Abstract
Chitosan nanoparticles (CNPs) represent an efficient vaccination tool to deliver immunogenic antigens to the antigen-presenting cells (APCs), which subsequently stimulate protective immune responses against infectious diseases. Herein, we prepared CNPs encapsulating mRNA molecules followed by surface coating with conserved H9N2 HA2 and M2e influenza proteins. We demonstrated that CNPs efficiently delivered mRNA molecules into APCs and had effectively penetrated the mucosal barrier to reach to the immune initiation sites. To investigate the potential of CNPs delivering influenza antigens to stimulate protective immunity, we intranasally vaccinated chickens with empty CNPs, CNPs delivering HA2 and M2e in both mRNA and protein formats (CNPs + RNA + Pr) or CNPs delivering antigens in protein format only (CNPs + Pr). Our results demonstrated that chickens vaccinated with CNPs + RNA + Pr elicited significantly (p < 0.05) higher systemic IgG, mucosal IgA antibody responses and cellular immune responses compared to the CNPs + Pr vaccinated group. Consequently, upon challenge with either H7N9 or H9N2 avian influenza viruses (AIVs), efficient protection, in the context of viral load and lung pathology, was observed in chickens vaccinated with CNPs + RNA + Pr than CNPs + Pr vaccinated group. In conclusion, we show that HA2 and M2e antigens elicited a broad spectrum of protection against AIVs and incorporation of mRNAs in vaccine formulation is an effective strategy to induce superior immune responses.
Highlights
Avian influenza viruses (AIVs), broadly designated as highly pathogenic avian influenza (HPAI) or low pathogenic avian influenza (LPAI), annually cause significant economic losses in the poultry industry worldwide [1, 2]
Concerning the H7N9 challenge, our results indicated that chickens that received chitosan nanoparticles (CNP) delivering antigens in both protein plus mRNA formats elicited significantly (p < 0.001) higher virus neutralization titers (VNT) compared to the group that received CNPs delivering protein only, which showed VNT comparable to that of the control group challenged with the H7N9 virus
Hereby we anticipate a rapid presentation of antigens loaded on the surface of CNPs and subsequent release of mRNA into the antigen-presenting cells (APCs) upon particle acquisition
Summary
Avian influenza viruses (AIVs), broadly designated as highly pathogenic avian influenza (HPAI) or low pathogenic avian influenza (LPAI), annually cause significant economic losses in the poultry industry worldwide [1, 2]. Outbreaks of LPAI viruses belonging to H7 and H9 subtypes in chickens have been reported in the past [3,4,5,6] and infections caused by H7N9 and H9N2 LPAI viruses have infected poultry birds and demonstrated their potential to infect humans [7, 8]. Despite being primarily a poultry pathogen, the H9N2 virus has been reported to diversify the host range and conferring a zoonotic transmission potential to H7N9 and H10N8 viruses, which are reported to cause deadly human infections [6, 11, 12]. Subunit-based vaccines that are easy to manipulate, produce, and scale-up and targeting conserved epitopes that are known to stimulate a broad spectrum of protection would be the ideal choice for controlling outbreaks caused by emergent pandemic strains
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