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Toll-like Receptor-4 (TLR4) Agonist-Based Intranasal Nanovaccine Delivery System for Inducing Systemic and Mucosal Immunity.
Bakkari, Mohammed Ali; Valiveti, Chaitanya K; Kaushik, Radhey S; Tummala, Hemachand.
  • Bakkari MA; Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, South Dakota State University, Brookings, South Dakota 57007, United States.
  • Valiveti CK; College of Pharmacy, Jazan University, Jazan 45142, Kingdom of Saudi Arabia.
  • Kaushik RS; Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, South Dakota State University, Brookings, South Dakota 57007, United States.
  • Tummala H; Department of Biology and Microbiology, South Dakota State University, Brookings, South Dakota57007, United States.
Mol Pharm ; 18(6): 2233-2241, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1233685
ABSTRACT
Eliciting a robust immune response at mucosal sites is critical in preventing the entry of mucosal pathogens such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This task is challenging to achieve without the inclusion of a strong and safe mucosal adjuvant. Previously, inulin acetate (InAc), a plant-based polymer, is shown to activate toll-like receptor-4 (TLR4) and elicit a robust systemic immune response as a vaccine adjuvant. This study investigates the potential of nanoparticles prepared with InAc (InAc-NPs) as an intranasal vaccine delivery system to generate both mucosal and systemic immune responses. InAc-NPs (∼250 nm in diameter) activated wild-type (WT) macrophages but failed to activate macrophages from TLR4 knockout mice or WT macrophages when pretreated with a TLR4 antagonist (lipopolysaccharide-RS (LPS-RS)), which indicates the selective nature of a InAc-based nanodelivery system as a TLR4 agonist. Intranasal immunization using antigen-loaded InAc-NPs generated ∼65-fold and 19-fold higher serum IgG1 and IgG2a titers against the antigen, respectively, as compared to PLGA-NPs as a delivery system. InAc-NPs have also stimulated the secretion of sIgA at various mucosal sites, including nasal-associated lymphoid tissues (NALTs), lungs, and intestine, and produced a strong memory response indicative of both humoral and cellular immune activation. Overall, by stimulating both systemic and mucosal immunity, InAc-NPs laid a basis for a potential intranasal delivery system for mucosal vaccination.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Carriers / Adjuvants, Immunologic / COVID-19 Vaccines / COVID-19 / Inulin Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Humans / Male Language: English Journal: Mol Pharm Journal subject: Molecular Biology / Pharmacy / Pharmacology Year: 2021 Document Type: Article Affiliation country: Acs.molpharmaceut.0c01256

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Carriers / Adjuvants, Immunologic / COVID-19 Vaccines / COVID-19 / Inulin Type of study: Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Humans / Male Language: English Journal: Mol Pharm Journal subject: Molecular Biology / Pharmacy / Pharmacology Year: 2021 Document Type: Article Affiliation country: Acs.molpharmaceut.0c01256