Dose site reactions and related findings after vaccine administration in safety studies

Baldrick, Paul

doi:10.1002/jat.3314

Cited by 37 publications

(24 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subcutaneous administration of ADP at MTD during 7 consecutive days was well tolerated. Injection site reactions were observed and attributed to the aluminum hydroxide as reported with other vaccines containing this adjuvant . Some hematological alterations were detected such as an increase in blood neutrophil count and globulin, and a decrease in albumin.…”

Section: Discussionmentioning

confidence: 65%

Preclinical safety and immunological efficacy of Alternaria alternata polymerized extracts

Morales¹,

Gallego²,

Iraola³

et al. 2017

Immunity Inflam & Disease

View full text Add to dashboard Cite

Introduction Alternaria alternata is a widespread fungi whose allergy is a risk factor for asthma development. The use of a polymerized allergen extract (allergoid) may be safer than native extract based treatments while maintaining efficacy. The objective of this study was to characterize biochemically and immunochemically a new Alternaria alternata allergoid.MethodsCharacterization of native and allergoid extracts was performed by determination of protein content, protein and allergenic profile, biological potency, identification of Alternaria allergens, and Alt a 1 quantification. Safety was evaluated in toxicological assays (Ames test, limit test, and fish embryo acute toxicity test in zebrafish, and maximum tolerated dose and Dose‐range finding study in rats). Efficacy was evaluated as the capacity to induce IgG antibodies that block IgE‐binding to the allergen and cytokine induction (IFN‐γ, IL‐4, IL‐6, IL‐10, and TNF‐α) in PBMC from atopic donors.ResultsProtein and antigenic profiles showed significant modification of the depigmented allergoid with respect to the native extract, inducing a lower IgE binding capacity. Alt a 1, Alt a 3, Alt a 6, and Alt a 8 allergen sequences were identified in the polymer. No toxicological nor genotoxicity effects were observed. The polymer induced IgG antibodies that blocked human IgE binding epitopes, and it induced higher IL‐10 levels and similar levels of the other cytokines than native extract in PBMC.ConclusionsThis new A. alternata allergoid could be an effective immunotherapy treatment leading to cytokine stimulation and inducing synthesis of IgG antibodies able to block IgE binding to the allergen. In addition, no toxicological effect was observed, and it may be safer than native extract due to its lower IgE binding capacity and cytokine induction that suggest tolerance induction via T cell shift to Treg (IL‐10).

show abstract

Section: Discussionmentioning

confidence: 65%

Preclinical safety and immunological efficacy of Alternaria alternata polymerized extracts

Morales¹,

Gallego²,

Iraola³

et al. 2017

Immunity Inflam & Disease

View full text Add to dashboard Cite

show abstract

“…ProteqFlu-Te®). 31 A dose of 2000 µg was then selected as a reasonable high dose for humans after this dose was found to be safe and active following three consecutive IM injections in the rabbit, the usual species for vaccine/adjuvant safety evaluation. 32 In the present immunogenicity study in macaques, no safety signal was observed in any of the vaccine groups, based on clinical observations, blood biochemistry and complete blood counts.…”

Section: Discussionmentioning

confidence: 99%

A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques

Pavot

Bisceglia

Guillaume

et al. 2021

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Adjuvants are central to the efficacy of subunit vaccines. Although several new adjuvants have been approved in human vaccines over the last decade, the panel of adjuvants in licensed human vaccines remains small. There is still a need for novel adjuvants that can be safely used in humans, easy to source and to formulate with a wide range of antigens and would be broadly applicable to a wide range of vaccines. In this article, using the Respiratory Syncytial Virus (RSV) nanoparticulate prefusion F model antigen developed by Sanofi, we demonstrate in the macaque model that the polyacrylate (PAA)-based adjuvant SPA09 is well tolerated and increases vaccine antigen-specific humoral immunity (sustained neutralizing antibodies, memory B cells and mucosal immunity) and elicits strong T H 1-type responses (based on IFNγ and IL-2 ELISpots) in a dose-dependent manner. These data warrant further development of the SPA09 adjuvant for evaluation in clinical trial.

show abstract

“…Thus, both systemic and dose site effects are likely due to the action of the immunostimulatory nature of MPL and/or the presence of l ‐tyrosine within the adjuvanted vaccine. More recently, a review of toxicity studies with 30 different adjuvanted vaccines showed common study findings of altered clinical pathology parameters (commonly raised blood neutrophil count and increased globulin levels, but also raised fibrinogen) and evidence of inflammation at the dose site (Baldrick, ). It was concluded that clinical pathological and injection site changes can be interpreted as related to an expected reaction after vaccine dosing, with generation of an immune response largely because of the presence of adjuvant, although direct vaccine antigen involvement was also occasionally demonstrated by the presence of a slightly increased inflammatory response seen over adjuvant treatment only.…”

Section: Discussionmentioning

confidence: 99%

New toxicity testing of PQ grass allergy immunotherapy to support product development

Baldrick

Hutchings

Heath

et al. 2019

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

PQ Grass represents an allergen‐specific immunotherapy for pre‐seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild‐to‐moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l‐tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). Previous non‐clinical safety testing, including rat repeat dose toxicity in adult and juvenile animals, rat reproductive toxicity and rabbit local tolerance studies showed no safety findings of concern. A new Good Laboratory Practice compliant rat subcutaneous repeat dose toxicity study to evaluate a higher clinical dose and modified posology (once every 2 weeks for 13 weeks) showed no signs of toxicity. As seen in previous studies, relatively minor, immunostimulatory effects were seen such as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased A/G ratio) and increased fibrinogen as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL and/or the presence of l‐tyrosine within the adjuvanted vaccine. This new toxicity study with PQ Grass therefore supports longer posology with higher dose levels.

show abstract

Dose site reactions and related findings after vaccine administration in safety studies

Cited by 37 publications

References 26 publications

Preclinical safety and immunological efficacy of Alternaria alternata polymerized extracts

Preclinical safety and immunological efficacy of Alternaria alternata polymerized extracts

A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques

New toxicity testing of PQ grass allergy immunotherapy to support product development

Contact Info

Product

Resources

About