Modular virus-like particles for sublingual vaccination against group A streptococcus. Issue 51 (12th December 2016)

• Record Type: Journal Article
• Authors: Seth, Arjun; Kong, Il Gyu; Lee, Su-Hyun; Yang, Jin-Young; Lee, Yong-Soo; Kim, Yeji; Wibowo, Nani; Middelberg, Anton P.J.; Lua, Linda H.L.; Kweon, Mi-Na
• Is Part Of: Vaccine. Volume 34:Issue 51(2016)
• Page Start: 6472
• Page End: 6480
• Publication Date: 2016-12-12
• Subjects: CFU colony-forming units -- CT cholera toxin -- DLS dynamic light scattering -- FD freeze dried -- GAS group A streptococcus -- MALS multi-angle light scattering -- MPyV murine polyomavirus -- TEM transmission electron microscopy -- TLC thin layer chromatography -- VLPs virus-like particles -- WT wild-type; Group A streptococcus -- Vaccine -- Mucosal vaccine -- Sublingual administration -- Virus-like particles -- In vivo imaging -- Freeze drying; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.11.008
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Sublingual vaccination with modular VLPs elicited systemic and mucosal antibodies. Cholera toxin enhanced IgA level induced by sublingually vaccinated modular VLPs. Freeze-dried modular VLPs induced high levels of J8i-specific IgG antibody. Adjuvanted freeze-dried modular VLPs generated opsonization antibodies. 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.