Emulsion-based adjuvants for influenza vaccines

Abstract

The ongoing epizootic of highly pathogenic avian H5N1 influenza and its direct transmissibility and high pathogenicity in humans has led to renewed interest in the development of influenza vaccines with enhanced immunogenicity. Influenza vaccines are currently under development against influenza strains that are potentially pandemic threats, such as H5N1, as well as against the current seasonal influenza strains for use in populations susceptible to severe influenza disease. Influenza vaccines may be generally divided into two types: seasonal vaccines for use in a population that is largely primed to subtypes of the circulating influenza A strains and pandemic influenza vaccines that are designed to protect against influenza A viruses of a hemagglutinin (HA) subtype, to which the vast majority of the population is immunologically naive. Pandemic influenza vaccines can be further subdivided into prepandemic vaccines produced for use prior to or just after the declaration of a pandemic, and pandemic influenza vaccines that would be produced and used only after a pandemic is declared. Prepandemic influenza vaccines are formulated using HA and neuraminidase, which are likely to be antigenically similar to the influenza virus subtype deemed to pose the most probable pandemic threat. Enhanced vaccine immunogenicity is desirable for pandemic influenza vaccines and for seasonal vaccines used in target populations, such as the elderly, in which vaccine responses against the circulating influenza subtypes may be weak. Various methods to enhance the immunogenicity of influenza vaccines are under evaluation. Along with dose escalation and alternative delivery routes, strategies for improving the immunogenicity of influenza vaccines have focused on the use of immunologic adjuvants. An adjuvanted seasonal influenza vaccine, Fluad, has been licensed in some countries in Europe since 1997 for the elderly population, and a number of clinical trials have been completed or are in progress evaluating the use of adjuvants with pandemic and seasonal influenza vaccines. This review will focus on the use of emulsion-based adjuvants for enhancing the immunogenicity of pandemic influenza vaccines and of seasonal influenza vaccines in target populations.

Effect of biosecurity measures and early detection systems, mitigation measures and surveillance strategies on the spread of HPAI and LPAI between farms

“…The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. (Vahlenkamp et al, 2008) (Vasileiou et al, 2008) Study population (Veits et al, 2006) Not relevant outcomes (Vela et al, 2012) Not relevant outcomes (Velumani et al, 2008) Not relevant outcomes (Vergara-Alert et al, 2011) Not relevant outcomes (Vesikari et al, 2012) Study population (Vieira et al, 2009) Territory (Vivancos et al, 2011a) Study population (Vivancos et al, 2011b) Study population (Voeten et al, 2009) Not relevant outcomes (Vogel et al, 2009) Study population (Walker et al, 2010) Territory (Walker et al, 2012) Territory (H. Study population (Wan, 2012) Territory (X.-F. ) Territory Study population Territory ) Territory Not relevant outcomes Not relevant outcomes (Werner and Harder, 2006) Language (Whiteley et al, 2007) Study population (Wilson et al, 2013) Territory (Wu et al, 2006) Study population (Wu et al, 2015) Territory Not relevant outcomes (Xing et al, 2008) Not relevant outcomes (Yalcin et al, 2010) Not relevant outcomes (Yamaguchi et al, 2010) Territory Territory (Yang et al, 2012) Study population (Yang et al, 2007) Study population (Yassine et al, 2013) Study population The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure.…”

Applications of nanomaterials as vaccine adjuvants

“…12,13,21,22,[44][45][46]50,51 Their nanoscale size, with all three dimensions ranging from 0.1 to 100 nm, happens to be the size range of the fundamental building blocks of biology (including DNA, proteins, viruses, ultrastructures and organelles). Thus, the ways in which engineered nanomaterials may interfere with the function of the host immune system and how these immunomodulatory activities may affect vaccines are increasingly important questions.…”

“…In particular, MF59 has shown more potent adjuvant activity than alum in inducing humoral and T helper type 1 (Th1) immune responses. 21,22 Other nano-adjuvants, including virus-like nanoparticles (VLNs) (15-30 nm), poly(lactide-co-glycolide) (PLGA) nanoparticles (100-200 nm), cationic liposomes, nanoemulsion W 805 EC (400 nm), and cholesterol-bearing nanogel (30-40 nm), are under investigation in clinical trials nearing completion. 11 Emerging evidence shows that the ability to engineer and integrate desired properties and functions into nanomaterials will significantly contribute to generating novel adjuvants.…”

“…In addition to their delivery function, a great number of nanoparticles have shown immunomodulatory effects, particularly for innate immune signaling. For example, nanoparticles can induce inflammasome activation in macrophages and DCs, [44][45][46] enhance antigen presentation and APC maturation, 33,34 recruit immune cells, 21,22,47,48 direct T cell differentiation to a particular subtype, and activate the complement system. 12,13,[49][50][51] Therefore, nanomaterials constitute a multifunctional unit to integrate target delivery and immunomodulation effects for clinical use in vaccination.…”

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

“…Therefore, many studies have focused on increasing the immunogenicity of M2-and HA2-based vaccines with various vaccine adjuvants (10). Although several hundred different adjuvants have been tested for use in novel vaccine design during the last few decades, the vast majority have not been successfully approved for human use, with limitations including lack of efficacy, unacceptable local or systemic toxicity, difficulty of manufacturing, poor stability, and prohibitive cost (10)(11)(12)(13). For this reason, until recently, aluminum-based mineral salts have been the most widely used adjuvant in human vaccines.…”