Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines

Mehta, Naveen K.; Pradhan, Roma V.; Soleimany, Ava P.; Moynihan, Kelly D.; Rothschilds, Adrienne M.; Momin, Noor; Rakhra, Kavya; Mata-Fink, Jordi; Bhatia, Sangeeta N.; Wittrup, K. Dane; Irvine, Darrell J.

doi:10.1038/s41551-020-0563-4

Cited by 48 publications

(40 citation statements)

References 64 publications

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“…Albumin-binding dyes target draining lymph nodes and thus provide a strategy for the visual identification of sentinel lymph nodes following intratumoural administration 183 . Molecular vaccine cargo can also be designed to ‘hitch-hike’ albumin for the passive targeting of lymph node-resident APCs 173 , 184 . This hitch-hiking strategy increases the magnitude of T cell activation by >30-fold, compared with standard bolus administration of the antigen alone 173 , 184 .…”

Section: Designing Spatial and Temporal Controlmentioning

confidence: 99%

Designing spatial and temporal control of vaccine responses

et al. 2021

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Vaccines are the key technology to combat existing and emerging infectious diseases. However, increasing the potency, quality and durability of the vaccine response remains a challenge. As our knowledge of the immune system deepens, it becomes clear that vaccine components must be in the right place at the right time to orchestrate a potent and durable response. Material platforms, such as nanoparticles, hydrogels and microneedles, can be engineered to spatially and temporally control the interactions of vaccine components with immune cells. Materials-based vaccination strategies can augment the immune response by improving innate immune cell activation, creating local inflammatory niches, targeting lymph node delivery and controlling the time frame of vaccine delivery, with the goal of inducing enhanced memory immunity to protect against future infections. In this Review, we highlight the biological mechanisms underlying strong humoral and cell-mediated immune responses and explore materials design strategies to manipulate and control these mechanisms.

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Section: Designing Spatial and Temporal Controlmentioning

confidence: 99%

Designing spatial and temporal control of vaccine responses

et al. 2021

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“…57 Instead of albumin hitchhiking, the direct fusion of an antigen peptide to albumin reduces systemic circulation and improved proteolytic stability, as fused proteins traffic to the lymph nodes or are captured by local APCs. 58 With optimized factors, this approach improves vaccine immunogenicity by up to 90-fold and maximizes the responses to viral antigens. 58 SARS-CoV-2 proteins or peptides can be modified with an albumin-binding domain or fused to a carrier protein for lymph node targeting.…”

Section: Route Of Vaccine Administration and Targetingmentioning

confidence: 99%

“…58 With optimized factors, this approach improves vaccine immunogenicity by up to 90-fold and maximizes the responses to viral antigens. 58 SARS-CoV-2 proteins or peptides can be modified with an albumin-binding domain or fused to a carrier protein for lymph node targeting. Elicio Therapeutics repurposed this type of platform and showed an improvement in SARS-CoV-2-specific cellular and humoral immune responses in mice.…”

Section: Route Of Vaccine Administration and Targetingmentioning

confidence: 99%

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

Zárubová

Zhang

Hoffman

et al. 2021

Matter

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Infection by SARS-CoV-2 virus often induces the dysregulation of immune responses, tissue damage, and blood clotting. Engineered biomaterials from the nano to macro scale can provide targeted drug delivery, controlled drug release, local immunomodulation, enhanced immunity, and other desirable functions to coordinate appropriate immune responses and repair tissues. Based on the understanding of COVID-19 disease progression and immune responses to SARS-CoV-2, we discuss possible immuno-therapeutic strategies and highlight biomaterial approaches from the perspectives of preventive immunization, therapeutic immunomodulation, and tissue healing and regeneration. Successful development of biomaterial platforms for immunization and immunomodulation will not only benefit COVID-19 patients, but also have broad applications for a variety of infectious diseases.

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“…fused tumor‐associated epitopes to minimally immunogenic carrier proteins such as albumin and transthyretin in order to control antigen degradation rates, biodistribution, and PK; they found that immunogenicity was maximized when using carrier proteins with prolonged residence time in local adjuvant‐inflamed draining lymph nodes. [ 124 ] Antigen‐carrier fusions mixed with cyclic di‐GMP, CpG, poly(I:C), or lipo‐CpG adjuvants greatly enhanced the antigen‐specific CD8 + T cell response after immunization. Schudel et al.…”

Section: Perspectives On the Future Of Trm Vaccine Designmentioning

confidence: 99%

Engineering Vaccines for Tissue‐Resident Memory T Cells

Knight

Wilson

2021

Advanced Therapeutics

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In recent years, tissue‐resident memory T cells (TRM) have attracted significant attention in the field of vaccine development. Distinct from central and effector memory T cells, TRM cells take up residence in home tissues such as the lung or urogenital tract and are ideally positioned to respond quickly to pathogen encounter. TRM are found to play a role in the immune response against many globally important infectious diseases for which new or improved vaccines are needed, including influenza and tuberculosis. It is also increasingly clear that TRM play a pivotal role in cancer immunity. Thus, vaccines that can generate this memory T cell population are highly desirable. The field of immunoengineering—that is, the application of engineering principles to study the immune system and design new and improved therapies that harness or modulate immune responses—is ideally poised to provide solutions to this need for next‐generation TRM vaccines. This review covers recent developments in vaccine technologies for generating TRM and protecting against infection and cancer, including viral vectors, virus‐like particles, and synthetic and natural biomaterials. In addition, it offers critical insights on the future of engineering vaccines for tissue‐resident memory T cells.

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Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines

Cited by 48 publications

References 64 publications

Designing spatial and temporal control of vaccine responses

Designing spatial and temporal control of vaccine responses

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases

Engineering Vaccines for Tissue‐Resident Memory T Cells

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