Minimal immunogen vaccines are being developed to focus antibody responses against otherwise challenging targets, including human immunodeficiency virus (HIV), but multimerization of the minimal peptide immunogen on a carrier platform is required for activity. Star copolymers comprising multiple hydrophilic polymer chains ("arms") radiating from a central dendrimer unit ("core") were recently reported to be an effective platform for arraying minimal immunogens for inducing antibody responses in mice and primates. However, the impact of different parameters of the star copolymer (e.g., minimal immunogen density and hydrodynamic size) on antibody responses and the optimal synthetic route for controlling those parameters remains to be fully explored. We synthesized a library of star copolymers composed of poly[N-(2-hydroxypropyl)methacrylamide] hydrophilic arms extending from poly(amidoamine) dendrimer cores with the aim of identifying the optimal composition for use as minimal immunogen vaccines. Our results show that the length of the polymer arms has a crucial impact on the star copolymer hydrodynamic size and is precisely tunable over a range of 20-50 nm diameter, while the dendrimer generation affects the maximum number of arms (and therefore minimal immunogens) that can be attached to the surface of the dendrimer. In addition, high-resolution images of selected star copolymer taken by a custom-modified environmental scanning electron microscope enabled the acquisition of high-resolution images, providing new insights into the star copolymer structure. Finally, in vivo studies assessing a star copolymer vaccine comprising an HIV minimal immunogen showed the criticality of polymer arm length in promoting antibody responses and highlighting the importance of composition tunability to yield the desired biological effect.

• MeSH
• dendrimery * chemie   MeSH
• lidé MeSH
• myši MeSH
• nosiče léků chemie   MeSH
• polyaminy MeSH
• polymery chemie   MeSH
• vakcíny proti AIDS imunologie   chemie   aplikace a dávkování   MeSH
• vakcíny imunologie   chemie   aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dendrimery * MeSH
• nosiče léků MeSH
• Poly(amidoamine) MeSH Prohlížeč
• polyaminy MeSH
• polymery MeSH
• vakcíny proti AIDS MeSH
• vakcíny MeSH

Neuroimmunological diseases and their treatment compromise the immune system, thereby increasing the risk of infections and serious illness. Consequently, vaccinations to protect against infections are an important part of the clinical management of these diseases. However, the wide variety of immunotherapies that are currently used to treat neuroimmunological disease - particularly multiple sclerosis and neuromyelitis optica spectrum disorders - can also impair immunological responses to vaccinations. In this Review, we discuss what is known about the effects of various immunotherapies on immunological responses to vaccines and what these effects mean for the safe and effective use of vaccines in patients with a neuroimmunological disease. The success of vaccination in patients receiving immunotherapy largely depends on the specific mode of action of the immunotherapy. To minimize the risk of infection when using immunotherapy, assessment of immune status and exclusion of underlying chronic infections before initiation of therapy are essential. Selection of the required vaccinations and leaving appropriate time intervals between vaccination and administration of immunotherapy can help to safeguard patients. We also discuss the rapidly evolving knowledge of how immunotherapies affect responses to SARS-CoV-2 vaccines and how these effects should influence the management of patients on these therapies during the COVID-19 pandemic.

• MeSH
• COVID-19 * prevence a kontrola   MeSH
• imunologické faktory MeSH
• imunoterapie MeSH
• lidé MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• vakcinace MeSH
• vakcíny proti COVID-19 * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• imunologické faktory MeSH
• vakcíny proti COVID-19 * MeSH

The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST' was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials.

• Klíčová slova
• Pertussis vaccines, histamine sensitisation test, replacement alternative,
• MeSH
• acelulární vakcíny terapeutické užití   MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• histamin aplikace a dávkování   MeSH
• křečci praví MeSH
• lidé MeSH
• myši MeSH
• pertuse diagnóza   prevence a kontrola   MeSH
• pertusová vakcína terapeutické užití   MeSH
• pertusový toxin terapeutické užití   MeSH
• výchova a vzdělávání metody   trendy   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• kongresy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• acelulární vakcíny MeSH
• histamin MeSH
• pertusová vakcína MeSH
• pertusový toxin MeSH

The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer-TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer-TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer-TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer-TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.

• MeSH
• adjuvancia imunologická chemie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nosiče léků chemie   MeSH
• T-lymfocyty imunologie   MeSH
• toll-like receptory agonisté   MeSH
• vakcíny imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• nosiče léků MeSH
• toll-like receptory MeSH
• vakcíny MeSH