Immunization delivered by lentiviral vectors for cancer and infectious diseases

Hu, Biliang; Tai, April; Wang, Pin

doi:10.1111/j.1600-065x.2010.00967.x

Cited by 81 publications

(84 citation statements)

References 190 publications

(341 reference statements)

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“…WT or engineered VSV has been shown to be efficacious in preclinical models against malignant glioma, melanoma, hepatocellular carcinoma, breast adenocarcinoma, selected leukemias, prostate cancer-based tumors, osteosarcoma, and others (10)(11)(12)(13)(14). The attributes of VSV-G have also been used to develop VSV-based vaccination protocols for tumor antigens, as well as for a range of pathogens (15), including influenza (1) and HIV, for which experiments with monkeys showed a great deal of promise (4,16). Recently, recombinant VSV-based vaccination against tumor antigens was shown to cure established tumors (17).…”

mentioning

confidence: 99%

LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus

Finkelshtein

Werman

Novick

et al. 2013

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

503

398

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Vesicular stomatitis virus (VSV) exhibits a remarkably robust and pantropic infectivity, mediated by its coat protein, VSV-G. Using this property, recombinant forms of VSV and VSV-G-pseudotyped viral vectors are being developed for gene therapy, vaccination, and viral oncolysis and are extensively used for gene transduction in vivo and in vitro. The broad tropism of VSV suggests that it enters cells through a highly ubiquitous receptor, whose identity has so far remained elusive. Here we show that the LDL receptor (LDLR) serves as the major entry port of VSV and of VSV-G-pseudotyped lentiviral vectors in human and mouse cells, whereas other LDLR family members serve as alternative receptors. The widespread expression of LDLR family members accounts for the pantropism of VSV and for the broad applicability of VSV-G-pseudotyped viral vectors for gene transduction.

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mentioning

confidence: 99%

LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus

Finkelshtein

Werman

Novick

et al. 2013

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

503

398

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“…Among novel strategies, delivery of the immunogens by lentiviral vectors proved particularly effective to vaccinate against infectious diseases and cancer (26,31,37,48). Compared to vectors derived from other viruses, those derived from lentiviruses offer advantages such as low or null preexisting population immunity, ability to transport one or more heterologous genes (transgenes), delivery of the transgenes to replicating and quiescent cells (trans-duction), and prolonged transgene expression.…”

mentioning

confidence: 99%

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

Chiuppesi

Vannucci

Luca

et al. 2012

J Virol

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Genital herpes is caused by herpes simplex virus 1 (HSV-1) and HSV-2, and its incidence is constantly increasing in the human population. Regardless of the clinical manifestation, HSV-1 and HSV-2 infections are highly transmissible to sexual partners and enhance susceptibility to other sexually transmitted infections. An effective vaccine is not yet available. Here, HSV-1 glycoprotein B (gB1) was delivered by a feline immunodeficiency virus (FIV) vector and tested against HSV-1 and HSV-2 vaginal challenges in C57BL/6 mice. The gB1 vaccine elicited cross-neutralizing antibodies and cell-mediated responses that protected 100 and 75% animals from HSV-1- and HSV-2-associated severe disease, respectively. Two of the eight fully protected vaccinees underwent subclinical HSV-2 infection, as demonstrated by deep immunosuppression and other analyses. Finally, vaccination prevented death in 83% of the animals challenged with a HSV-2 dose that killed 78 and 100% naive and mock-vaccinated controls, respectively. Since this FIV vector can accommodate two or more HSV immunogens, this vaccine has ample potential for improvement and may become a candidate for the development of a truly effective vaccine against genital herpes.

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“…Numerous animal studies have proven the efficiency and safety of lentivectors (LVs) as vaccination moieties (6,7). As lentivectors are intrinsically immunogenic, they deliver both antigens and activation signals to antigen-presenting cells (8).…”

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confidence: 99%

Targeting of Human Antigen-Presenting Cell Subsets

Goyvaerts

Dingemans

Groeve

et al. 2013

J Virol

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dAntigen-presenting cells are a heterogeneous group of cells that are characterized by their functional specialization. Consequently, targeting specific antigen-presenting cell subsets offers opportunities to induce distinct T cell responses. Here we report on the generation and use of nanobodies (Nbs) to target lentivectors specifically to human lymph node-resident myeloid dendritic cells, demonstrating that Nbs represent a powerful tool to redirect lentivectors to human antigen-presenting cell subsets. Since the discovery of dendritic cells (DCs) in 1973, these antigen-presenting cells have been at the center of attention in vaccine development (1). In the past decade, an extra dimension of complexity was introduced by revealing an unforeseen diversity of DC subsets with distinct functions and locations (2-4). Since DC subsets induce distinct immune responses, it might be beneficial to develop strategies to target particular DC subsets and as such exploit the immune system to its full potential (5).Numerous animal studies have proven the efficiency and safety of lentivectors (LVs) as vaccination moieties (6, 7). As lentivectors are intrinsically immunogenic, they deliver both antigens and activation signals to antigen-presenting cells (8). Furthermore, the lentivectors' envelopes are well suited for engineering, enabling the design of targeted lentivectors. Several methods have been described to redirect lentivectors to specific antigen-presenting cells (9-12). However, to our knowledge subset-specific delivery of transgenes has not been described.Targeting myeloid DCs could be advantageous as they are considered to be important mediators of antigen-specific immunity. They are able to induce proper and oriented stimulation of CD4 ϩ T helper 1 and CD8 ϩ cytotoxic T cells. In addition, targeting may reduce the risk of adverse reactions such as autoimmune responses or induction of tolerance due to transgene expression and presentation by non-antigen-presenting cells or tolerogenic DC subtypes. Finally, as myeloid DCs have a limited life span, their targeting should result in a natural clearance of the lentivector and as such in a reduction of the risk of insertional mutagenesis.We recently delivered a proof of concept on the use of nanobodies (Nbs) to target lentivectors to antigen-presenting cells (10). Nbs or V H H fragments are antibody fragments of about 12 to 25 kDa that are engineered from heavy-chain-only antibodies found in Camelidae. Because of their size and target affinity, they are of particular interest as targeting moieties. In the present study, we further refined the transduction profile of lentivectors, targeting them to human myeloid DCs using Nbs.Two Nb libraries, derived from peripheral blood lymphocytes of llamas that were immunized with immature or lipopolysaccharide-stimulated murine bone marrow-derived DCs, were at our disposal (13). These were screened for cross-reactivity with hu-

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Immunization delivered by lentiviral vectors for cancer and infectious diseases

Cited by 81 publications

References 190 publications

LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus

LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

Targeting of Human Antigen-Presenting Cell Subsets

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