b-PLGA NPs as a vaccine carrier, particularly where it is desired to induce Th2 immunity and achieve sustained antibody titers in the absence of affecting Th1 immunity. View Full-Text

Keywords: nanoparticle; adjuvant; vaccine; antibody; immune response

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MDPI and ACS Style

Wilson, K.L.; Howard, G.P.; Coatsworth, H.; Dinglasan, R.R.; Mao, H.-Q.; Plebanski, M. Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation. Vaccines 2020, 8, 261. https://doi.org/10.3390/vaccines8020261

AMA Style

Wilson KL, Howard GP, Coatsworth H, Dinglasan RR, Mao H-Q, Plebanski M. Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation. Vaccines. 2020; 8(2):261. https://doi.org/10.3390/vaccines8020261

Chicago/Turabian Style

Wilson, Kirsty L., Gregory P. Howard, Heather Coatsworth, Rhoel R. Dinglasan, Hai-Quan Mao, and Magdalena Plebanski. 2020. "Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation" Vaccines 8, no. 2: 261. https://doi.org/10.3390/vaccines8020261

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Biodegradable PLGA-b-PEG Nanoparticles Induce T Helper 2 (Th2) Immune Responses and Sustained Antibody Titers via TLR9 Stimulation

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