Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

Ghobadloo, Shahrokh M.; Balcerzak, Anna K.; Gargaun, Ana; Muharemagic, Darija; Mironov, Gleb G.; Capicciotti, Chantelle J.; Briard, Jennie G.; Ben, Robert N.; Berezovski, Maxim V.

doi:10.1038/srep05903

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…A few IRI-active but TH-defective compounds were discovered, which were further investigated for cryopreservation purposes. 135 , 136 C-linked AFGP analogues with either too short, or too long linkers, 134 or with glucose, mannose, or talose instead of galactose were (virtually) IRI inactive. 131 This led to the proposal of a link between IRI activity and carbohydrate hydration.…”

Section: Synthetic Analogues Of Ice-binding Proteinsmentioning

confidence: 99%

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From ice-binding proteins to bio-inspired antifreeze materials

2017

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Ice-binding proteins (IBP) facilitate survival under extreme conditions in diverse life forms. Successful translation of this natural cryoprotective ability into man-made materials would open up new avenues in biomedicine, agrifood and materials science. This review covers recent advances in the field of IBPs and their synthetic analogues, focusing on fundamental insights of biological and technological relevance.

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Section: Synthetic Analogues Of Ice-binding Proteinsmentioning

confidence: 99%

“… 148 The hydrogelator N -octyl- d -gluconamide increased the infectivity and thermostability of candidate viral vectors for cancer vaccine development from vaccinia virus (VV) and herpes simplex virus type 1 (HSV-1), and furthermore improves the recovery of cryopreserved vesicular stomatitis virus (VSV). 136 …”

Section: Applicationsmentioning

confidence: 99%

From ice-binding proteins to bio-inspired antifreeze materials

2017

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“…Several agents have been employed to increase the low temperature stability of viruses as effective vaccines such as metal ions, albumin, and gelatin. − However, none of these compounds have provided satisfactory results for oncolytic viruses due to low cryoprotection potency or high cell toxicity. The stabilizing effect of glycoproteins on the VSV surface inspired us to look at VSV-specific aptamers. The goal of this study was to determine whether aptamers can preserve the infectivity of VSV after multiple freeze–thaw cycles and in the presence of nAbs (Scheme ).…”

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confidence: 99%

Aptamer-Facilitated Cryoprotection of Viruses

Ghobadloo

Gargaun

Casselman

et al. 2014

ACS Med. Chem. Lett.

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Global vaccination and gene therapy programs have an urgent demand for stabilization of viral vectors at low temperature. We used a quadramer, a bridge-connected DNA tetra-aptamer to antivesicular stomatitis virus (VSV), as a viral cryoprotectant. Results showed that the tetravalent antivirus DNA aptamers protect viral activity during multiple freeze− thaw cycles, shield from neutralizing antibodies, and decrease aggregation of viral particles.KEYWORDS: Aptamer, quadramer, vesicular stomatitis virus, viral stabilizers, cryoprotection C ryoprotection of viral vectors is essential for the development of vaccines and anticancer therapeutics. Because of temperature sensitivity, many viruses should be stored frozen. 1 Therefore, delivery of active viruses depends on a cold chain, a distribution network set up to maintain optimal low temperatures during the transportation and storage. However, this cold chain system represents a major economic and logistical burden, estimated to be as high as 80% of the entire financial cost. 2 In addition, a viral vector should be infectious in the presence of a host's neutralizing antibodies (nAbs). In the work, we used vesicular stomatitis virus (VSV) as an important viral vector in targeted oncolytic immunotherapies. 3 It is an enveloped RNA rhabdovirus that consists of a lipid envelope enclosing a nucleocapsid and an associated matrix formed by M proteins. 4−6 VSV is innocuous and engineered to target malignant cells and also increase a tumor's susceptibility to chemotherapeutic agents and the host immune response. Furthermore, VSV is a suitable choice for vaccine vectors and also has a key role in immunity and virology research. One of the challenges of utilizing VSV is its limited stability under different handling and storage conditions. 7 Several agents have been employed to increase the low temperature stability of viruses as effective vaccines such as metal ions, albumin, and gelatin. 8−11 However, none of these compounds have provided satisfactory results for oncolytic viruses due to low cryoprotection potency or high cell toxicity. The stabilizing effect of glycoproteins on the VSV surface 12 inspired us to look at VSV-specific aptamers. The goal of this study was to determine whether aptamers can preserve the infectivity of VSV after multiple freeze−thaw cycles and in the presence of nAbs (Scheme 1).Results and Discussion. We used anti-VSV DNA aptamer clones Z23, Z29, S39, and M50 (Table 1) that were previously selected in our laboratory and have shown high affinity to VSV. 13 To increase avidity and serum stability, we designed a quadramer, which was made by connecting four aptamers (equimolar mixture of all above-mentioned aptamers), with an oligonucleotide bridge (Figure 1 and Scheme 1). We measured the apparent dissociation constant (K d ) for monomeric pool and quadramer using the approach described by Sefah et al. 14 The K d for monomeric pool of four clones was 71 ± 15 nM, and quadramer had affinity of 22 ± 9 nM. The protective role of the aptamers and q...

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Viral vectors as vaccine platforms: from immunogenicity to impact

Ewer

Lambe

Rollier

et al. 2016

Current Opinion in Immunology

144

122

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Viral vectors are the vaccine platform of choice for many pathogens that have thwarted efforts towards control using conventional vaccine approaches. Although the STEP trial encumbered development of recombinant human adenovirus vectors only a few years ago, replication-deficient simian adenoviruses have since emerged as a crucial component of clinically effective prime-boost regimens. The vectors discussed here elicit functionally relevant cellular and humoral immune responses, at extremes of age and in diverse populations. The recent Ebola virus outbreak highlighted the utility of viral vectored vaccines in facilitating a rapid response to public health emergencies. Meanwhile, technological advances in manufacturing to support scale-up of viral vectored vaccines have helped to consolidate their position as a leading approach to tackling 'old' and emerging infections.

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Carbohydrate-Based Ice Recrystallization Inhibitors Increase Infectivity and Thermostability of Viral Vectors

Cited by 8 publications

References 35 publications

From ice-binding proteins to bio-inspired antifreeze materials

From ice-binding proteins to bio-inspired antifreeze materials

Aptamer-Facilitated Cryoprotection of Viruses

Viral vectors as vaccine platforms: from immunogenicity to impact

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