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O'Hagan D.T.,Novartis | Fox C.B.,IDRI
Vaccine | Year: 2015

Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. © 2015 Elsevier Ltd. Source

Bolz M.,Swiss Tropical and Public Health Institute | Bolz M.,University of Basel | Benard A.,Swiss Tropical and Public Health Institute | Benard A.,University of Basel | And 13 more authors.
PLoS Neglected Tropical Diseases | Year: 2016

Background: Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a chronic ulcerative neglected tropical disease of the skin and subcutaneous tissue that is most prevalent in West African countries. M. ulcerans produces a cytotoxic macrolide exotoxin called mycolactone, which causes extensive necrosis of infected subcutaneous tissue and the development of characteristic ulcerative lesions with undermined edges. While cellular immune responses are expected to play a key role against early intracellular stages of M. ulcerans in macrophages, antibody mediated protection might be of major relevance against advanced stages, where bacilli are predominantly found as extracellular clusters. Methodology/Principal Findings: To assess whether vaccine induced antibodies against surface antigens of M. ulcerans can protect against Buruli ulcer we formulated two surface vaccine candidate antigens, MUL_2232 and MUL_3720, as recombinant proteins with the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion. The candidate vaccines elicited strong antibody responses without a strong bias towards a TH1 type cellular response, as indicated by the IgG2a to IgG1 ratio. Despite the cross-reactivity of the induced antibodies with the native antigens, no significant protection was observed against progression of an experimental M. ulcerans infection in a mouse footpad challenge model. Conclusions: Even though vaccine-induced antibodies have the potential to opsonise the extracellular bacilli they do not have a protective effect since infiltrating phagocytes might be killed by mycolactone before reaching the bacteria, as indicated by lack of viable infiltrates in the necrotic infection foci. © 2016 Bolz et al. Source

O'Hagan D.T.,Novartis | Tsai T.,Novartis | Reed S.,IDRI
Birkhauser Advances in Infectious Diseases | Year: 2011

Emulsions have a long history of use as potent and effective adjuvants in humans for a range of vaccines, particularly for influenza. Although older mineral oil- and water-in-oil-based emulsion adjuvants did not have an overall safety and tolerability profile to allow them to be acceptable for widespread use, a newer generation of oil-in-water adjuvants has been recently developed, based on the use of the biodegradable oil squalene. These adjuvants have shown particular value in the development of new generation vaccines to offer enhanced protection against both seasonal and pandemic strains of influenza virus. The first oil-in-water emulsion adjuvant included in an approved flu vaccine was MF59, which was originally licensed in Europe in 1997 as an improved influenza vaccine for the elderly. In the very recent past, MF59 and related adjuvants have shown their value by offering the possibility of significant antigen dose reductions and higher potency products in the face of the H1N1 pandemic emergency and other pandemic threats. The recent H1N1 global problem allowed the opportunity for widespread use of emulsionbased adjuvants in a range of population groups in a number of countries, in which strict monitoring of safety was the norm. Importantly, this widespread use allowed the safety profile of squalene-based emulsion adjuvants to be further substantiated in large and diverse populations of humans, including young children and pregnant women. It is our confident prediction that the coming years will see wider use and further licensures for oil-in-water emulsion adjuvants, particularly for improved flu vaccines. © Springer Basel AG 2011. Source

The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cellinducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted. © 2013 Landes Bioscience. Source

Fox C.B.,IDRI | Haensler J.,Sanofi S.A.
Expert Review of Vaccines | Year: 2013

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles. © 2013 Informa UK Ltd. Source

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