Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and Confers Protection Against Homologous and Heterologous Influenza A Virus Infections

Abstract

Influenza A virus (IAV) is a major cause of respiratory illness. Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious “universal” IAV vaccination strategies. Recent studies have highlighted that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters. Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections. Herein, we report on an intranasally administered biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax) capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations. Our findings also demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs, both systemic and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4 and CD8 T cells. Altogether our findings show that an intranasally administered nanovaccine can induce immunity within the lungs, similar to what occurs during IAV infections, and thus could prove useful as a strategy for providing “universal” protection against IAV.

Single dose combination nanovaccine provides protection against influenza A virus in young and aged mice

“…In this regard, intranasal IAV nanovaccines have been shown to induce local and systemic immunity resulting in protection against both homologous and heterologous IAV challenge. 18 Thus, vaccination strategies that allow for intranasal administration of combination nanovaccines and enhance mucosal immunity in older adults may be explored in future studies.…”

“…In particular, polyanhydride nanoparticles have been demonstrated to provide sustained release of encapsulated influenza antigens while enhancing antigen stability. 17 In addition, polyanhydridebased nanovaccines have been shown to induce antihemagglutinin (HA) antibody titers capable of neutralizing influenza virus, inducing antigen-specific CD4 + and CD8 + T cell responses, including lung-resident memory phenotypes 18 and providing protection against challenge. 4 Similarly, pentablock copolymers based on Pluronic F127 and polydiethylaminoethyl methacrylate (PDEAEM) represent another effective platform for affording sustained release of antigen, depositing the antigen in the cytosol, and promoting the rapid development of antibody titers.…”

Pentablock Copolymer Micelle Nanoadjuvants Enhance Cytosolic Delivery of Antigen and Improve Vaccine Efficacy while Inducing Low Inflammation

“…Since the PBC micelle concentration used in the present studies do not form a depot at the injection site, unlike the hydrogels, we hypothesize that the observed enhancement in humoral immunity may be attributed to the association of the antigen and the PBC micelles. There is significant interest in designing vaccine carriers to enhance cytosolic uptake of antigens resulting in enhanced presentation via the MHC I pathway and induction of CD8 + T cell responses 53,59 .…”

A single dose polyanhydride-based nanovaccine against paratuberculosis infection

“…This is likely induced by the inclusion of polyanhydride nanoparticles in the PAN-Cf group, consistent with previous observations. 61,62 The nanoparticle chemistry used in this study (i.e., 20:80 CPTEG: CPH) was rationally selected based on previous reports showing its potency as an adjuvant as exhibited by robust induction of cellular immune responses. 35 Similarly, in this study PAN-Cf vaccinated mice at pre-challenge not only induced a polyfunctional CD8 + T cell response but also had more breadth as indicated by induction of more types of cytokine secreting cells.…”