Bioengineered metastatic cancer nanovaccine with a TLR7/8 agonist for needle-free intranasal immunization

Abstract

Recent outbreaks and the global spread of infectious diseases increased the need for the development of mucosal vaccines because of their ability to induce both an antigen-specific humoral and cellular immune response. Vaccines are commonly administered via a systemic route which is ineffective at inducing mucosal immunity. Therefore, developing mucosal vaccines is necessary to prevent and treat diseases that could not only elicit mucosal immune responses but also facilitate mass vaccination via a needle-free approach. Despite the benefits of mucosal vaccines, inducing mucosal immunity remains difficult due to the low antigen stability at mucosal sites. Herein, we developed a co-delivery platform using a polymeric nanoparticle carrier to upregulate the immune responses by improving the antigen's stability. Through hydrophobic and ionic interactions, the cationic polymeric nanoparticle composed of secondary bile acid conjugated polyethyleneimine (DA3) can load both TLR7/8 agonist resiquimod (R848) and anionic ovalbumin (OVA) antigen. The DA3/R848/OVA nanovaccine based co-delivery system can boost immune responses through binding affinity with dendritic cells (DCs). The results showed that DA3/R848/OVA could activate DCs better than OVA or OVA + R848. Furthermore, the nanovaccine demonstrated a strong therapeutic effect by significantly suppressing tumor growth in a B16-OVA melanoma model. Additionally, prophylactic immunization with the nanovaccine effectively induced immunological memory, leading to sustained tumor suppression upon challenge. Intranasal delivery of DA3/R848/OVA upregulates the antitumor effect in the metastatic lung tumor foci and the survival rates. These results suggest that intranasal immunization using the DA3/R848/OVA nanovaccine can promote needle-free vaccination.

Keywords: Intranasal delivery; Metastasis; Nanoparticles; Needle-free vaccination; Resiquimod.