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

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.

Nanoparticle Technology for Respiratory Tract Mucosal Vaccine Delivery

“…PLGA nanoparticles have been explored as carriers in a multitude of examples, including for oral and pulmonary vaccination against hepatitis B (Gupta P.N. et al, 2007;Mishra N. et al, 2011;Thomas C. et al, 2011), ocular and nasal delivery of influenza antigens (Alkie T.N. et al, 2018), and microparticles for pulmonary vaccination against tuberculosis .…”

Evaluation in broilers of aerosolized nanoparticles vaccine encapsulating imuno-stimulant and antigens of avian influenza virus/Mycoplasma gallisepticum

“…There was a significantly higher mean H9N2 specific-IgA in birds of TRTs 3 and 5 that received the EEsupplemented vaccine, compared to that in birds of TRT 1 that were deprived of this supplementation (P<0.05). The boosting by the aerosolized vaccine at 21…”

“…The lowest recovery of tracheal MG and H9N2 from challenged birds was in those allocated to TRT 3 (Table 4), who had the appropriate priming that led to the highest MG and H9N2 -specific IgA and IgG in their tracheobronchial washings at the challenge age of 28 d (Table 3). Previous reports documented the role of IgA and IgG in local protection against tracheal infection of broilers by the two organisms [21,22,50,51,52], emphasizing the role of mucosal immunity in projects targeting the control of these two pathogens in poultry.…”

“…Scientists are currently searching for alternatives to the costly injectable killed vaccines, and to the injurious approach of administering live vaccine strains of H9N2 and MG in poultry. Preliminary attempts in deliverance of soluble antigens through the nasal passage, for immunization against AI [21,22] and MG [23], are documented. Such attempts led to sporadic acquirement of immune responses [21][22][23], with a need to augment the induction of local immunity in the respiratory tract, and to establish a relationship between this augmentation and protection against coinfection by MG and H9N2.…”

“…The search for immuno-stimulants targeting the epithelial layer of the respiratory system in poultry and its impact on protection against avian influenza alone or in coinfection with MG, are not given enough attention during the last decades [31][32][33][34][35]. The first work on evaluation of liposomal vaccines in poultry, administered via the subcutaneous route, and constructed of cationic micelles, is documented in the year 1987 [36].…”