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Article: Lentiviral Vectors as a Vaccine Platform against Infectious Diseases.

Nemirov, Kirill / Bourgine, Maryline / Anna, François / Wei, Yu / Charneau, Pierre / Majlessi, Laleh

2023 Volume 15, Issue 3

Abstract: Lentiviral vectors are among the most effective viral vectors for vaccination. In clear contrast to the reference adenoviral vectors, lentiviral vectors have a high potential for transducing dendritic cells in vivo. Within these cells, which are the most ...

Abstract	Lentiviral vectors are among the most effective viral vectors for vaccination. In clear contrast to the reference adenoviral vectors, lentiviral vectors have a high potential for transducing dendritic cells in vivo. Within these cells, which are the most efficient at activating naive T cells, lentiviral vectors induce endogenous expression of transgenic antigens that directly access antigen presentation pathways without the need for external antigen capture or cross-presentation. Lentiviral vectors induce strong, robust, and long-lasting humoral, CD8
Language	English
Publishing date	2023-03-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15030846
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Article ; Online: HLA-G Neo-Expression on Tumors.

Loustau, Maria / Anna, François / Dréan, Raphaelle / Lecomte, Martin / Langlade-Demoyen, Pierre / Caumartin, Julien

Frontiers in immunology

2020 Volume 11, Page(s) 1685

Abstract: HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea). However, the frequent neo-expression of HLA-G in many cancer types has been ... ...

Abstract	HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea). However, the frequent neo-expression of HLA-G in many cancer types has been previously and extensively described and is correlated with a bad prognosis. Despite being an MHC class I molecule, HLA-G is highly present in tumor context and shows unique characteristics of tissue restriction of a Tumor Associated Antigen (TAA), and potent immunosuppressive activity of an Immune CheckPoint (ICP). Consequently, HLA-G appears to be an excellent molecular target for immunotherapy. Although the relevance of HLA-G in cancer incidence and development has been proven in numerous tumors, its neo-expression pattern is still difficult to determine. Indeed, the estimation of HLA-G's actual expression in tumor tissue is limited, particularly concerning the presence and percentage of the new non-canonical isoforms, for which detection antibodies are scarce or inexistent. Here, we summarize the current knowledge about HLA-G neo-expression and implication in various tumor types, pointing out the need for the development of new tools to analyze in-depth the HLA-G neo-expression patterns, opening the way for the generation of new monoclonal antibodies and cell-based immunotherapies.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; Antineoplastic Agents, Immunological/therapeutic use ; HLA-G Antigens/immunology ; HLA-G Antigens/metabolism ; Humans ; Immunotherapy, Adoptive ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Tumor Escape ; Tumor Microenvironment
Chemical Substances	Antibodies, Monoclonal ; Antigens, Neoplasm ; Antineoplastic Agents, Immunological ; HLA-G Antigens
Language	English
Publishing date	2020-08-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01685
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Article ; Online: Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC.

Wu, Ching-Lien / Caumartin, Julien / Amodio, Giada / Anna, François / Loustau, Maria / Gregori, Silvia / Langlade-Demoyen, Pierre / LeMaoult, Joel

Frontiers in immunology

2021 Volume 11, Page(s) 608614

Abstract: Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance ... ...

Abstract	Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on iNKT cell-based anti-cancer are ongoing, however results are not as striking as in murine models. Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint molecule involved in fetal-maternal tolerance and in tumor immune escape. HLA-G exerts its immunomodulatory functions through the interaction with immune inhibitory receptors such as ILT2, differentially expressed on immune cell subsets. We hypothesized that HLA-G might inhibit iNKT function directly or by inducing tolerogenic APC leading to iNKT cell anergy, which could impact the results of current clinical trials. Using an ILT2-transduced murine iNKT cell line and human iNKT cells, we demonstrate that iNKT cells are sensitive to HLA-G, which inhibits their cytokine secretion. Furthermore, human HLA-G
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD/immunology ; Cells, Cultured ; Cytokines/immunology ; Dendritic Cells/immunology ; HLA-G Antigens/immunology ; Humans ; Immune Tolerance/immunology ; Leukocyte Immunoglobulin-like Receptor B1/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/immunology
Chemical Substances	Antigens, CD ; Cytokines ; HLA-G Antigens ; LILRB1 protein, human ; Leukocyte Immunoglobulin-like Receptor B1
Language	English
Publishing date	2021-01-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.608614
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Article ; Online: Full eradication of pre-clinical human papilloma virus-induced tumors by a lentiviral vaccine.

