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Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides.

ABSTRACT: An HIV vaccine capable of inducing high and durable levels of broadly neutralizing antibodies has thus far proven elusive. A promising antigen is the membrane-proximal external region (MPER) from gp41, a segment of the viral envelope recognized by a number of broadly neutralizing antibodies. Though an attractive vaccine target due to the linear nature of the epitope and its highly conserved sequence, MPER peptides are poorly immunogenic and may require display on membranes to achieve a physiological conformation matching the native virus. Here we systematically explored how the structure and composition of liposomes displaying MPER peptides impacts the strength and durability of humoral responses to this antigen as well as helper T-cell responses in mice. Administration of MPER peptides anchored to the surface of liposomes induced MPER-specific antibodies whereas MPER administered in oil-based emulsion adjuvants or alum did not, even when combined with Toll-like receptor agonists. High-titer IgG responses to liposomal MPER required the inclusion of molecular adjuvants such as monophosphoryl lipid A. Anti-MPER humoral responses were further enhanced by incorporating high-Tm lipids in the vesicle bilayer and optimizing the MPER density to a mean distance of ?10-15 nm between peptides on the liposomes' surfaces. Encapsulation of helper epitopes within the vesicles allowed efficient "intrastructural" T-cell help, which promoted IgG responses to MPER while minimizing competing B-cell responses against the helper sequence. These results define several key properties of liposome formulations that promote durable, high-titer antibody responses against MPER peptides, which will be a prerequisite for a successful MPER-targeting vaccine.

SUBMITTER: Hanson MC

PROVIDER: S-EPMC4312707 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides.

Hanson Melissa C MC Abraham Wuhbet W Crespo Monica P MP Chen Stephanie H SH Liu Haipeng H Szeto Greg Lee GL Kim Mikyung M Reinherz Ellis L EL Irvine Darrell J DJ

Vaccine 20150102 7

An HIV vaccine capable of inducing high and durable levels of broadly neutralizing antibodies has thus far proven elusive. A promising antigen is the membrane-proximal external region (MPER) from gp41, a segment of the viral envelope recognized by a number of broadly neutralizing antibodies. Though an attractive vaccine target due to the linear nature of the epitope and its highly conserved sequence, MPER peptides are poorly immunogenic and may require display on membranes to achieve a physiolog ...[more]

PMID: 25559188

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Project description:Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths. To improve vaccine equity, vaccine design must take into consideration the logistics needed to implement a successful vaccination drive, particularly among the most vulnerable populations. In the manuscript titled "Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette-Guérin Vaccination to Improve Antiviral Antibody Responses" published in the Journal of Immunology, the authors designed a recombinant subunit vaccine against the Ebola virus (EBOV) glycoprotein that can harness the pre-existing T helper cells from prior BCG vaccination. As a recombinant subunit vaccine adjuvanted with alum, this approach has many features that make it well suited for the design of vaccines for developing nations, such as relative ease of production, scalability, and distribution. In addition, the high prevalence of BCG immunization and natural immunity to mycobacteria in many regions of the world endow such vaccines with features that should increase potency and efficacy among populations residing in such regions. As a result of using the helper activity of pre-existing BCG-specific Th cells to drive antibody responses, a lower vaccine dose is needed, which is a major advantage for vaccine manufacture. Furthermore, the BCG-specific Th cells also stimulate immunoglobulin class switching to IgG isotypes that have strong affinities for activating Fc-gamma receptors (FcγRs). Taken together, we propose that the design of subunit vaccines with intrastructural help from BCG-specific Th cells can improve protection against viral infection and represents a vaccine design that can be generally adapted to other emerging viral pathogens for the control and prevention of infection in many developing countries.

Dataset Information

Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides.

Publications

Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides.

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