Comparison of Fluorinated and Nonfluorinated Lipids in Self-Adjuvanting Delivery Systems for Peptide-Based Vaccines

Hussein, Waleed M.; Mukaida, Saori; Azmi, Fazren; Bartlett, Stacey; Olivier, C.; Batzloff, Michael R.; Good, Michael F.; Skwarczynski, Mariusz; Tóth, István

doi:10.1021/acsmedchemlett.6b00453

Cited by 12 publications

(12 citation statements)

References 28 publications

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“…HPV-16 E7 44-57 and E6 43-57 CTL epitopes were conjugated to fluorinated lipids and self-assembled into spherical particles (10–15 nm). 149 , 150 However, the fluorinated lipopeptides were unable to activate a strong CTL response against tumors. 149…”

Section: Adjuvants and Delivery Systems In Peptide-based Hpv Therapeu...mentioning

confidence: 99%

Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances

Zhang¹,

Fan²,

Skwarczynski³

et al. 2022

IJN

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Persistent infection with high-risk human papillomaviruses (HPVs), such as HPV-16 and HPV-18, can induce cervical cancer in humans. The disease carries high morbidity and mortality among females worldwide. Inoculation with prophylactic HPV vaccines, such as Gardasil ® or Cervarix ® , is the predominant method of preventing cervical cancer in females 6 to 26 years of age. However, despite the availability of commercial prophylactic HPV vaccines, no therapeutic HPV vaccines to eliminate existing HPV infections have been approved. Peptide-based vaccines, which form one of the most potent vaccine platforms, have been broadly investigated to overcome this shortcoming. Peptide-based vaccines are especially effective in inducing cellular immune responses and eradicating tumor cells when combined with nanoscale adjuvant particles and delivery systems. This review summarizes progress in the development of peptide-based nanovaccines against HPV infection.

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Section: Adjuvants and Delivery Systems In Peptide-based Hpv Therapeu...mentioning

confidence: 99%

Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances

Zhang¹,

Fan²,

Skwarczynski³

et al. 2022

IJN

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“…Figure 2A illustrates that only SLS-N PNC induced a significant increase in co-expression of MHC I presenting SIINFEKL and CD86 in lymph node DCs. Nanoparticles have been shown to have "self-adjuvanting" properties due to their nanoparticulate nature (54)(55)(56). This benefit of PNC may explain the increased maturation specifically of SIINFEKL-presenting DCs in mice administered PNC compared to soluble groups, which displayed low levels of maturation.…”

Section: Dendritic Cell Processingmentioning

confidence: 99%

Rational Design of Antigen Incorporation Into Subunit Vaccine Biomaterials Can Enhance Antigen-Specific Immune Responses

Tsoras¹,

Wong²,

Paravastu³

et al. 2020

Front. Immunol.

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“…Particle-based carrier systems can act as adjuvants while also serving as a protective delivery system that enhances recognition and internalization by phagocytic antigen presenting cells (APCs) . Carrier materials like lipids, polymers, , gas vesicle nanoparticles (GVNPs), virus-like particles (VLPs), and metal organic frameworks have been used to stabilize, modulate delivery, and increase immunogenicity of peptide antigens. Conjugation of antigen to nanoparticulates, membrane proteins, universal T cell epitopes, , or other materials with DC targeting capabilities such as CpG oligodeoxynucleotides, heat shock proteins, or DC-targeting peptide (DCpep) have also been shown to improve protective immune responses and decrease side effects by inducing trafficking to lymph nodes or targeting specific immune cell receptors.…”

Section: Introductionmentioning

confidence: 99%

Cross-Linked Peptide Nanoclusters for Delivery of Oncofetal Antigen as a Cancer Vaccine

Tsoras

Champion

2018

Bioconjugate Chem.

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Peptide subunit vaccines are desirable because they increase control over the immune response and safety of the vaccine by reducing the risk of off-target responses to molecules other than the target antigen. The immunogenicity of most peptides, however, is low. Peptide nanoclusters (PNC) are proposed as a subunit peptide vaccine delivery system made completely of cross-linked peptide antigen that could improve the immunogenicity of a peptide vaccine. Proof of concept is demonstrated with oncofetal antigen (OFA), an immature laminin receptor protein expressed by many hematologic cancer cells but not by healthy cells. Peptide epitopes from this protein, called OFA 1, 2, and 3, were synthesized into PNC as a potential cancer peptide vaccine delivery system. PNC were formed by desolvation and stabilized with disulfide bonds using a trithiol cross-linker. Cysteines were added to the C-terminus of each peptide to assist in this cross-linking step, denoted OFA 1C, 2C, and 3C PNC. OFA 2C was found to form the smallest PNC, 148 ± 15 nm in diameter and stable in solution. This size is in the range where particles are readily internalized by dendritic cells (DCs) and may also passively diffuse to regional lymph nodes. OFA 2C PNC and soluble OFA 2C were internalized similarly by DCs in vitro, but only PNC resulted in significant peptide presentation by DCs. This indicates the potential for PNC to improve immune activation against this antigen. Additionally, PNC displayed higher retention at the intradermal injection site in vivo than soluble peptide, allowing more time to interact with DCs in an area of increased DC activity. While offering traditional nanoparticle benefits such as increased DC recognition, slower diffusion, and potential for multivalent cellular interactions, PNC also maximize antigen delivered per particle while minimizing off-target material delivery because the antigens are the main building blocks of the particle. With these properties, PNC are a delivery system with potential to increase peptide subunit vaccine immunogenicity for OFA and other peptide antigens.

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Comparison of Fluorinated and Nonfluorinated Lipids in Self-Adjuvanting Delivery Systems for Peptide-Based Vaccines

Cited by 12 publications

References 28 publications

Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances

Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances

Rational Design of Antigen Incorporation Into Subunit Vaccine Biomaterials Can Enhance Antigen-Specific Immune Responses

Cross-Linked Peptide Nanoclusters for Delivery of Oncofetal Antigen as a Cancer Vaccine

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