Modular virus-like particles for sublingual vaccination against group A streptococcus

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. and Kweon, Mi-Na (2016) Modular virus-like particles for sublingual vaccination against group A streptococcus. Vaccine, 34 51: 6472-6480. doi:10.1016/j.vaccine.2016.11.008


Author 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
Title Modular virus-like particles for sublingual vaccination against group A streptococcus
Journal name Vaccine   Check publisher's open access policy
ISSN 0264-410X
1873-2518
Publication date 2016-12-12
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.vaccine.2016.11.008
Open Access Status Not yet assessed
Volume 34
Issue 51
Start page 6472
End page 6480
Total pages 9
Place of publication London, United Kingdom
Publisher Elsevier
Language eng
Subject 1313 Molecular Medicine
2400 Immunology and Microbiology
3400 Veterinary
2739 Public Health, Environmental and Occupational Health
2725 Infectious Diseases
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.
Formatted 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.
Keyword Group A streptococcus
Vaccine
Mucosal vaccine
Sublingual administration
Virus-like particles
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HI13C0016
2016-678
NRF-2016R1C1B1014775
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
 
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Created: Wed, 30 Nov 2016, 22:43:10 EST by Linda Lua on behalf of Aust Institute for Bioengineering & Nanotechnology