Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

Abstract

H5N1 avian influenza is a significant global concern with the potential to become the next pandemic threat. Recombinant subunit vaccines are an attractive alternative for pandemic vaccines compared to traditional vaccine technologies. In particular, polyanhydride nanoparticles encapsulating subunit proteins have been shown to enhance humoral and cell-mediated immunity and provide protection upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H5 3 ) was produced and encapsulated into polyanhydride nanoparticles. The studies performed indicated that the recombinant H5 3 antigen was a robust immunogen. Immunizing mice with H5 3 encapsulated into polyanhydride nanoparticles induced high neutralizing antibody titers and enhanced CD4 + T cell recall responses in mice. Finally, the H5 3 -based polyanhydride nanovaccine induced protective immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses indicated that mice receiving the nanovaccine formulations and subsequently challenged with virus were similar to naïve mice that were not challenged. The current studies provide a basis to further exploit the advantages of polyanhydride nanovaccines in pandemic scenarios.

The effect of polyanhydride chemistry in particle-based cancer vaccines on the magnitude of the anti-tumor immune response

“…Such results are in contrast to those obtained with poly(lactic-co-glycolic acid) and poly(diaminosulfide) particles co-encapsulating OVA and CpG ODN where CpG ODN was reported to enhance the immunogenicity of these formulations [18, 21, 69]. These studies add to the body of literature attesting to the inherent adjuvanticity exhibited by polyanhydride particles [19, 20, 36–47]. …”

“…Furthermore, since polyanhydrides are inert and their degradation products are safe, they have high biocompatibility and are suitable for in vivo drug/antigen delivery [24]. Additionally, polyanhydrides have been reported to have inherent adjuvant properties and polyanhydride particles can act as Toll-like receptor (TLR) agonists on various TLRs including TLRs 2, 4, and 5 [19, 20, 36–47]. …”

Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf

“… 26 , 29 – 31 . Finally, these nanoadjuvants have been shown to induce sustained humoral 32 and cellular immunity 33 , 34 . These properties have been exploited to design nanovaccine formulations against multiple pathogens, including Yersinia pestis , Bacillus anthracis , Streptococcus pneumoniae , and influenza A virus 18 .…”

Poly-γ-glutamic acid/chitosan nanogel greatly enhances the efficacy and heterosubtypic cross-reactivity of H1N1 pandemic influenza vaccine

“…For the clinical application, most of nanoparticle-based adjuvants have potential limitations such as insufficient efficacy, difficult manufacturing, unacceptable toxicity, and economic feasibility. PC nanogel adjuvated vaccine induced earlier virus clearance after heterosubtypic virus challenges in mice model, which had not been reported in most of other nanoparticle-based adjuvants containing poly(lactide-co-glycolide), polyanhydrides, polypropylene sulfide and liposome545556. In the fabrication point of view, the PC nanogels were easily manufactured by the electrostatic interaction between two bio-derived polymeric components, γ-PGA and chitosan11.…”