Immunological notes. XVII–XXIV

Glenny, A. T.; Pope, C. G.; Waddington, Hilda; Wallace, U.

doi:10.1002/path.1700290106

Cited by 364 publications

(156 citation statements)

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“…Since the discovery of the adjuvant activity of aluminum compounds 80 years ago [1], over 100 empirically-derived adjuvants and adjuvant variations have been tested both preclinically and clinically [2]. Nearly all of these adjuvants failed to win approval for use in routine vaccines due to toxicity concerns.…”

Section: Introductionmentioning

confidence: 99%

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Zaharoff

Rogers

Hance

et al. 2007

Vaccine

311

193

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The development of safe, novel adjuvants is necessary to maximize the efficacy of new and/or available vaccines. Chitosan is a non-toxic, biocompatible, biodegradable, natural polysaccharide derived from the exoskeletons of crustaceans and insects. Chitosan's biodegradability, immunological activity and high viscosity make it an excellent candidate as a depot/adjuvant for parenteral vaccination. To this end, we explored chitosan solution as an adjuvant for subcutaneous vaccination of mice with a model protein antigen. We found that chitosan enhanced antigen-specific antibody titers over 5-fold and antigen-specific splenic CD4 + proliferation over 6-fold. Strong increases in antibody titers together with robust delayed-type hypersensitivity (DTH) responses revealed that chitosan induced both humoral and cell-mediated immune responses. When compared with traditional vaccine adjuvants, chitosan was equipotent to incomplete Freund's adjuvant (IFA) and superior to aluminum hydroxide. Mechanistic studies revealed that chitosan exhibited at least two characteristics that may allow it to function as an immune adjuvant. First, the viscous chitosan solution created an antigen depot. More specifically, less than 9% of a protein antigen, when delivered in saline, remained at the injection site after 8 hours. However, more than 60% of a protein antigen delivered in chitosan remained at the injection site for 7 days. Second, chitosan induced a transient 67% cellular expansion in draining lymph nodes. The expansion peaked between 14 and 21 days after chitosan injection and diminished as the polysaccharide was degraded. These mechanistic studies, taken together with the enhancement of a vaccine response, demonstrate that chitosan is a promising and safe platform for parenteral vaccine delivery.

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Section: Introductionmentioning

confidence: 99%

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Zaharoff

Rogers

Hance

et al. 2007

Vaccine

311

193

View full text Add to dashboard Cite

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“…Adjuvants have been used to improve vaccine efficacy from the early 1920's (1,2). In 1926, Glenny demonstrated the adjuvant activity of aluminum compounds (1). More than ten years later, in the late 1930s, Freund developed his water-in-oil/ oil-in-water emulsion containing killed mycobacteria (3).…”

Section: Contextmentioning

confidence: 99%

“…Adjuvants are compounds that enhance the immune response against co-inoculated antigens with the word adjuvant coming from the Latin word adjuvare (to help or to enhance). Adjuvants have been used to improve vaccine efficacy from the early 1920's (1,2). In 1926, Glenny demonstrated the adjuvant activity of aluminum compounds (1).…”

Section: Contextmentioning

confidence: 99%

Vaccine Adjuvants: The Current Necessity of Life

Gupta

Chaphalkar

2015

Shiraz E-Med J

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Context:Vaccination is considered as the most cost effective method for the prevention of human diseases. For this prevention method, we need certain substances to increase or boost the antibody as well as cell-mediated immune response against various bacterial as well as viral pathogens. Until now, alum was considered as the safest adjuvant for human use, licensed by the United States Food and Drug Administration. Due to the poor adjuvanticity of alum, conventional vaccines require multiple recall injections, at different time intervals, to attain or sustain the optimal immune response. The present review discusses about the necessity of adjuvants for vaccines. Evidence Acquisition: A number of factors such as slow release of antigen (depot effect), more efficient delivery of antigen to draining lymph nodes, non-specific activation of antigen-presenting cells or of B and/or T-lymphocytes, increased uptake of antigen by antigenpresenting cells or increased recruitment of immune cells to the site where the antigen is present, can contribute to increased immune responses to immunization. Many of these factors involve the interaction of various immune system components and specific anatomical features, making them difficult to replicate in model systems in vitro. Results: Despite the development of many potent adjuvant formulations with vaccine antigen during the last 80 -90 years, aluminum compounds are still the only approved adjuvants used for routine human vaccines. Conclusions: Based on pre-clinical and preliminary clinical observations, it appears that the range of adjuvants accepted for human vaccines will expand in the coming years.

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“…This was followed up by Glenny and co-workers, who in 1926 demonstrated that diphtheria toxoid precipitated with aluminum salts resulted in significant increase of the immune response to the toxoid. 3 During the 1930's aluminum salts were for the first time used as adjuvants in human vaccines against diphtheria, pertussis and tetanus and are now also found in vaccines against hepatitis A and B, Haemophilus influenzae type b, pneumococcus and human papilloma virus. It is worth noting that the addition of an adjuvant in these vaccines is a crucial element for them to be effective and it is well established that aluminum salts facilitate higher and longer-lasting immunity.…”

Section: Adjuvants In Licensed Vaccinesmentioning

confidence: 99%

Vaccine adjuvants: Why and how

Christensen

2016

Human Vaccines & Immunotherapeutics

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Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.

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Immunological notes. XVII–XXIV

Cited by 364 publications

References 0 publications

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination

Vaccine Adjuvants: The Current Necessity of Life

Vaccine adjuvants: Why and how

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