Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis

Ballester, Marie; Nembrini, Chiara; Dhar, Neeraj; Titta, Alexandre de; Piano, Cyntia De; Pasquier, Miriella; Simeoni, Eleonora; Vlies, André J. van der; McKinney, John D.; Hubbell, Jeffrey A.; Swartz, Melody A.

doi:10.1016/j.vaccine.2011.07.039

Cited by 111 publications

(69 citation statements)

References 30 publications

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“…Our 5′ end conjugation strategy between NP and CpG, which allows the latter to be released in the reductive endosomal environment, did not negatively influence the activity of the bound CpG, which were even more stimulatory when conjugated than their free counterparts. Free NPs have a very moderate adjuvant capacity on their own, as they only trigger a slight up-regulation of CD86 on the surface of DCs in vitro and no secretion of the proinflammatory cytokines IL-12p70, IL-6, and IL-1β (13). Moreover, by conjugating CpG to NPs, we could use a low dose of CpG to potently activate DCs in the LNs without substantially raising blood levels of the inflammatory cytokines TNF-α, IL-12p70, and IL-6 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Nanocarriers can be used to modulate the immune response induced by antigens and adjuvants by modifying their characteristics, such as stability, tissue and cell targeting, and DC-activating capacity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). We have previously described the targeting benefits of conjugating antigens to ultrasmall Pluronic-stabilized poly(propylene sulfide) (PPS) nanoparticles (NPs) in terms of CD8 + T-cell and Th1 responses (13,14). The hydrophobic PPS core is hydrolytically stable, allowing wet storage, yet is oxidized to products that are soluble in vivo (15,16).…”

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confidence: 99%

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Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Titta

Ballester

Julier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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232

218

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Significance High adjuvant doses are generally required to induce strong CD8 + T-cell immunity with subunit vaccines. Here we codeliver an antigen and an adjuvant coupled on separate ultrasmall polymeric nanoparticles. Because both payloads are attached to similarly sized nanoparticles, and as size is the principle determinant of nanoparticle drainage, this enhanced the dual uptake of antigen and adjuvant by cross-presenting dendritic cells resident in the draining lymph nodes. This cotargeting induced potent effector CD8 + T cells and a more powerful memory recall of these cytotoxic T cells compared with nanoparticle-conjugated antigen with free adjuvant. As such, nanoparticle conjugation enhanced the immunogenicity of adjuvants while maintaining a low dose, and thus limiting toxicity, affecting the design of future subunit vaccine formulations.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Titta

Ballester

Julier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

232

218

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“…[45] In a separate study, polypropylene sulfide nanoparticles conjugated with Ag85B antigen and adjuvant CpG were used to enhance vaccine delivery; in vivo results were also promising with mice demonstrating enhanced TB protection. [52] The role of nanoparticles as adjuvants to improve vaccine efficacy is certainly worth exploring. Some of the promising nanocarrier systems employed in TB vaccine development are further discussed below.…”

Section: Nanomaterials In Tb Vaccinesmentioning

confidence: 99%

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

Liang

Ding

et al. 2017

Adv Healthcare Materials

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worldwide was estimated at a staggering 10.4 million, with a significant percentage (10%) resulting from concomitant HIV-TB coinfections. [1] Given the closely knitted association between TB infections and poor sanitation/poverty, it thus comes with no surprise that an overwhelming majority of disease burden (60%) is actually shouldered by countries from the developing world (Figure 1). [1] TB infections are compounded by the emergence of multidrug resistance (MDR). In spite of the tremendous amount of resources and research dollars that have been devoted to TB research, TB diagnostics and treatment outcomes still remain startlingly poor. TB remains worryingly underreported, under-diagnosed and undertreated. A 4.3 million gap was reported between incident and notified TB cases, chiefly in developing countries; majority of TB infections remain latent and unreported, and only 30% of new incident TB cases were subjected to drug susceptibility testing. [1] The Xpert Mycobacterium Tuberculosis (MTB)/RIF assay remains the only available WHOrecommended rapid diagnostic platform for detection of TB and drug (rifampicin) resistance. Treatment success rates are highly variable, ranging from 28% (extensively drug-resistant strains) to 83% (garden strains) of TB. The rate of decline in TB incidence has remained stagnant at 1.5% annually over the past decade, far lagging behind the 5% projected by the WHO's End TB Strategy. Against such a backdrop, TB remains firmly entrenched among the top 10 causes of death worldwide. [2] To this end, the WHO has since 2015, adopted the End TB Strategy in an effort to stem this burgeoning epidemic. Major diagnostic and treatment gaps in TB management still remain, and these need to be addressed to effectively curtail TB spread and its impact on global health. Pathogenesis of TB InfectionsMTB is the infectious agent responsible for TB infections. It originates from the family Mycobacteriaceae and is an obligate bacteria chiefly spread via air droplets.

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“…In the following sections, the immunomodulatory activities of nanomaterials, including inflammasome activation, recruitment of immune cells and complement system activation, will be introduced. 12,13,21,22,33,34,[44][45][46][47][48][49][50][51][87][88][89][90] The potential mechanisms for these effects will also be discussed to facilitate an in-depth understanding of the inherent adjuvant activity of nanomaterials.…”

Section: Immunomodulatory Effects Of Nanomaterialsmentioning

confidence: 99%

“…12,[49][50][51]89,90 The degree of complement activation induced by nanomaterials is determined by their surface chemistry and size. Nanoparticles functionalized with different lipid-anchored gadolinium chelates were shown to induce rapid complement activation-dependent IgM antibody production and were propagated via the classical pathway.…”

Section: Complement Activationmentioning

confidence: 99%

Applications of nanomaterials as vaccine adjuvants

Zhu

Wang

Nie³

2014

Human Vaccines & Immunotherapeutics

127

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Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigenspecific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

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Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis

Cited by 111 publications

References 30 publications

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections

Applications of nanomaterials as vaccine adjuvants

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