Hemagglutinin Functionalized Liposomal Vaccines Enhance Germinal Center and Follicular Helper T Cell Immunity.
Mai N VuHannah G KellyHyon-Xhi TanJennifer A JunoRobyn EsterbauerThomas P DavisNghia Phuoc TruongAdam K WheatleyStephen J KentPublished in: Advanced healthcare materials (2021)
Despite remarkable successes of immunization in protecting public health, safe and effective vaccines against a number of life-threatening pathogens such as HIV, ebola, influenza, and SARS-CoV-2 remain urgently needed. Subunit vaccines can avoid potential toxicity associated with traditional whole virion-inactivated and live-attenuated vaccines; however, the immunogenicity of subunit vaccines is often poor. A facile method is here reported to produce lipid nanoparticle subunit vaccines that exhibit high immunogenicity and elicit protection against influenza virus. Influenza hemagglutinin (HA) immunogens are functionalized on the surface of liposomes via stable metal chelation chemistry, using a scalable advanced microfluidic mixing technology (NanoAssemblr). Immunization of mice with HA-liposomes elicits increased serum antibody titers and superior protection against highly pathogenic virus challenge compared with free HA protein. HA-liposomal vaccines display enhanced antigen deposition into germinal centers within the draining lymph nodes, driving increased HA-specific B cell, and follicular helper T cell responses. This work provides mechanistic insights into highly protective HA-liposome vaccines and informs the rational design and rapid production of next generation nanoparticle subunit vaccines.
Keyphrases
- sars cov
- public health
- lymph node
- drug delivery
- quantum dots
- antiretroviral therapy
- hiv infected
- dendritic cells
- single cell
- risk assessment
- early stage
- immune response
- hepatitis c virus
- gold nanoparticles
- multidrug resistant
- adipose tissue
- neoadjuvant chemotherapy
- high resolution
- hiv positive
- men who have sex with men
- high fat diet induced
- protein protein
- loop mediated isothermal amplification
- oxide nanoparticles
- label free