Adjuvants for Protein‐ and Carbohydrate‐Based Vaccines

Guy, Bruno

doi:10.1002/9780470473283.ch3

Cited by 6 publications

(12 citation statements)

References 149 publications

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“…Since GM3 itself, including its protein conjugates (4), is poorly immunogenic and elicits almost only IgM antibodies, the immunological results of 1 suggest that MPLA as a carrier molecule can effectively improve the immunogenicity of GM3 and help elicit T cell-dependent immunity. In addition, because effective vaccination typically requires a vaccine adjuvant (29) but no external adjuvant was utilized in the immunization with 1 , MPLA can also act as a built-in adjuvant.…”

Section: Resultsmentioning

confidence: 99%

Carbohydrate-Monophosphoryl Lipid A Conjugates Are Fully Synthetic Self-Adjuvanting Cancer Vaccines Eliciting Robust Immune Responses in the Mouse

et al. 2011

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Tumor-associated carbohydrate antigens (TACAs) are useful targets in the development of therapeutic cancer vaccines. However, a serious problem with them is the poor immunogenicity. To overcome the problem, a monophosphorylated derivative of Neisseria meningitidis lipid A was explored as a potential carrier molecule and built-in adjuvant for the construction of structurally defined fully synthetic glycoconjugate vaccines. Some paradigm-shifting discoveries about the monophosphoryl lipid A (MPLA)-TACA conjugates were that they elicited robust IgG antibody responses, indicating T cell-mediated immunity, without an external adjuvant and that an external adjuvant, e.g., Titermax Gold, actually reduced, instead of promoting, the immunological activity of the conjugates. The induced antibodies were proved to bind selectively to target tumor cells. MPLA was therefore demonstrated to be a powerful built-in immunostimulant and adjuvant for an all new design of fully synthetic glycoconjugate cancer vaccines.

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Section: Resultsmentioning

confidence: 99%

Carbohydrate-Monophosphoryl Lipid A Conjugates Are Fully Synthetic Self-Adjuvanting Cancer Vaccines Eliciting Robust Immune Responses in the Mouse

et al. 2011

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“…The two main basic mechanisms by which adjuvants act are enhancing antigen presentation to the immune elements and stimulating immunity so that a stronger or wider response is reached. By these means, immunogenicity can be improved and/or doses of the vaccines can be decreased to a level that has no negative effect on immunogenicity [ 47 , 48 ].…”

Section: Hib Vaccinesmentioning

confidence: 99%

“…The primary mineral salt adjuvant for use in humans is alum, either as aluminum hydroxide or as aluminum phosphate. It acts by creating a depot spot, such that mild and constant release of the antigen improves presentation to immunological components [ 47 , 48 ].…”

Section: Hib Vaccinesmentioning

confidence: 99%

“…APCs class I presentation for CD8 stimulation may be controlled by these signals. Promotion of CD4 cells that secrete interferon gamma (IFNg) by Th1 adjuvants is not enough to activate CD8 cytotoxic T cells, which also need class I antigen presentation [ 48 ]. These outcomes closely connect native immunity and the following adaptive immunity.…”

Section: Hib Vaccinesmentioning

confidence: 99%

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Hib Vaccines: Past, Present, and Future Perspectives

Zarei

Almehdar

Redwan

2016

Journal of Immunology Research

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Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.

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“…Carbohydrates as therapeutics must fulfill strict requirements in terms of homogeneity and purity and their preparation is associated with different technical problems regarding their chemical synthesis, the biological techniques used etc (53,54). Several carbohydrate-based drugs are already on the market, and many others are in various phases of clinical trials (55).…”

Section: Carbohydrates In Therapy and Diagnosticsmentioning

confidence: 99%

Glycans as Biomarkers: Status and Perspectives

Janković¹

2011

Journal of Medical Biochemistry

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lanaca koji su kovalentno vezani za poli pep tidnu ki~mu. Dobro je poznat zna~aj prome na u glikozilaciji proteina za nastanak, razvoj i krajnji ishod razli~itih bolesti kod ljudi. Glikani se smatraju jedinstvenim strukturama za di jag nozu, i pra}enje toka bolesti. U »omics« eri, glikom, glika n ski analog proteoma i genoma, predstavlja mogu}i izvor no vih biomarkera. Kreiranje strategije za otkri}e biomarkera zahteva nove principe i platforme za analizu relativno malih koli~ina brojnih glikoproteina. O~ekuje se da glikomske teh no logije, koje su jo{ u razvoju, a koje obuhvataju razli~ite tipove masene spektrometrije i afinitivnih tehnika, rezultiraju novim analiti~kim procedurama u oblasti odre |i vanja bio markera. Najve}i izazovi za eksperimentalnu i kli ni~ku gliko pro teomiku su: pretraga razli~itih tipova gliko mo lekula, oda bir potencijalnih markera i njihova selekcija ili pre ~i{}a -vanje i identifikacija. Za ovo je neophodno razviti teh no logije koje }e omogu}iti visoku senzitivnost detekcije biomarkera kao i odgovaraju}u standardizaciju i validaciju novih metoda, kako bi se one mogle primeniti u laboratorijskom radu. Dalji razvoj na polju primenjene glikonauke zahteva integrisani sistemski pristup sa ciljem da se na pravi na~in iskoriste sve njene mo gu}nosti u dijagnostici.

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Adjuvants for Protein‐ and Carbohydrate‐Based Vaccines

Cited by 6 publications

References 149 publications

Carbohydrate-Monophosphoryl Lipid A Conjugates Are Fully Synthetic Self-Adjuvanting Cancer Vaccines Eliciting Robust Immune Responses in the Mouse

Carbohydrate-Monophosphoryl Lipid A Conjugates Are Fully Synthetic Self-Adjuvanting Cancer Vaccines Eliciting Robust Immune Responses in the Mouse

Hib Vaccines: Past, Present, and Future Perspectives

Glycans as Biomarkers: Status and Perspectives

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