The perfect mix: recent progress in adjuvant research

Guy, Bruno

doi:10.1038/nrmicro1681

Cited by 533 publications

(395 citation statements)

References 130 publications

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“…We have developed a vaccine candidate fusion of 4 M. tuberculosis proteins (Rv1813, Rv2608, Rv3619, and Rv3620, belonging to the PE/PPE [proteins containing Pro-Glu/Pro-Pro-Glu motifs, respectively], EsX, and latency protein categories) (24), designated ID93. Protein antigens used in vaccines frequently result in low immunogenicity (25,26); thus, we elected to combine ID93 with a Toll-like receptor 4 (TLR4) agonist as an adjuvant.…”

Section: Et Al Have Shown a Transient Increase In Ifn-␥ From Cd4mentioning

confidence: 99%

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Baldwin

Reese

Huang

et al. 2016

Clin Vaccine Immunol

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dMycobacterium tuberculosis HN878 represents a virulent clinical strain from the W-Beijing family, which has been tested in small animal models in order to study its virulence and its induction of host immune responses following infection. This isolate causes death and extensive lung pathology in infected C57BL/6 mice, whereas lab-adapted strains, such as M. tuberculosis H37Rv, do not. The use of this clinically relevant isolate of M. tuberculosis increases the possibilities of assessing the long-lived efficacy of tuberculosis vaccines in a relatively inexpensive small animal model. This model will also allow for the use of knockout mouse strains to critically examine key immunological factors responsible for long-lived, vaccine-induced immunity in addition to vaccine-mediated prevention of pulmonary immunopathology. In this study, we show that the ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) tuberculosis vaccine candidate, currently in human clinical trials, is able to elicit protection against M. tuberculosis HN878 by reducing the bacterial burden in the lung and spleen and by preventing the extensive lung pathology induced by this pathogen in C57BL/6 mice.T he development of an effective Mycobacterium tuberculosis vaccine, and increased availability of novel drugs targeting drug-resistant strains, would significantly contribute to decreasing the continuing spread of this global disease. Nine million people were estimated to have contracted tuberculosis (TB) in 2013, with 1.5 million deaths occurring annually (1). Overall, 3.5% of new cases and 20.5% of previously treated cases are multidrugresistant (MDR) TB (1), although this can be as high as 35% and 75%, respectively, in central Asian countries. The Beijing lineage of TB has been associated with a number of MDR TB outbreaks (2-6) and accounts for approximately 13% of isolates worldwide (7). The Beijing lineage itself has expanded more rapidly than other lineages (8); this may be due to the higher virulence of modern strains compared with phylogenetically older sublineages (9-11). The clinical isolate, HN878, is a representative strain from the W-Beijing lineage. The HN878 isolate has been studied in mice to characterize the infectivity and pathogenicity of this virulent clinical strain of M. tuberculosis (12)(13)(14). These same studies have provided insight into the role of the immune response generated to this pathogen in animals and humans and how the immune response to HN878 contributes to the pathology induced following infection with this isolate. Mice infected with the hypervirulent HN878 strain have increased type I interferon (IFN) expression in the lung and decreased Th1 immunity (12), and HN878 infection in IFN-␣/␤R-deficient mice results in decreased bacterial growth (13). In humans, a type I IFN-␣ molecular signature, expressed by a population of isolated neutrophils, was observed in patients with active TB (15). More recently, analysis using a whole-genome microarray approach showed a similar type I interferon molecular signa...

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Section: Et Al Have Shown a Transient Increase In Ifn-␥ From Cd4mentioning

confidence: 99%

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Baldwin

Reese

Huang

et al. 2016

Clin Vaccine Immunol

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“…The immunogenicity of particulate materials seems to be negligible, since they are inert in stimulating innate immunity (4). In some cases, such as for poly(I·C), monophosphoryl lipid A (MPLA), and imidazoquinolines, particulate materials themselves have immunostimulatory activity to improve the immunogenicity of vaccines (23)(24)(25)(26)(27). However, it is sometimes difficult to control the formulation of these materials.…”

Section: Discussionmentioning

confidence: 99%

Induction of Potent Adaptive Immunity by the Novel Polyion Complex Nanoparticles

Uto

Akagi

Akashi

et al. 2015

Clin. Vaccine Immunol.