Douguet, Laëtitia / Fert, Ingrid / Lopez, Jodie / Vesin, Benjamin / Le Chevalier, Fabien / Moncoq, Fanny / Authié, Pierre / Nguyen, Trang-My / Noirat, Amandine / Névo, Fabien / Blanc, Catherine / Bourgine, Maryline / Hardy, David / Anna, François / Majlessi, Laleh / Charneau, Pierre

EMBO molecular medicine

2023 Volume 15, Issue 10, Page(s) e17723

Abstract: Human papillomavirus (HPV) infections are the cause of all cervical and numerous oropharyngeal and anogenital cancers. The currently available HPV vaccines, which induce neutralizing antibodies, have no therapeutic effect on established tumors. Here, we ... ...

Abstract	Human papillomavirus (HPV) infections are the cause of all cervical and numerous oropharyngeal and anogenital cancers. The currently available HPV vaccines, which induce neutralizing antibodies, have no therapeutic effect on established tumors. Here, we developed an immuno-oncotherapy against HPV-induced tumors based on a non-integrative lentiviral vector encoding detoxified forms of the Early E6 and E7 oncoproteins of HPV16 and 18 genotypes, namely, "Lenti-HPV-07". A single intramuscular injection of Lenti-HPV-07 into mice bearing established HPV-induced tumors resulted in complete tumor eradication in 100% of the animals and was also effective against lung metastases. This effect correlated with CD8
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.202317723
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Article ; Online: Mice humanized for MHC and hACE2 with high permissiveness to SARS-CoV-2 omicron replication.

Le Chevalier, Fabien / Authié, Pierre / Chardenoux, Sébastien / Bourgine, Maryline / Vesin, Benjamin / Cussigh, Delphine / Sassier, Yohann / Fert, Ingrid / Noirat, Amandine / Nemirov, Kirill / Anna, François / Bérard, Marion / Guinet, Françoise / Hardy, David / Charneau, Pierre / Lemonnier, François / Langa-Vives, Francina / Majlessi, Laleh

Microbes and infection

2023 Volume 25, Issue 7, Page(s) 105142

Abstract: Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are ... ...

Abstract	Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in "HHD-DR1" background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE2
MeSH term(s)	Animals ; Mice ; Humans ; Angiotensin-Converting Enzyme 2/genetics ; SARS-CoV-2/genetics ; COVID-19 Vaccines ; Permissiveness ; COVID-19 ; Major Histocompatibility Complex ; Mice, Transgenic
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; COVID-19 Vaccines
Language	English
Publishing date	2023-04-19
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2023.105142
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Zs.A 5014: Show issues

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Article ; Online: A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4

Lopez, Jodie / Anna, François / Authié, Pierre / Pawlik, Alexandre / Ku, Min-Wen / Blanc, Catherine / Souque, Philippe / Moncoq, Fanny / Noirat, Amandine / Hardy, David / Sougakoff, Wladimir / Brosch, Roland / Guinet, Françoise / Charneau, Pierre / Majlessi, Laleh

Cell reports

2022 Volume 40, Issue 4, Page(s) 111142

Abstract: Lentiviral vectors (LVs) are highly efficient at inducing ... ...

Abstract	Lentiviral vectors (LVs) are highly efficient at inducing CD8
MeSH term(s)	Animals ; Antigens, Bacterial ; Antigens, Differentiation, B-Lymphocyte ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Genetic Vectors ; Histocompatibility Antigens Class II ; Lentivirus ; Mice ; Mice, Inbred C57BL ; Mycobacteriaceae ; Mycobacterium tuberculosis
Chemical Substances	Antigens, Bacterial ; Antigens, Differentiation, B-Lymphocyte ; Histocompatibility Antigens Class II ; invariant chain
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111142
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Article ; Online: A Single Dose of NILV-Based Vaccine Provides Rapid and Durable Protection against Zika Virus.

Ku, Min Wen / Anna, François / Souque, Philippe / Petres, Stéphane / Prot, Matthieu / Simon-Loriere, Etienne / Charneau, Pierre / Bourgine, Maryline

Molecular therapy : the journal of the American Society of Gene Therapy

2020 Volume 28, Issue 8, Page(s) 1772–1782

Abstract: Zika virus, a member of the Flaviviridae family, is primarily transmitted by infected Aedes species mosquitoes. In 2016, Zika infection emerged as a global health emergency for its explosive spread and the remarkable neurological defects in the ... ...

