title: Modular virus-like particles for sublingual vaccination against group A streptococcus.
abstract: Infection with Group A streptococcus (GAS)-an oropharyngeal pathogen-leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity. By using in vivo tracing of the sublingual J8-VLPs, we visualized the draining of J8-VLPs into the submandibular lymph nodes, in parallel with its rapid absorption into the systemic circulation, which support the induction of effective immune responses in both systemic and mucosal compartments. The sublingual administration of J8-VLPs resulted in a high serum IgG antibody level, with a good balance of Th1 and Th2 immune responses. Of note, sublingual vaccination with J8-VLPs elicited high levels of IgA antibody in the saliva. The co-administration of mucosal adjuvant cholera toxin (CT) further enhanced the increase in salivary IgA antibody levels induced by the J8-VLPs formulation. Moreover, the levels of salivary IgA and serum IgG observed following the administration of the CT-adjuvanted FD formulation of J8-VLPs (FD-J8-VLPs) and non-FD formulation of J8-VLPs were comparable. In fact, the saliva isolated from mice immunized with J8-VLPs and FD-J8-VLPs with CT demonstrated opsonizing activity against GAS in vitro. Thus, we observed that the sublingually delivered FD formulation of microbially produced modular VLPs could prevent and control GAS diseases in endemic areas in a cost-effective manner.
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Arjun
authors.initials: A
authors.lastname: Seth
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Il Gyu
authors.initials: IG
authors.lastname: Kong
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yeji
authors.initials: Y
authors.lastname: Kim
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Nani
authors.initials: N
authors.lastname: Wibowo
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD 4072, Australia.
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
authors.affiliation: The University of Queensland, Protein Expression Facility, St Lucia, QLD 4072, Australia. Electronic address: l.lua@uq.edu.au.
authors.forename: Linda H L
authors.initials: LH
authors.lastname: Lua
authors.affiliation: Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Republic of Korea. Electronic address: mnkweon@amc.seoul.kr.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000286:Administration, Sublingual; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000032:analysis; D012463:Saliva / Q000276:immunology; D044967:Serum / Q000276:immunology; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D022541:Streptococcal Vaccines; D058425:Vaccines, Virus-Like Particle; D002772:Cholera Toxin
keywords: Freeze drying; Group A streptococcus; In vivo imaging; Mucosal vaccine; Sublingual administration; Vaccine; Virus-like particles