Advantages of Aluminium Hydroxide Adsorbed Combined Diphtheria, Tetanus, and Pertussis Vaccines for the Immunization of Infants

Butler, N. R.; Voyce, M. A.; Burland, W. L.; Hilton, Marjorie L.

doi:10.1136/bmj.1.5645.663

Cited by 91 publications

(39 citation statements)

References 8 publications

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“…The MWGT for whole cell pertussis vaccines has been reported to be correlated with some adverse reactions in children. 50,51 Our results suggest that this test may not be sufficiently sensitive to evaluate CyaA toxicity, in agreement with a previous report of similar results with CyaA preparations at lower doses and two injections. 52 The discrepancy between the in vitro and in vivo results could be caused by differences in the assay sensitivity of these two systems.…”

Section: In Vivo Evaluationsupporting

confidence: 81%

Development of an Approach for the Laboratory Toxicological Evaluation ofBordetella PertussisAdenylate Cyclase Genetic Toxoid Constructs as Multipurpose Vaccine

Prior¹,

Corbel²,

Xing³

2005

Human Vaccines

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Detoxified recombinant CyaA constructs have been developed as potential viral and tumoral epitope carriers for immunoprophylactic and therapeutic vaccination and as antigen candidates for inclusion in acellular pertussis vaccines. In this work, we attempt to explore a test system for the laboratory safety evaluation of CyaA preparations. Endotoxin was determined in vitro by the Limulus amoebocyte lysate assay. Cytotoxicity was measured by a tetrazolium salt test and a lactate dehydrogenase release assay using murine and human phagocytic cell lines. Cell viability was < 50% at concentrations > 1 µg/mL of the wild type toxin and concentrations in the nanogram range inhibited the zymosan-induced oxidative burst as measured by chemiluminescence. However, no effects were observed for detoxified and non-acylated forms of CyaA at comparable and higher toxin concentrations. Effects found in the in vitro assays could not be related to the in vivo mouse weight gain test used as a general toxicity test. In vitro cytotoxicity and oxidative burst studies on phagocytes, and the evaluation of endotoxin levels are useful for safety screening of CyaA constructs. However, in vivo specific toxicity tests and potential toxic implications of enzymatic activity-independent effects of CyaA on cell function should be investigated. ABBREVIATIONSCyaA, adenylate cyclase toxin; MHC, major histocompatibility complex; CTL, cytotoxic T lymphocyte; cAMP, cyclic adenosine monophosphate; CyaA-wt, wild type adenylate cyclase toxin; CyaA-E5, detoxified adenylate cyclase toxin; proCyaA-wt, wild type adenylate cyclase protoxin; proCyaA-E5, detoxified adenylate cyclase protoxin; CyaA-E5-Tyros, detoxified adenylate cyclase toxin with tyrosinase epitope

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Section: In Vivo Evaluationsupporting

confidence: 81%

Development of an Approach for the Laboratory Toxicological Evaluation ofBordetella PertussisAdenylate Cyclase Genetic Toxoid Constructs as Multipurpose Vaccine

Prior¹,

Corbel²,

Xing³

2005

Human Vaccines

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“…The incorporation of adjuvant in the vaccine. Thus they confirm the conclusions of Feldman (1957) and Butler, Voyce, Burland & Hilton (1969) that adjuvant improves the agglutinin-response to pertussis vaccination, and they show also the extent to which this improvement applies to each of the three major pertussis antigens.…”

Section: Pertussis Agglutinins In Normal Serasupporting

confidence: 75%

Pertussis agglutinins in vaccinated children: better response with adjuvant

Preston

Mackay

Bamford

et al. 1974

J. Hyg.

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SUMMARYChildren were immunized with a single batch of pertussis vaccine, either adsorbed on aluminium hydroxide or plain. With a primary course of three injections, adsorbed vaccine produced higher titres of pertussis agglutinins in the serum than did plain vaccine. There was no obvious difference in response between those who received the three doses at intervals of 1-2 months, starting at 3-4 months of age, and those in whom the third dose was delayed until about 6 months after the second, but the number of children in each group was small.

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“…There is a high proportion of moderate to severe granulomas when alum-based vaccines are injected subcutaneously or intradermally [8,9]. Other limitations of alum adjuvants are increased IgE production, allergenicity and neurotoxicity [8,[10][11][12].…”

Section: Toxicity Of Alum-based Adjuvantsmentioning

confidence: 99%

“…Other limitations of alum adjuvants are increased IgE production, allergenicity and neurotoxicity [8,[10][11][12]. Under conditions of reduced renal function, aluminium is accumulated in the body and becomes highly toxic causing fatal neurological syndrome and dialysis-associated dementia.…”

Section: Toxicity Of Alum-based Adjuvantsmentioning

confidence: 99%

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Petrovsky

2006

Vaccine

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Pure soluble, recombinant and synthetic antigens, despite their better tolerability, are unfortunately often much less immunogenic than live or killed whole organism vaccines. Thus, the move towards the development of safer subunit vaccines has created a major need for more potent adjuvants. In particular, there is an urgent need for adjuvants capable of boosting cellular (Th1) immunity but without unacceptable toxicity. The adjuvant activity of aluminium compounds (aluminium phosphate or hydroxide) was first described by Glenny and colleagues in 1926. Surprisingly, despite the description of over one hundred adjuvants in the scientific literature, alum remains the only adjuvant approved for human use in the USA. Unfortunately, alum has no effect on cellular immunity and is faced with increasing concerns regarding potential for cumulative aluminium toxicity. Why then has alum not been replaced in human vaccines? Despite the enormous number of candidates, potency has invariably been associated with increased toxicity, and this more than anything else has precluded their use, particularly in prophylactic vaccines where safety issues are paramount. Hence, there is a major unmet need for a safe efficacious adjuvant capable of boosting cellular plus humoral immunity. The extensive data on inulin-based adjuvants indicate that these are excellent candidates to replace alum as the adjuvant of choice for many vaccines. Particular advantages offered by inulin-based adjuvants is that they induce cellular in addition to humoral immunity and offer excellent safety, tolerability, ease of manufacture and formulation. Thus, adjuvants based on inulin have enormous potential for use in vaccines against both pathogens and cancer.

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Advantages of Aluminium Hydroxide Adsorbed Combined Diphtheria, Tetanus, and Pertussis Vaccines for the Immunization of Infants

Cited by 91 publications

References 8 publications

Development of an Approach for the Laboratory Toxicological Evaluation ofBordetella PertussisAdenylate Cyclase Genetic Toxoid Constructs as Multipurpose Vaccine

Development of an Approach for the Laboratory Toxicological Evaluation ofBordetella PertussisAdenylate Cyclase Genetic Toxoid Constructs as Multipurpose Vaccine

Pertussis agglutinins in vaccinated children: better response with adjuvant

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

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