Sustained delivery approaches to improving adaptive immune responses

Ou, Ben S.; Saouaf, Olivia; Baillet, Julie; Appel, Eric A.

doi:10.1016/j.addr.2022.114401

Cited by 54 publications

(43 citation statements)

References 222 publications

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“…[57][58][59] Harnessing other vaccine advances such as hydrogel-based sustained release strategies for continuous immune stimulation, or the use of alternative adjuvants like saponin/MPLA may also increase the potency of NHR targeting vaccines. 60,61 The structural, binding and immunization results presented here indicate that epitope conformation and rigidity can be engineered to bias the population of elicited antibodies in a vaccine context. Our findings also suggest that protein engineering can improve the gp41 pocket as a vaccine target and provide support that targeting the PHI is an orthogonal and complimentary approach to current HIV-1 germline-targeting vaccine efforts.…”

Section: Discussionmentioning

confidence: 93%

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Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies

Bruun

Tang

Erwin

et al. 2022

Preprint

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The hydrophobic pocket found in the N-heptad repeat (NHR) region of HIV-1 gp41 is a highly conserved epitope that is the target of various HIV-1 neutralizing monoclonal antibodies. Although the high conservation of the pocket makes it an attractive vaccine candidate, it has been challenging to elicit potent anti-NHR antibodies via immunization. Here, we solved a high-resolution structure of the NHR mimetic IQN17, and, consistent with previous ligand-bound gp41 pocket structures, we observed remarkable conformational plasticity of the pocket. The high malleability of this pocket led us to test whether we could improve the immunogenicity of the gp41 pocket by stabilizing its conformation. We show that the addition of five amino acids at the C-terminus of IQN17, to generate IQN22, introduces a stabilizing salt bridge at the base of the peptide that rigidifies the pocket. Mice immunized with IQN22 elicited higher avidity antibodies against the gp41 pocket and a more potent, albeit still weak, neutralizing response against HIV-1 compared to IQN17. Stabilized epitope-focused immunogens could serve as the basis for future HIV-1 fusion-inhibiting vaccines.

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Section: Discussionmentioning

confidence: 93%

“…57–59 Harnessing other vaccine advances such as hydrogel-based sustained release strategies for continuous immune stimulation, or the use of alternative adjuvants like saponin/MPLA may also increase the potency of NHR targeting vaccines. 60,61…”

Section: Discussionmentioning

confidence: 99%

Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies

Bruun

Tang

Erwin

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Interestingly, although the main activity of delivery systems is to facilitate the specific antigen uptake by immune system cells, some have integrated composition, showing potent immunomodulatory activities [175]. As seen previously, systems that have cationic materials and synthetic polymers such as PEI and PAMAM can be recognized by immune system cells, potentiating the immune response [164].…”

Section: Microorganism-based Delivery Systemsmentioning

confidence: 98%

“…Finally, some delivery systems, in addition to acting as carrier molecules, have inherent adjuvant characteristics and can therefore assist in polarizing the immune response [175]. Depending on the composition of the carrier molecule, they can be recognized by DCs by receptors such as Toll-like receptors (TLRs), NOD, RIG, and Dectin-1 by identifying molecular patterns (Figure 2).…”

Section: The Influence Of Delivery Systems On the Immune Responsementioning

confidence: 99%

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

et al. 2022

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Prophylactic vaccines against human papillomavirus (HPV) have proven efficacy in those who have not been infected by the virus. However, they do not benefit patients with established tumors. Therefore, the development of therapeutic options for HPV-related malignancies is critical. Third-generation vaccines based on nucleic acids are fast and simple approaches to eliciting adaptive immune responses. However, techniques to boost immunogenicity, reduce degradation, and facilitate their capture by immune cells are frequently required. One option to overcome this constraint is to employ delivery systems that allow selective antigen absorption and help modulate the immune response. This review aimed to discuss the influence of these different systems on the response generated by nucleic acid vaccines. The results indicate that delivery systems based on lipids, polymers, and microorganisms such as yeasts can be used to ensure the stability and transport of nucleic acid vaccines to their respective protein synthesis compartments. Thus, in view of the limitations of nucleic acid-based vaccines, it is important to consider the type of delivery system to be used—due to its impact on the immune response and desired final effect.

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“…The controlled release of active molecules is widely regarded as an essential technology in pharmaceutics, food manufacturing, and agriculture. − In these scientific and industrial areas, the functional molecules could induce diverse biological responses by stimulating specific organisms, such as immune defense, pollinator attraction, nutrient secretion, or even influencing human emotions and behavior. − These physiological responses, however, can only be activated when the molecules accumulate at the appropriate levels, meaning that the controlled release of molecules is essential to achieve specific functions. Fragrance molecules generally induce sensory perception by stimulating the olfactory cells in the nasal cavity.…”

Section: Introductionmentioning

confidence: 99%

Copper(I)-Iodide Clusters as Carriers for Regulating and Visualizing Release of Aroma Molecules

Zhang

Dai

et al. 2023

ACS Appl. Mater. Interfaces

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Achieving the controlled release of functional substances is indispensable in many aspects of life. Especially for the aroma molecules, their effective delivery of flavor and fragrance is challenging. Here, selected pyridines, as highly volatile odorants, were individually coordinated with copper(I) iodide (CuII) via a straightforward one-pot synthesis method, rapidly forming pure or even crystalline CuII cluster-based profragrances at room temperature. The obtained profragrances enabled the stable and high loading of volatile fragrances under ambient conditions and guaranteed their long-lasting release during heating. Furthermore, the intrinsic emission luminescence of these solid-state profragrances decayed along with the aroma release, which can serve as an additional indicator for monitoring the delivery process. This research sets a precedent for using CuII clusters as dual-purpose release agents and greatly expands their potential applications.

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Sustained delivery approaches to improving adaptive immune responses

Cited by 54 publications

References 222 publications

Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies

Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

Copper(I)-Iodide Clusters as Carriers for Regulating and Visualizing Release of Aroma Molecules

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