Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants

Miyaji, Eliane N.; Carvalho, Eugénia; Oliveira, Maria Leonor S.; Raw, Isaı́as; Ho, Patricia

doi:10.1590/s0100-879x2011007500064

Cited by 32 publications

(26 citation statements)

References 18 publications

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“…The licensure of non-aluminum salt adjuvants took an additional 80 years (1). One reason for this long gap is that the principles of adjuvant activity were largely unknown; thus, the development of adjuvants was empirical, Moreover, many adjuvants, including Freund's adjuvant, were reactogenic and not acceptable for licensure (2). Recent methods to improve vaccine delivery have taken several approaches, including the use of virosomes (3)(4)(5), vector-based methods (6)(7)(8), liposome-based methods (9)(10)(11), and the use of more traditional formulation with adjuvants (12)(13)(14)(15)(16)(17).…”

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confidence: 99%

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Grenfell

Shollenberger

Samli

et al. 2015

Clin. Vaccine Immunol.

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bVaccination remains the most effective public health tool to prevent infectious diseases. Many vaccines are marginally effective and need enhancement for immunocompromised, elderly, and very young populations. To enhance immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new delivery method. VacSIM solution can easily be mixed with antigens, organisms, and adjuvants for injection. Postinjection, the peptides self-assemble into hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in the aqueous phase. We believe the depot provides slow release of immunogens, leading to increased activation of antigen-presenting cells that then drive enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type response following immunization with VacSIM, which was driven further toward Th1 with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2 environments, respectively. Restimulation of splenocytes suggests that VacSIM does not cause an immediate proinflammatory response in the host. Overall, these results suggest that VacSIM, as a new delivery method, has the potential to enhance immunogenicity and efficacy of numerous vaccines. Vaccines remain the single greatest public health tool to combat infectious diseases. Vaccine formulation and delivery are key to the ability of vaccines to induce the desired immune responses. One goal of vaccine delivery is to present vaccine antigens in a manner that enhances antigen-presenting-cell (APC) activation, leading to antigen/organism uptake and processing of vaccine antigen(s). Delivery methods or adjuvants that safely enhance vaccine immunogenicity/efficacy are desirable for vaccines that are marginally effective and for vaccines administered to low responders or immunocompromised populations. Additional goals are to reduce the number of doses required to induce effective, vaccine responses and to reduce the amount of vaccine/dose, especially when a single dose of vaccine is administered, as with annual influenza vaccines. Lastly, in pandemics, a vaccine that produces high titers after a single administration would be beneficial. Recent advances in the understanding of how innate mechanisms influence adaptive immunity have led to more rational design in the development of new vaccine adjuvants and delivery systems.Aluminum salts were the first adjuvants licensed for human vaccines in the 1920s. The licensure of non-aluminum salt adjuvants took an additional 80 years (1). One reason for this long gap is that the principles of adjuvant activit...

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confidence: 99%

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Grenfell

Shollenberger

Samli

et al. 2015

Clin. Vaccine Immunol.

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“…O sistema imune inato é considerado a primeira linha de defesa do hospedeiro dado a capacidade de induzir uma resposta rápida e menos específica quando em contato com agentes invasores (Miyaji et al 2011). O reconhecimento dos patógenos na imunidade inata é mediado pelos Receptores de Reconhecimento de Padrões (RRPs) (Juul-Madsen et al 2008).…”

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Seleção, caracterização e clonagem dos genes fljB e groEL agonistas dos receptores de reconhecimento de padrão do sistema imune inato das aves

et al. 2014

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Pesq. Vet. Bras. 34(0):000-000, oooo 2014 217 RESUMO.-A produção recombinante de agonistas dos receptores do reconhecimento de padrão do sistema imune inato tem fornecido uma nova ferramenta para a produção de imunoestimulantes para animais. O padrão molecular associado ao patógeno (PAMP), flagelina, codificado pelo gene fljB de Salmonella Typhimurium e o padrão molecular associado ao dano (DAMP) HSP60, codificado pelo gene groEL da S. Typhimurium e S. Enteritidis, são reconhecidos por receptores de reconhecimento de padrões (RRPs) do sistema imune inato das aves. No presente estudo, foi feita a clonagem de fragmentos genéticos dos genes fljB de S. Typhimurium e groEL de S. Typhimurium e S. Enteritidis inseridos no vetor de expressão pET100/D-TOPO e transformados em células de E. coli TOP10. Os clones foram avaliados pela PCR de colônia, PCR de DNA plasmidial e sequenciamento genômico para a confirmação da presença desses genes. Na PCR de colônia, foram identificadas em 80%, 60% e 80% das colônias transformadas, a presença dos genes groEL The recombinant production of innate immune system pattern recognition receptor agonists has provided a new tool for the production of immunostimulants for animals. The molecular pattern associated with the pathogen (PAMP), flagellin, coded by the fljB gene from Salmonella Typhimirium, and the molecular pattern associated to the damage (DAMP), HSP60, coded by the groEL gene from S. Typhimurium and S. Enteritidis, are recognized by pattern recognition receptors (PRRs) of the innate immune system of birds. In the present study, we performed the cloning of genetic fragments of the genes fljB, from S. Typhimurium, and groEL from S. Typhimurium and S. Enteritidis inserted in expression vector pET100/D-TOPO and transformed in E. coli TO10 cells. The clones were evaluated by colony PCR, plasmidial DNA PCR and genome sequencing in order to confirm the presence of these genes. In the colony PCR, we identified the presence of genes groEL (S. Enteritidis), groEL (S. Typhimurium) and fljB (S. Typhimurium) in 80%, 60% and 80% of the transformed colonies, respectively. The cloning system adopted allowed the production of HSP60 genetic fragment clones and flagellin of Salmonella strains, allowing the posterior use of these clones in gene expression trials, with the future potential of being used as non-specific immunostimulants for birds.INDEX TERMS: Recombinant protein, PAMP, flagellin, DAMP, HSP60, birds.

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“…7 As we shall see, they are potential targets for small molecule adjuvants. 8 Adjuvants potentiate immune responses, reducing the dosing requirements needed to induce protective immunity, particularly for weakly immunogenic subunit vaccines. Few adjuvants are licensed for human use.…”

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The Immune System as Drug Target

Flower

2013

Immunol Immunogenet Insights

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ABSTRACT:The immune system is perhaps the largest yet most diffuse and distributed somatic system in vertebrates. It plays vital roles in fighting infection and in the homeostatic control of chronic disease. As such, the immune system in both pathological and healthy states is a prime target for therapeutic interventions by drugs-both small-molecule and biologic. Comprising both the innate and adaptive immune systems, human immunity is awash with potential unexploited molecular targets. Key examples include the pattern recognition receptors of the innate immune system and the major histocompatibility complex of the adaptive immune system. Moreover, the immune system is also the source of many current and, hopefully, future drugs, of which the prime example is the monoclonal antibody, the most exciting and profitable type of present-day drug moiety. This brief review explores the identity and synergies of the hierarchy of drug targets represented by the human immune system, with particular emphasis on the emerging paradigm of systems pharmacology.

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Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants

Cited by 32 publications

References 18 publications

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Seleção, caracterização e clonagem dos genes fljB e groEL agonistas dos receptores de reconhecimento de padrão do sistema imune inato das aves

The Immune System as Drug Target

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