Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice

Ebensen, Thomas; Debarry, Jennifer; Pedersen, Gabriel Kristian; Błażejewska, Paulina; Weißmann, Sebastian; Schulze, Kai; McCullough, Kenneth C.; Cox, Rebecca Jane; Guzmán, Carlos A.

doi:10.3389/fimmu.2017.01223

Cited by 46 publications

(44 citation statements)

References 50 publications

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“…Interestingly, the adjuvantation of conventional influenza vaccines has also proven effective, not only for improving responsiveness in certain subpopulation groups [21], but also at broadening responsiveness to other influenza subtypes [22,23]. A critical aspect for the development of a vaccine conferring broad cross-protective immunity against influenza is the determination of vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

Next Generation Influenza Vaccines: Looking into the Crystal Ball

Guzmán¹

2020

Vaccines

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Influenza infections are responsible for significant number of deaths and overwhelming costs worldwide every year. Vaccination represents the only cost-efficient alternative to address this major problem in human health. However, current vaccines are fraught by many limitations, being far from optimal. Among them, the need to upgrade vaccines every year through a time-consuming process open to different caveats, and the critical fact that they exhibit poorer efficacy in individuals who are at high risk for severe infections. Where are we? How can knowledge and technologies contribute towards removing current roadblocks? What does the future offer in terms of next generation vaccines?

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Section: Discussionmentioning

confidence: 99%

Next Generation Influenza Vaccines: Looking into the Crystal Ball

Guzmán¹

2020

Vaccines

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“…Because HIV-1 replicates in various mucosal tissues, an HIV subunit vaccine allowing a prime/boost approach, combining two distinct mucosal sites, could more efficiently achieve a broader mucosal tissue coverage in both men and women. This explains the strong interest in developing various new galenic virosomal formulations under thermostable solid dosages for mucosal delivery, as early studies with liquid nasal 33,57 and sublingual (SL) 26,58 virosomes induced systemic and mucosal antibodies.…”

Section: Introductionmentioning

confidence: 99%

New GMP manufacturing processes to obtain thermostable HIV-1 gp41 virosomes under solid forms for various mucosal vaccination routes

Amacker¹,

Smardon

Mason³

et al. 2020

npj Vaccines

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The main objective of the MACIVIVA European consortium was to develop new Good Manufacturing Practice pilot lines for manufacturing thermostable vaccines with stabilized antigens on influenza virosomes as enveloped virus-like particles. The HIV-1 gp41-derived antigens anchored in the virosome membrane, along with the adjuvant 3M-052 (TLR7/8 agonist) on the same particle, served as a candidate vaccine for the proof of concept for establishing manufacturing processes, which can be directly applied or adapted to other virosomal vaccines or lipid-based particles. Heat spray-dried powders suitable for nasal or oral delivery, and freeze-dried sublingual tablets were successfully developed as solid dosage forms for mucosal vaccination. The antigenic properties of vaccinal antigens with key gp41 epitopes were maintained, preserving the original immunogenicity of the starting liquid form, and also when solid forms were exposed to high temperature (40°C) for up to 3 months, with minimal antigen and adjuvant content variation. Virosomes reconstituted from the powder forms remained as free particles with similar size, virosome uptake by antigen-presenting cells in vitro was comparable to virosomes from the liquid form, and the presence of excipients specific to each solid form did not prevent virosome transport to the draining lymph nodes of immunized mice. Virosome integrity was also preserved during exposure to <−15°C, mimicking accidental freezing conditions. These "ready to use and all-in-one" thermostable needle-free virosomal HIV-1 mucosal vaccines offer the advantage of simplified logistics with a lower dependence on the cold chain during shipments and distribution.

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“…CDG was the founding member of CDNs and showed excellent vaccine efficacy in infectious diseases and immunotherapy (16)(17)(18). Mechanistically, CDG adjuvanticity depends on stimulator of interferon genes (STING)-induced tumor necrosis factor (TNF) production in vivo (19,20) and is mediated by DCs (21).…”

Section: Introductionmentioning

confidence: 99%

New MoDC-Targeting TNF Fusion Proteins Enhance Cyclic Di-GMP Vaccine Adjuvanticity in Middle-Aged and Aged Mice

et al. 2020

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Cyclic dinucleotides (CDNs) are promising vaccine adjuvants inducing balanced, potent humoral, and cellular immune responses. How aging influences CDN efficacy is unclear. We examined the vaccine efficacy of 3 ′ ,5 ′-cyclic diguanylic acid (cyclic di-GMP, CDG), the founding member of CDNs, in 1-year-old (middle-aged) and 2-year-old (aged) C57BL/6J mice. We found that 1-and 2-year-old C57BL/6J mice are defective in CDG-induced memory T helper (Th)1 and Th17 responses and high-affinity serum immunoglobulin (Ig)G, mucosal IgA production. Next, we generated two novel tumor necrosis factor (TNF) fusion proteins that target soluble TNF (solTNF) and transmembrane TNF (tmTNF) to monocyte-derived dendritic cells (moDCs) to enhance CDG vaccine efficacy in 1-and 2-year-old mice. The moDC-targeting TNF fusion proteins restored CDG-induced memory Th1, Th17, and high-affinity IgG, IgA responses in the 1-and 2-year-old mice. Together, the data suggested that aging negatively impacts CDG vaccine adjuvanticity. MoDC-targeting TNF fusion proteins enhanced CDG adjuvanticity in the aging mice.

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Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice

Cited by 46 publications

References 50 publications

Next Generation Influenza Vaccines: Looking into the Crystal Ball

Next Generation Influenza Vaccines: Looking into the Crystal Ball

New GMP manufacturing processes to obtain thermostable HIV-1 gp41 virosomes under solid forms for various mucosal vaccination routes

New MoDC-Targeting TNF Fusion Proteins Enhance Cyclic Di-GMP Vaccine Adjuvanticity in Middle-Aged and Aged Mice

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