Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV

Development of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns whe...

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Autores principales:	Dongliang Liu, Sheng Zhang, Ethan Poteet, Christian Marin-Muller, Changyi Chen, Qizhi Yao
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HIV virus-like particles vaccine mucosal immunization immune response IgA Medicine R
Acceso en línea:	https://doaj.org/article/6c21dd1fa9064b90bb44df71145dae7d
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spelling	oai:doaj.org-article:6c21dd1fa9064b90bb44df71145dae7d2021-11-25T19:10:21ZSublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV10.3390/vaccines91112362076-393Xhttps://doaj.org/article/6c21dd1fa9064b90bb44df71145dae7d2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1236https://doaj.org/toc/2076-393XDevelopment of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns when administered intranasally. Sublingual immunization has received more attention in recent years based on its efficiency in inducing systemic and mucosal immune responses in both mucosal and extra-mucosal tissues. To facilitate the transport of the immunogen across the sub-mucosal epithelial barrier, we found that CD91, the receptor of C1q, is prevalently expressed in the sublingual mucosal lining, and thus, a modified chimeric C1q surface conjugated CD40L/HIV VLP was generated. The ability of this chimeric C1q/CD40L/HIV VLP to bind, cross the epithelial layer, access and activate the sub-mucosal layer dendritic cells (DCs), and ultimately induce enhanced mucosal and systemic immune responses against HIV is evaluated in this study. We found that C1q/CD40L/HIV VLPs have enhanced binding, increased transport across the epithelial layer, and upregulate DC activation markers as compared to CD40L/HIV VLPs alone. Mice immunized with C1q/CD40L/HIV VLPs by sublingual administration showed higher levels of IgA salivary antibodies against both HIV Gag and Env than mice immunized with CD40L/HIV VLPs. Moreover, sublingual immunization with C1q/CD40L/HIV VLPs induced more Env- and Gag-specific IFN-γ producing T cells than the CD40L/HIV VLPs group. Interestingly, C1q/CD40L/HIV VLP immunization can also induce more mucosal homing T cells than that in CD40L/HIV VLP group. Our data suggest that incorporation of C1q to CD40L/HIV VLPs is a promising novel strategy and that the sublingual immunization can be a favorite immunization route for HIV mucosal vaccines.Dongliang LiuSheng ZhangEthan PoteetChristian Marin-MullerChangyi ChenQizhi YaoMDPI AGarticleHIVvirus-like particlesvaccinemucosal immunizationimmune responseIgAMedicineRENVaccines, Vol 9, Iss 1236, p 1236 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV virus-like particles vaccine mucosal immunization immune response IgA Medicine R
spellingShingle	HIV virus-like particles vaccine mucosal immunization immune response IgA Medicine R Dongliang Liu Sheng Zhang Ethan Poteet Christian Marin-Muller Changyi Chen Qizhi Yao Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
description	Development of a vaccine that can elicit robust HIV specific antibody responses in the mucosal compartments is desired for effective prevention of HIV via sexual transmission. However, the current mucosal vaccines have either poor immunogenicity when administered orally or invite safety concerns when administered intranasally. Sublingual immunization has received more attention in recent years based on its efficiency in inducing systemic and mucosal immune responses in both mucosal and extra-mucosal tissues. To facilitate the transport of the immunogen across the sub-mucosal epithelial barrier, we found that CD91, the receptor of C1q, is prevalently expressed in the sublingual mucosal lining, and thus, a modified chimeric C1q surface conjugated CD40L/HIV VLP was generated. The ability of this chimeric C1q/CD40L/HIV VLP to bind, cross the epithelial layer, access and activate the sub-mucosal layer dendritic cells (DCs), and ultimately induce enhanced mucosal and systemic immune responses against HIV is evaluated in this study. We found that C1q/CD40L/HIV VLPs have enhanced binding, increased transport across the epithelial layer, and upregulate DC activation markers as compared to CD40L/HIV VLPs alone. Mice immunized with C1q/CD40L/HIV VLPs by sublingual administration showed higher levels of IgA salivary antibodies against both HIV Gag and Env than mice immunized with CD40L/HIV VLPs. Moreover, sublingual immunization with C1q/CD40L/HIV VLPs induced more Env- and Gag-specific IFN-γ producing T cells than the CD40L/HIV VLPs group. Interestingly, C1q/CD40L/HIV VLP immunization can also induce more mucosal homing T cells than that in CD40L/HIV VLP group. Our data suggest that incorporation of C1q to CD40L/HIV VLPs is a promising novel strategy and that the sublingual immunization can be a favorite immunization route for HIV mucosal vaccines.
format	article
author	Dongliang Liu Sheng Zhang Ethan Poteet Christian Marin-Muller Changyi Chen Qizhi Yao
author_facet	Dongliang Liu Sheng Zhang Ethan Poteet Christian Marin-Muller Changyi Chen Qizhi Yao
author_sort	Dongliang Liu
title	Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
title_short	Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
title_full	Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
title_fullStr	Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
title_full_unstemmed	Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV
title_sort	sublingual immunization with chimeric c1q/cd40 ligand/hiv virus-like particles induces strong mucosal immune responses against hiv
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6c21dd1fa9064b90bb44df71145dae7d
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Sublingual Immunization with Chimeric C1q/CD40 Ligand/HIV Virus-like Particles Induces Strong Mucosal Immune Responses against HIV

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