Subunit-based vaccines

Ausar, Salvador F.; Larson, Nicholas R.; Wei, Yangjie; Jain, Akshay; Middaugh, C. Russell

doi:10.1016/b978-0-12-814357-5.00001-5

Cited by 3 publications

(4 citation statements)

References 172 publications

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“…In consequence, the protein-based vaccines often fail in mounting effective immune responses from pathogens (e.g. viruses) that proliferate intracellularly [1]. Traditional vaccines also have major limitations including low stability, necessity of 'cold chain' storage, transport, high price and time-consuming production.…”

Section: Introductionmentioning

confidence: 99%

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Rahaman,

Chaudhuri

2023

Biomed. Mater.

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To ensure effective immune response in genetic immunizations, DNA/mRNA vaccines need to be delivered to body’s antigen presenting cells (APCs) which is a challenging task. This is primarily due to presence of high concentrations of various degradative enzymes inside them. To this end, mannose receptor (over expressed in APCs) selective cationic liposomes have been used in the past for delivering antigen-encoded plasmid DNA to APCs. APCs also express integrin receptors on their cell surfaces. However, studies aimed at delivering DNA vaccines into APCs via integrin receptors have not yet been undertaken. Herein, we report on the use of cationic liposomes of a priorly disclosed α5β1 integrin receptor selective RGDK-lipopeptide for macrophage transfection. In this study, we have used pCMV-GFP (as model DNA vaccine) and RAW 264.7 cells (mouse macrophages cells) as model APC. We show that the liposomes of RGDK-lipopeptide containing a previously reported endosome-disrupting histidinylated lipid and DOPE (as co-lipid) in 0.5:0.5:1.0 mole ratio are the most competent in transfecting macrophage cells (44%). Findings in the fluorescence resonance energy transfer based membrane fusogencity assay revealed that the enhanced macrophage transfection efficiency of the liposomes containing RGDK-lipopeptide, endosome-disrupting histidinylated and DOPE may originate from its higher membrane fusogenicity than that for liposomes containing only RGDK-lipopeptide and DOPE. The presently described biologically safe liposomal formulations of RGDK-lipopeptide are expected to find biomedical applications in future for combating cancer and infectious diseases through genetic immunizations.

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Section: Introductionmentioning

confidence: 99%

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Rahaman,

Chaudhuri

2023

Biomed. Mater.

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“…[20][21][22][23][24] In modern immunization strategies, the selection of antigenic peptide epitopes from a given pathogen's protein repertoire is often key to developing successful antibody and T cell responses against infectious pathogens. However, vaccination with such peptides alone usually fails to promote sufficiently robust responses, [25][26] requiring the use of carrier proteins for conjugate vaccines, a role for which protein nanoparticles are well suited by virtue of their efficient lymphatic trafficking, engagement of immune cell receptors, uptake, processing, and induction of cellular signaling. 25,[27][28][29] While encapsulin particles have several beneficial attributes, including high stability, versatile tolerance of sequence modification, and excellent expression yields, they have only occasionally been employed as immunogenic carrier proteins, as follows.…”

Section: Introductionmentioning

confidence: 99%

“…In modern immunization strategies, the selection of antigenic peptide epitopes from a given pathogen’s protein repertoire is often key to developing successful antibody and T cell responses against infectious pathogens. However, vaccination with such peptides alone usually fails to promote sufficiently robust responses, 25–26 requiring the use of carrier proteins for conjugate vaccines, a role for which protein nanoparticles are well suited by virtue of their efficient lymphatic trafficking, engagement of immune cell receptors, uptake, processing, and induction of cellular signaling. 25, 27–29…”

Section: Introductionmentioning

confidence: 99%

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

Bhattacharya,

Jenkins,

Keshavarz-Joud

et al. 2024

Preprint

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Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins fromMxyococcus xanthuswere designed to package bacterial RNA when produced inE. coliand were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle. This immunogen elicited conformationally-relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.Table of Contents graphic

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“…In modern immunization strategies, the selection of antigenic peptide epitopes from a given pathogen’s protein repertoire is often key to developing successful antibody and T cell responses against infectious pathogens. However, vaccination with such peptides alone usually fails to promote sufficiently robust responses, , requiring the use of carrier proteins for conjugate vaccines, a role for which protein nanoparticles are well suited by virtue of their efficient lymphatic trafficking, engagement of immune cell receptors, uptake, processing, and induction of cellular signaling. ,− …”

Section: Introductionmentioning

confidence: 99%

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

Bhattacharya,

Jenkins,

Keshavarz-Joud

et al. 2024

ACS Nano

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Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Myxococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle, inducing the formation of several nonicosahedral structures that were characterized by cryogenic electron microscopy. This immunogen elicited conformationally relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.

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Subunit-based vaccines

Cited by 3 publications

References 172 publications

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

RGDK-lipopeptide for targeting genetic vaccines to antigen presenting cells

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

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