Improved Humoral Immunity and Protection against Influenza Virus Infection with a 3d Porous Biomaterial Vaccine.

Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE

Original Publication: Weinheim : WILEY-VCH, [2014]-

Influenza, Human* ; Influenza Vaccines* ; Orthomyxoviridae* ; Orthomyxoviridae Infections*; Animals ; Mice ; Humans ; Immunity, Humoral ; Porosity ; Antibodies, Viral ; Antigens

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4 ⁺ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness and antigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross-linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

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R01 AR073912 United States NH NIH HHS; R01-AR073912 United States AR NIAMS NIH HHS; R01 AR073912 United States AR NIAMS NIH HHS; R01-AR079470-01 United States NH NIH HHS; T32 AI125185 United States AI NIAID NIH HHS; 2 T32AI125185 United States NH NIH HHS; R01 AR079470 United States AR NIAMS NIH HHS

Keywords: biomaterial; immunomodulation; influenza; microfluidics; vaccine

34S289N54E (aluminum sulfate)
0 (Influenza Vaccines)
0 (Antibodies, Viral)
0 (Antigens)

Date Created: 20230926 Date Completed: 20231106 Latest Revision: 20240210

20240210

PMC10625058

10.1002/advs.202302248

37750461