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The development of effective and simple methods of vaccine preparation is desired for the prophylaxis and treatment of a variety of infectious diseases and cancers. We have created novel polyion complex (PIC) nanoparticles (NPs) composed of amphiphilic anionic biodegradable poly(␥-glutamic acid) (␥-PGA) and cationic polymers as a vaccine adjuvant. PIC NPs can be prepared by mixing ␥-PGA-graft-L-phenylalanine ethylester (␥-PGA-Phe) polymer with cationic polymer in phosphate-buffered saline. We examined the efficacy of PIC NPs for antigen delivery and immunostimulatory activity in vitro and in vivo. PIC NPs enhanced the uptake of ovalbumin (OVA) by dendritic cells (DCs) and subsequently induced DC maturation. The immunization of mice with OVA-carrying PIC NPs induced potent and antigen-specific cellular and humoral immunity. Since PIC NPs can be created with water-soluble anionic ␥-PGA-Phe and a cationic polymer by simple mixing in the absence of any organic solvents, PIC NPs may have potential as a novel candidate for an effective antigen carrier and vaccine adjuvant. The induction of potent adaptive immunity is essential for an effective vaccine. Although using only a part of a pathogen, such as a purified protein component, is generally much safer than using the whole pathogen, such components can induce a modest humoral immune response but little or no cell-mediated immune response (1, 2). Removal or eradication of intracellular pathogens by the cell-mediated immune response is highly desired for the next generation of vaccines (3, 4). Several lines of evidence suggest that an appropriate adjuvant can strongly enhance the immunogenicity of antigens (5-7). Such adjuvants must be first recognized by the innate immune cells in order to induce adaptive immunity. Alum-based adjuvants (alum) that are approved for clinical use in humans can increase humoral immune responses without unacceptable side effects. However, they elicit cell-mediated immune responses only poorly (1, 5). Therefore, ideal adjuvants are expected to effectively induce not only humoral but also cell-mediated immune responses.Stimulation of the antigen-presenting cells (APCs) is considered to be important for the induction of adaptive immune responses (8, 9). Dendritic cells (DCs) are the most potent APCs that connect innate and adaptive immune responses (10). The interaction between antigens and DCs triggers the maturation of DCs in peripheral tissue. Immature DCs (iDCs) develop to mature DCs (mDCs) by interaction with various antigens, leading to the upregulation of costimulatory molecules and major histocompatibility complexes (MHCs). Subsequently, DCs migrate into the secondary lymphoid organs, present the processed antigen peptides to naive T cells, and induce adaptive immune responses. Thus, targeting selected antigens to DCs and subsequent stimulation of DCs constitute a pivotal strategy for establishing effective vaccine development.Particle-based adjuvants made from certain biomaterials have also been explored as an antigen carrier in vac...

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“…[32][33][34] The activation of Th cells will release a specific set of cytokines that modulate the B cell and CD8C CTL immune response, depending on the nature of the stimulant. 35 Th cell types Th-1, Th-2 or Th-17 will be induced accordingly. A Th-1 response develops in the presence of interleukin 12 (IL-12), which is in turn synthesized primarily by DCs and/or natural killer (NK) cells in the presence of bacteria or virus.…”

Section: Respiratory Epithelial Cellsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

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The perfect mix: recent progress in adjuvant research

Cited by 533 publications

References 130 publications

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Induction of Potent Adaptive Immunity by the Novel Polyion Complex Nanoparticles

Current prospects and future challenges for nasal vaccine delivery

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