tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2022 Nov 11;20(1):477.
doi: 10.1186/s12951-022-01677-2.
A split influenza vaccine formulated with a combination adjuvant composed of alpha-D-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs
V Patil[SUP] 1 [/SUP], J F Hernandez-Franco[SUP] 2 [/SUP], G Yadagiri[SUP] 1 [/SUP], D Bugybayeva[SUP] 1 3 [/SUP], S Dolatyabi[SUP] 1 [/SUP], N Feliciano-Ruiz[SUP] 1 [/SUP], J Schrock[SUP] 1 [/SUP], J Hanson[SUP] 1 [/SUP], J Ngunjiri[SUP] 1 [/SUP], H HogenEsch[SUP] 4 [/SUP], G J Renukaradhya[SUP] 5 [/SUP]
Affiliations
Abstract
Background: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus.
Results: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10[SUP]+[/SUP] myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ[SUP]+[/SUP] effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A[SUP]+[/SUP] T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ[SUP]+[/SUP] late effector CTLs and effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total CTLs, late effector CTLs, and CXCL10[SUP]+[/SUP] myeloid cells in blood, as well as lung CXCL10[SUP]+[/SUP] plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs.
Conclusions: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.
Keywords: ADU-S100; Cellular immunity; Nano-11; Pigs; Swine influenza A viruses; Vaccination.
. 2022 Nov 11;20(1):477.
doi: 10.1186/s12951-022-01677-2.
A split influenza vaccine formulated with a combination adjuvant composed of alpha-D-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs
V Patil[SUP] 1 [/SUP], J F Hernandez-Franco[SUP] 2 [/SUP], G Yadagiri[SUP] 1 [/SUP], D Bugybayeva[SUP] 1 3 [/SUP], S Dolatyabi[SUP] 1 [/SUP], N Feliciano-Ruiz[SUP] 1 [/SUP], J Schrock[SUP] 1 [/SUP], J Hanson[SUP] 1 [/SUP], J Ngunjiri[SUP] 1 [/SUP], H HogenEsch[SUP] 4 [/SUP], G J Renukaradhya[SUP] 5 [/SUP]
Affiliations
- PMID: 36369044
- DOI: 10.1186/s12951-022-01677-2
Abstract
Background: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus.
Results: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10[SUP]+[/SUP] myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ[SUP]+[/SUP] effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A[SUP]+[/SUP] T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ[SUP]+[/SUP] late effector CTLs and effector memory T-helper/memory cells, IL-17A[SUP]+[/SUP] total CTLs, late effector CTLs, and CXCL10[SUP]+[/SUP] myeloid cells in blood, as well as lung CXCL10[SUP]+[/SUP] plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs.
Conclusions: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.
Keywords: ADU-S100; Cellular immunity; Nano-11; Pigs; Swine influenza A viruses; Vaccination.