The precipitation of diphtheria toxoid by potash alum

Glenny, A. T.; Barr, Mollie

doi:10.1002/path.1700340203

Cited by 52 publications

(21 citation statements)

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“…Ramon first provided information indicating that inflammation caused by co-administration of various chemicals such as oils and extracts of tapioca facilitated elevated antibody production in horses [22]. Glenny was the first to co-administer aluminum salts with antigen and Freund later developed oil emulsions containing inactivated mycobacterium tuberculosis to enhance the immune response [19,23,24]. More recently, studies have examined the effect of combinations of Al(OH) 3 and oil-emulsion adjuvants when hyperimmunizing sheep [25–27].…”

Section: Discussionmentioning

confidence: 99%

New equine antitoxins to botulinum neurotoxins serotypes A and B

Mattoo

Keller

2012

Biologicals

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Hyperimmune monovalent antitoxins to botulinum neurotoxin serotypes A and B have been produced by immunizing horses with newly developed formalin toxoids. After primary immunization horses were found to have developed acceptable prophylactic antibody titers (1–5 IU/mL). Three horses received additional toxoid booster injections to induce hyperimmune antibody titers with antitoxin-A and antitoxin-B titers reaching peaks of approximately 2000 IU/mL and 150–625 IU/mL, respectively. Titers were quantified throughout the process by antigen-capture ELISA and by in-vivo neutralization. ELISA titers and neutralization titers correlated (R2 ~0.62–0.92), however, unique correlations between in-vitro and in-vivo titers were observed for each animal. Monovalent antitoxin pools were made by combining plasma that had been collected twice via plasmapheresis several months after primary immunization. Neutralizing units were established for each pool relative to the current US and WHO reference standards. Titers were determined at the L+/10 and L+/40 toxin dose for Toxin types A and B, respectively, and both U.S. and international units assigned to each monovalent antitoxin. Avidity of the new Anti-A pool was equivalent to the WHO Anti-A reference at the L+, L+/10 and L+/30 dose. Each monovalent plasma pool failed to cross-neutralize other botulinum neurotoxin serotypes indicating a high degree of specificity of each antitoxin for the toxin serotype used during immunization.

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Section: Discussionmentioning

confidence: 99%

New equine antitoxins to botulinum neurotoxins serotypes A and B

Mattoo

Keller

2012

Biologicals

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“…These issues inspired early vaccinologists to explore the use of vaccines that instead contained either whole, killed microbes or components of microbes against which effective lasting immunity could be established. In the 1920s and 30s, Alexander Glenny demonstrated that the precipitation of Diphtheria toxoid on an aluminum salt dramatically enhanced the efficacy of the subunit vaccine to elicit anti sera [16–18]. This milestone not only marked the dawn of vaccine adjuvants, it also helped inextricably link neutralizing antibody formation as the gold standard metric for evaluating vaccine efficacy.…”

Section: B Cell Vaccinology… a Better Reflection Of Infectionmentioning

confidence: 99%

T Cell Vaccinology: Beyond the Reflection of Infectious Responses

Pennock

Kedl

2016

Trends in Immunology

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Inducing sustained, robust CD8+ T cell responses is necessary for therapeutic intervention in chronic infectious diseases and cancer. Unfortunately, most adjuvant formulations fail to induce substantial cellular immunity in humans. Attenuated acute infectious agents induce strong CD8+ T cell immunity, and are thought to therefore represent a good road map for guiding the development of subunit vaccines capable of inducing the same. However, recent evidence suggests that this assumption may need reconsideration. Here we provide an overview of subunit vaccine history as it pertains to instigating T cell responses. We argue that in light of evidence demonstrating that T cell responses to vaccination differ from those induced by infectious challenge, research in pursuit of cellular immunity-inducing vaccine adjuvants should no longer follow only the infection paradigm.

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“…For more than 70 years, the only vaccine adjuvant knowingly used as such was alum. Glenny initially described the immuneenhancing properties of aluminum hydroxide when administered with diphtheria toxin in 1926 (15). Since that time, aluminum salts have been a critical component of a variety of vaccines, including those targeting diphtheria, tetanus, pertussis, hepatitis B, and HPV.…”

Section: Introductionmentioning

confidence: 99%

Developing vaccines for an aging population

2015

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The demographics of the world's population are changing, with many adults now surviving into their 80s. With this change comes the need to protect the aging and other underserved populations not only against infectious diseases but also against cancer and other chronic conditions. New technologies derived from recent advances in the fields of immunology, structural biology, synthetic biology, and genomics have brought a revolution in the vaccine field. Among them, vaccine adjuvants have the potential to harness the immune system to provide protection against new types of diseases, improve protection in young children, and expand this protection to adults and the elderly. However, in order to do so we need also to overcome the nontechnical challenges that could limit the implementation of innovative vaccines, including controversies regarding the safety of adjuvants, increasing regulatory complexity, the inadequate methods used to assess the value of novel vaccines, and the resulting industry alienation from future investment. This Perspective summarizes the outcome of a recent multidisciplinary symposium entitled "Enhancing Vaccine Immunity and Value," held in Siena, Italy, in July 2014, that addressed two related questions: how to improve vaccine efficacy by using breakthrough technologies and how to capture the full potential of novel vaccines.

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The precipitation of diphtheria toxoid by potash alum

Cited by 52 publications

References 1 publication

New equine antitoxins to botulinum neurotoxins serotypes A and B

New equine antitoxins to botulinum neurotoxins serotypes A and B

T Cell Vaccinology: Beyond the Reflection of Infectious Responses

Developing vaccines for an aging population

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