Characterization of immunogenicity of avian influenza antigens encapsulated in PLGA nanoparticles following mucosal and subcutaneous delivery in chickens.

Tamiru Negash Alkie,Shayan Sharif,Jake Astill,Khaled Taha-Abdelaziz,Alexander Yitbarek,Paulo Lee Ho

doi:10.1371/journal.pone.0206324

Tamiru Negash Alkie, Shayan Sharif + Show 4 more

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https://doi.org/10.1371/journal.pone.0206324

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Abstract

Mucosal vaccine delivery systems have paramount importance for the induction of mucosal antibody responses. Two studies were conducted to evaluate immunogenicity of inactivated AIV antigens encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). In the first study, seven groups of specific pathogen free (SPF) layer-type chickens were immunized subcutaneously at 7-days of age with different vaccine formulations followed by booster vaccinations two weeks later. Immune responses were profiled by measuring antibody (Ab) responses in sera and lachrymal secretions of vaccinated chickens. The results indicated that inactivated AIV and CpG ODN co-encapsulated in PLGA NPs (2x NanoAI+CpG) produced higher amounts of hemagglutination inhibiting antibodies compared to a group vaccinated with non-adjuvanted AIV encapsulated in PLGA NPs (NanoAI). The tested adjuvanted NPs-based vaccine (2x NanoAI+CpG) resulted in higher IgG responses in the sera and lachrymal secretions at weeks 3, 4 and 5 post-vaccination when immunized subcutaneously. The incorporation of CpG ODN led to an increase in Ab-mediated responses and was found useful to be included both in the prime and booster vaccinations. In the second study, the ability of chitosan and mannan coated PLGA NPs that encapsulated AIV and CpG ODN was evaluated for inducing antibody responses when delivered via nasal and ocular routes in one-week-old SPF layer-type chickens. These PLGA NPs-based and surface modified formulations induced robust AIV-specific antibody responses in sera and lachrymal secretions. Chitosan coated PLGA NPs resulted in the production of large quantities of lachrymal IgA and IgG compared to mannan coated NPs, which also induced detectable amounts of IgA in addition to the induction of IgG in lachrymal secretions. In both mucosal and subcutaneous vaccination approaches, although NPs delivery enhanced Ab-mediated immunity, one booster vaccination was required to generate significant amount of Abs. These results highlight the potential of NPs-based AIV antigens for promoting the induction of both systemic and mucosal immune responses against respiratory pathogens.

Highlights

Avian influenza viruses (AIV) are classified into low pathogenic and highly pathogenic viruses
The results revealed that the inclusion of CpG ODN in the vaccine formulation, 2x NanoAI+CpG and NanoAI+CpG/ NanoAI induced higher serum IgM (OD-values of 1.8 and 1.4, respectively) at week 3 post-primary vaccination compared to formulations lacking CpG ODN such as 2x NanoAI or a group primed with NanoAI and boosted with NanoAI+CpG (NanoAI/NanoAI+CpG) (Fig 2B) (p
Chitosan and mannan coated PLGA NPs induced higher lachrymal IgG and IgA as well as serum antibody when delivered in a prime-boost strategy by the ocular and nasal routes

Summary

Introduction

Avian influenza viruses (AIV) are classified into low pathogenic and highly pathogenic viruses. The systemic immunity induced by these vaccines provide partial to complete protection from disease progression, but generally does not prevent infection and virus shedding from infected birds [6,7]. This indicates the need to improve the immunogenicity and efficacy of existing AIV vaccines, which can be achieved by selecting adjuvants with superior ability to induce innate and adaptive immune responses [8,9], by exploring appropriate routes of vaccination [10] and by optimizing vaccine delivery methods [11,12,13]

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