The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A

Agnolon, Valentina; Bruno, Cristina; Leuzzi, Rosanna; Galletti, Bruno; D’Oro, Ugo; Pizza, Mariagrazia; Seubert, Anja; O’Hagan, Derek T.; Baudner, Barbara C.

doi:10.1016/j.ijpharm.2015.06.030

Cited by 13 publications

(8 citation statements)

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“…29,65 Consistent with prior studies, MF59 induced higher binding titers than alum alone. 46,[83][84][85] However, addition of the TLR4 and 7 agonists only improved antibody titers when formulated with alum and not ANE, which correlated with higher TLR-specific gene activation ( Figure 3G-H). One explanation for this is that ANE incorporates the TLR agonists into the oil phase, which may be less effective retaining the TLR agonists compared with alum adsorption.…”

Section: Discussionmentioning

confidence: 97%

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

et al. 2017

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Section: Discussionmentioning

confidence: 97%

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

et al. 2017

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“…Alum-TLR7a is a proprietary GSK adjuvant in development, made by adsorption of the TLR7 agonist SMIP7.10 to alum [16].…”

Section: Antigens and Adjuvantsmentioning

confidence: 99%

“…Total IgG titres against all vaccine antigens were analysed by Luminex penta-plex immunoassay as described elsewhere [16]. Titres are expressed as Relative Luminex Units per ml (RLU/ml), resulting from conversion of the registered median fluorescence intensities (MFI) through hyper-immune reference antisera.…”

Section: Luminex Immunoassaymentioning

confidence: 99%

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Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

Misiak

Leuzzi

Allen

et al. 2017

Vaccine

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a b s t r a c tA resurgence of whooping cough (pertussis) has been observed in recent years in a number of developed countries, despite widespread vaccine coverage. Although the exact reasons of the recurrence of pertussis are not clear, there are a number of potential causes, like antigenic variation in the circulating strains of Bordetella pertussis, changes in surveillance and diagnostic tools, and potential differences in protection afforded by current acellular pertussis (aP) vaccines compared to more reactogenic whole cell (wP) vaccines, which they replaced. Studies in animal models have shown that induction of cellular as well as humoral immune responses are key to conferring effective and long lasting protection against B. pertussis. wP vaccines induce robust Th1/Th17 responses, which are associated with good protection against lung infection. In contrast, aP vaccines induce mixed Th2/Th17 responses. One research option is to modify current aP vaccines with the intention of inducing protective T cell responses, without compromising on their low reactogenicity profile. Here we found that formulation of an aP vaccine with a novel adjuvant based on a Toll-like receptor 7 agonist (TLR7a) adsorbed to aluminum hydroxide (alum) enhanced B. pertussis-specific Th1 and Th17 responses and serum IgG2a/b antibodies, which had greater functional capacity than those induced by aP formulated with alum alone. Furthermore, addition of a TLR7a enhanced the protective efficacy of the aP vaccine against B. pertussis aerosol challenge; protection was comparable to that of a wP vaccine. These findings suggest that alum-TLR7a is a promising adjuvant for clinical development of next generation pertussis vaccines.

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“…In contrast to early vaccines which utilized inactivated whole organisms or attenuated live vaccines [ 8 , 9 ], there is an increasing emphasis in contemporary vaccines on the use of subunit vaccines which have the distinct advantages of ease of production, quality control, and safety; however, such subunit antigens are largely soluble proteins and tend to be poorly immunogenic, necessitating the use of adjuvants to induce robust immune responses. The Food and Drug Administration (FDA) defines adjuvants as “agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen.” The addition of adjuvants can enhance vaccine effectiveness, especially for poorly immunogenic antigens, and may be of particular value in pediatric and geriatric populations, and in the immunocompromised [ 10 – 15 ]. Currently, the only vaccine adjuvants approved by the FDA are 'alum' (amorphous aluminum hydroxyphosphate sulfate) [ 16 ], introduced by Glenny in 1926 [ 17 ] and 3'- O -desacyl-4′-monophosphoryl lipid A, (MPLA), a Toll-like receptor 4 (TLR4) agonist derived from limited hydrolysis of Re-type lipopolysaccharide isolated from Salmonella minnesota Re595 [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen

et al. 2016

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Small-molecule agonists have been identified for TLR7, TLR8, TLR4 and TLR2 thus far, and chemotypes other than those of canonical ligands are yet to be explored for a number of innate immune receptors. The discovery of novel immunostimulatory molecules would enhance the repertoire of tools available for interrogating innate immune effector mechanisms, and provide additional venues for vaccine adjuvant development. A multiplexed, reporter gene-based high-throughput assay capable of detecting agonists of TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, NOD1 and NOD2 was utilized in screening 123,943 compounds, in which amphotericin B (AmpB) and nystatin were identified as prominent hits. The polyene antifungal agents act as TLR2- and TLR4-agonists. The TLR4-stimulatory activity of AmpB was similar to that of monophosphoryl lipid A, suggestive of TRIF-biased signaling. The adjuvantic activity of AmpB, at a dose of 100 micrograms, was comparable to several other candidate adjuvants in rabbit models of immunization. These results point to its potential applicability as a safe and effective adjuvant for human vaccines.

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The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A

Cited by 13 publications

References 54 publications

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen

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