Development of an Intranasal Gel for the Delivery of a Broadly Acting Subunit Influenza Vaccine.
Devika M. Varma,Cole J. Batty,Rebeca T Stiepel,Elizabeth G. Graham-Gurysh,John Roque,Erik S Pena,M. S. Hasan Zahid,Kunyu Qiu,Aaron C. Anselmo,David B. Hill,Ted M. Ross,Eric M. Bachelder,Kristy M. Ainslie +12 more
TLDR
Overall, this study indicates the utility of an intranasal gel for the delivery of COBRAs for the generation of serum and mucosal humoral responses.Abstract:
Influenza virus is a major cause of death on a global scale. Seasonal vaccines have been developed to combat influenza; however, they are not always highly effective. One strategy to develop a more broadly active influenza vaccine is the use of multiple rounds of layered consensus buildings to generate recombinant antigens, termed computationally optimized broadly reactive antigen (COBRA). Immunization with the COBRA hemagglutinin (HA) can elicit broad protection against multiple strains of a single influenza subtype (e.g., H1N1). We formulated a COBRA H1 HA with a stimulator of interferon genes agonist cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) into a nasal gel for vaccination against influenza. The gel formulation was designed to increase mucoadhesion and nasal retention of the antigen and adjuvant to promote a strong mucosal response. It consisted of a Schiff base-crosslinked hydrogel between branched polyethyleneimine and oxidized dextran. Following a prime-boost-boost schedule, an intranasal gel containing cGAMP and model antigen ovalbumin (OVA) led to the faster generation of serum IgG, IgG1, and IgG2c and significantly greater serum IgG1 levels on day 42 compared to soluble controls. Additionally, OVA-specific IgA was detected in nasal, vaginal, and fecal samples for all groups, except the vehicle control. When the COBRA HA was given intranasally in a prime-boost schedule, the mice receiving the gel containing the COBRA and cGAMP had significantly higher serum IgG and IgG2c at day 41 compared to all groups, and only this group had IgA levels above the background in vaginal, nasal, and fecal samples. Overall, this study indicates the utility of an intranasal gel for the delivery of COBRAs for the generation of serum and mucosal humoral responses.read more
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Mucosal immune responses to infection and vaccination in the respiratory tract
TL;DR: Hewitt et al. as discussed by the authors reviewed the innate and adaptive immune responses in the lung and airways following infection and vaccination, with particular focus on influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant.
Matthew D. Gallovic,Robert D. Junkins,Adam Sandor,Erik S Pena,Christopher J. Sample,Ariel K Mason,Leslee Arwood,Rebecca A Sahm,Eric M. Bachelder,Kristy M. Ainslie,Gregory D. Sempowski,Jenny P.-Y. Ting +11 more
TL;DR: In this article , the authors used an adjuvant comprised of a Stimulator of Interferon Genes (STING) agonist incorporated in a scalable microparticle platform to achieve durable protection against the influenza virus.
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Vinyl Sulfone-functionalized Acetalated Dextran Microparticles as a Subunit Broadly Acting Influenza Vaccine
Cole J. Batty,Liubov M. Lifshits,Dylan Hendy,Meital Eckshtain-Levi,Luis Alberto Ontiveros-Padilla,Michael A. Carlock,Ted M. Ross,Eric M. Bachelder,Kristy M. Ainslie +8 more
TL;DR: In this article , the ACE-DEX microparticles (MPs) were used to conjugate COBRA to the surface and encapsulate the STING agonist cGAMP to form a broadly active influenza vaccine.
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cGAMP the travelling messenger
Henry T. W. Blest,Lise Chauveau +1 more
TL;DR: In this article , the authors describe the fast-paced discovery of the mechanisms by which 2'3'-cGAMP can be transported and highlight the diseases where they are important and detail how this change in perspective can be applied to vaccine design, cancer immunotherapies and treatment of cGAS-STING associated disease.
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Hydrogels for Mucosal Drug Delivery.
TL;DR: In this paper, the authors discuss hydrogels as an attractive means for local delivery of therapeutics to address a range of conditions affecting the eye, nose, oral cavity, gastrointestinal, urinary bladder, and vaginal tracts.
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