Use of lentiviral vectors in vaccination

Ku, Min-Wen; Charneau, Pierre; Majlessi, Laleh

doi:10.1080/14760584.2021.1988854

Cited by 21 publications

(43 citation statements)

References 157 publications

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“…Second, because HIV-1-based lentiviral vectors can transduce nondividing cells, they can be applied to broad target cells including neural cells and macrophages. In particular, lentiviral vectors can transduce dendritic cells, leading to the e cient induction of both humoral and cellular immunity to antigens [32]. Therefore, veterinary and agricultural elds might require the application of HIV-1-based lentiviral vectors.…”

Section: Discussionmentioning

confidence: 99%

Generation of a bovine cell line for gene engineering using an HIV-1-based lentiviral vector

Morizako

Butlertanaka

Tanaka

et al. 2022

Preprint

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Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors are indispensable tools for gene engineering in mammalian cells. Conversely, lentiviral vector transduction is severely inhibited in bovine cells. Previous studies demonstrated that this inhibition is caused by the anti-lentiviral host factor tripartite motif containing 5 (TRIM5), which targets incoming HIV-1 virions by interacting with the viral capsid. In this study, we investigated several methods for overcoming the limited applicability of lentiviral vectors in bovine cells. First, we demonstrated that the SPRY domain of bovine TRIM5 is the major determinant of anti-viral activity. Second, we found that mutations that allow the capsid to evade rhesus macaque TRIM5α minimally rescued HIV-1 infectivity in bovine-derived MDBK cells. Third, we found that cyclosporine A, which relieves the inhibition of HIV-1 infection in monkey cells, significantly rescued the impaired HIV-1 infectivity in MDBK cells. Lastly, we successfully generated a bovine cell line lacking intact TRIM5 using the CRISPR/Cas9 technique. This TRIM5 knockout cell line displayed significantly higher susceptibility to an HIV-1-based lentiviral vector. In conclusion, our findings provide a promising gene engineering strategy for bovine cells, thereby contributing to innovations in agriculture and improvements in animal health.

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Section: Discussionmentioning

confidence: 99%

Generation of a bovine cell line for gene engineering using an HIV-1-based lentiviral vector

Morizako

Butlertanaka

Tanaka

et al. 2022

Preprint

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“…To introduce the K 986 P-V 987 P “2P”double mutation in S D614G or S Beta , a directed mutagenesis was performed by use of Takara In-Fusion kit on the corresponding pFlap plasmids. Various pFlap-ieCMV-S-WPREm or pFlap-ieCMV-S2P-WPREm plasmids were amplified and used to produce non-integrative vaccinal LV, as described elsewhere [2,6].…”

Section: Methodsmentioning

confidence: 99%

“…The resulting endogenous antigen expression in these cells, with unique ability of dendritic cells to activate naïve T cells [7], correlate with a strong ability of LVs at inducing high-quality effector and memory T cells [8]. Importantly, VSV-G pseudo-typing also avoids LVs to be targets of preexisting vector-specific immunity in humans which is key in vaccine development [5,6]. The safety of LV has been established in humans in a phase I/IIa Human Immunodeficiency Virus-1 therapeutic vaccine trial, even though if an integrative version of LV had been used in that clinical trial [9].…”

Section: Introductionmentioning

confidence: 99%

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An intranasal lentiviral booster broadens immune recognition of SARS-CoV-2 variants and reinforces the waning mRNA vaccine-induced immunity that it targets to lung mucosa

Vesin

Lopez

Noirat

et al. 2022

Preprint

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As the COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines wains and needs to be strengthened and broadened in specificity. Vaccination by the nasal route induces mucosal humoral and cellular immunity at the entry point of SARS-CoV-2 into the host organism and has been shown to be the most effective for reducing viral transmission. The lentiviral vaccination vector (LV) is particularly suitable for this route of immunization because it is non-cytopathic, non-replicative and scarcely inflammatory. Here, to set up an optimized cross-protective intranasal booster against COVID-19, we generated an LV encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::SBeta-2P). mRNA vaccine primed and -boosted mice, with waning primary humoral immunity at 4 months post-vaccination, were boosted intranasally with LV::SBeta-2P. Strong boost effect was detected on cross-sero-neutralizing activity and systemic T-cell immunity. In addition, mucosal anti-Spike IgG and IgA and lung resident B cells, effector memory and resident T cells were productively induced, correlating with complete pulmonary protection against the SARS-CoV-2 Delta variant, demonstrating the suitability of the LV::SBeta-2P vaccine candidate as an intranasal booster against COVID-19.

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“…Apart from pathogens, immunization against cancer using integrative LV has been implemented and shown to have comparable production of cancer specific immune cells to the commonly used adenoviral vector, as well as having more efficient expressions, and better quality of immune cells production due to little-to-no pre-existing antibodies towards lentiviral vector in human bodies ( Ku et al, 2021b ). Ku, Charneau & Majlessi (2021) had also previously reviewed in the context of vaccination using integrating LV. Nonetheless, applications of IDLV for cancer vaccination have also been studied actively.…”

Section: Applications Of Idlv For Clinical Implementationsmentioning

confidence: 99%

Integrase deficient lentiviral vector: prospects for safe clinical applications

Yew

Gurumoorthy

Nordin

et al. 2022

PeerJ

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HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector’s replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.

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Use of lentiviral vectors in vaccination

Cited by 21 publications

References 157 publications

Generation of a bovine cell line for gene engineering using an HIV-1-based lentiviral vector

Generation of a bovine cell line for gene engineering using an HIV-1-based lentiviral vector

An intranasal lentiviral booster broadens immune recognition of SARS-CoV-2 variants and reinforces the waning mRNA vaccine-induced immunity that it targets to lung mucosa

Integrase deficient lentiviral vector: prospects for safe clinical applications

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