Titrating T‐Cell Epitopes within Self‐Assembled Vaccines Optimizes CD4+ Helper T Cell and Antibody Outputs

Pompano, Rebecca R.; Chen, Jianjun; Verbus, Emily; Han, Hua; Fridman, Arthur; McNeely, Tessie; Collier, Joel H.; Chong, Anita S.

doi:10.1002/adhm.201400137

Cited by 119 publications

(151 citation statements)

References 62 publications

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“…The immune response was also shown to be tunable in an experiment where a fiber was formed by co-assembly of a B cell (E214-Q11) and T cell (PADRE-Q11) epitope [126]. By varying the concentrations of each B and T cell epitope, the optimal T helper cell and antibody responses were selected.…”

Section: Peptide-peptide Interaction Driven Self-assemblymentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

203

155

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Peptides and peptide-conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self-assembled nanostructures based on peptides and peptide-conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self-assembly of various nanomaterials based on peptides and peptide-conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self-assembly. First, we present the self-assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. The studies where nanoassembly is driven by the interactions between the conjugates of peptide-conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine, and challenges and future perspective are presented.

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Section: Peptide-peptide Interaction Driven Self-assemblymentioning

confidence: 99%

Self-assembling peptide-based building blocks in medical applications

Acar

Srivastava

Chung

et al. 2017

Advanced Drug Delivery Reviews

203

155

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“…Here we report on the thermal stability characteristics of self-assembled peptide nanofiber vaccines, which are both self-adjuvanting and constructed from short, unfolded peptide epitopes. Short peptides containing fibrillizing domains such as Q11 (QQKFQFQFEQQ) [13–18] or KFE8 (FKFEFKFE) [17] can be appended with T or B cell epitopes; when they are mixed with physiologic buffers, media, or fluids, they self-assemble into nanofibers displaying the epitopes, and we have found that these nanofibers raise strong immune responses without supplemental adjuvants [13,15–17]. The modularity of the platform makes it simple to adjust the epitope content within the nanofibers, and we have observed phenotypic modulation of T cell subsets when the T and B cell epitope ratios are varied [15].…”

Section: Introductionmentioning

confidence: 99%

“…Both epitopes are able to raise B cell and T cell responses [13, 19]. Having both a B cell epitope and a T cell epitope is essential for Q11-based vaccines, as Q11 nanofibers lacking either do not raise strong antibody responses [15,17]. We investigated the thermostability of lyophilized peptides as well as aqueous suspensions of nanofibers, finding that some formulations were more thermostable than others, with the most thermostable (ESAT-Q11) being capable of withstanding elevated temperatures of 45°C for as long as six months without diminishment of effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Thermal stability of self-assembled peptide vaccine materials

et al. 2016

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The majority of current vaccines depend on a continuous “cold chain” of storage and handling between 2–8°C. Vaccines experiencing temperature excursions outside this range can suffer from reduced potency. This thermal sensitivity results in significant losses of vaccine material each year and risks the administration of vaccines with diminished protective ability, issues that are heightened in the developing world. Here, using peptide self-assemblies based on the fibril-forming peptide Q11 and containing the epitopes OVA323-339 from ovalbumin or ESAT651-70 from Mycobacterium tuberculosis, the chemical, conformational, and immunological stability of supramolecular peptide materials were investigated. It was expected that these materials would exhibit advantageous thermal stability owing to their adjuvant-free and fully synthetic construction. Neither chemical nor conformational changes were observed for either peptide when stored at 45°C for 7 days. ESAT651-70-Q11 was strongly immunogenic whether it was stored as a dry powder or as aqueous nanofibers, showing undiminished immunogenicity even when stored as long as six months at 45°C. This result was in contrast to ESAT651-70 conjugated to a protein carrier and adjuvanted with alum, which demonstrated marked thermal sensitivity in these conditions. Antibody titers and affinities were undiminished in mice for OVA323-339-Q11 if it was stored as assembled nanofibers, yet some diminishment was observed for material stored as a dry powder. The OVA study was done in a different mouse strain and with a different prime/boost regimen, and so it should not be compared directly with the study for the ESAT epitope. This work indicates that peptide self-assemblies can possess attractive thermal stability properties in the context of vaccine development.

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“…Low dose influenza peptides favour a Th1 response, and at very high concentrations favour Th2/T follicular helper (T FH ) cell response (Brown et al, 2009; Pompano et al, 2014). The relationship between T FH and antigen dose corresponds to a recent study founding a greater frequency of (peripheral) pT FH post-vaccination in those receiving HD compared to SD vaccine (Pilkinton et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

Merani

Kuchel

Kleppinger³

et al. 2018

Experimental Gerontology

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Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥ 65 years) were enrolled (n = 106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20 weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.

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Titrating T‐Cell Epitopes within Self‐Assembled Vaccines Optimizes CD4+ Helper T Cell and Antibody Outputs

Cited by 119 publications

References 62 publications

Self-assembling peptide-based building blocks in medical applications

Self-assembling peptide-based building blocks in medical applications

Thermal stability of self-assembled peptide vaccine materials

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

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