Abstract	Zika virus, a member of the Flaviviridae family, is primarily transmitted by infected Aedes species mosquitoes. In 2016, Zika infection emerged as a global health emergency for its explosive spread and the remarkable neurological defects in the developing fetus. Development of a safe and effective Zika vaccine remains a high priority owing to the risk of re-emergence and limited understanding of Zika virus epidemiology. We engineered a non-integrating lentiviralvector(NILV)-based Zika vaccine encoding the consensus pre-membrane and envelope glycoprotein of circulating Zika virus strains. We further evaluated the immunogenicity and protective efficacy of this vaccine in both immunocompromised and immunocompetent mouse models. A single immunization in both mouse models elicited a robust neutralizing antibody titer and afforded full protection against Zika challenge as early as 7 days post-immunization. This NILV-based vaccine also induced a long-lasting immunity when immunized mice were challenged 6 months after immunization. Altogether, our NILV Zika vaccine provides a rapid yet durable protection through a single dose of immunization without extra adjuvant formulation. Our data suggest a promising Zika vaccine candidate for an emergency situation, and demonstrate the capacity of lentiviral vector as an efficient vaccine delivery platform.
MeSH term(s)	Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Cross Reactions/immunology ; Disease Models, Animal ; Genetic Vectors/genetics ; Host-Pathogen Interactions/immunology ; Immunization ; Immunogenicity, Vaccine ; Lentivirus/genetics ; Mice ; Vaccines, DNA/administration & dosage ; Vaccines, DNA/genetics ; Vaccines, DNA/immunology ; Viral Envelope Proteins/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/genetics ; Viral Vaccines/immunology ; Zika Virus/immunology ; Zika Virus Infection/prevention & control
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, DNA ; Viral Envelope Proteins ; Viral Vaccines
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2020.05.016
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Article: Full-Lung Prophylaxis against SARS-CoV-2 by One-Shot or Booster Intranasal Lentiviral Vaccination in Syrian Golden Hamsters.

Vesin, Benjamin / Authié, Pierre / Blanc, Catherine / Fert, Ingrid / Noirat, Amandine / Le Chevalier, Fabien / Wei, Yu / Ku, Min-Wen / Nemirov, Kirill / Anna, François / Hardy, David / Planchais, Cyril / Mouquet, Hugo / Guinet, Françoise / Charneau, Pierre / Majlessi, Laleh / Bourgine, Maryline

Vaccines

2022 Volume 11, Issue 1

Abstract: Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non- ... ...

Abstract	Following the breakthrough of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in recent months and the incomplete efficiency of the currently available vaccines, development of more effective vaccines is desirable. Non-integrative, non-cytopathic and non-inflammatory lentiviral vectors elicit sterilizing prophylaxis against SARS-CoV-2 in preclinical animal models and are particularly suitable for mucosal vaccination, which is acknowledged as the most effective in reducing viral transmission. Here, we demonstrate that a single intranasal administration of a vaccinal lentiviral vector encoding a stabilized form of the original SARS-CoV-2 Spike glycoprotein induces full-lung protection of respiratory tracts and strongly reduces pulmonary inflammation in the susceptible Syrian golden hamster model against the prototype SARS-CoV-2. In addition, we show that a lentiviral vector encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::S
Language	English
Publishing date	2022-12-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11010012
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Article ; Online: A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4

Anna, François / Lopez, Jodie / Moncoq, Fanny / Blanc, Catherine / Authié, Pierre / Noirat, Amandine / Fert, Ingrid / Souque, Philippe / Nevo, Fabien / Pawlik, Alexandre / Hardy, David / Goyard, Sophie / Hudrisier, Denis / Brosch, Roland / Guinet, Françoise / Neyrolles, Olivier / Charneau, Pierre / Majlessi, Laleh

Mucosal immunology

2022 Volume 15, Issue 6, Page(s) 1389–1404

Abstract: Most viral vectors, including the potently immunogenic lentiviral vectors (LVs), only poorly direct antigens to the MHC-II endosomal pathway and elicit ... ...

Abstract	Most viral vectors, including the potently immunogenic lentiviral vectors (LVs), only poorly direct antigens to the MHC-II endosomal pathway and elicit CD4
MeSH term(s)	Mice ; Animals ; CD8-Positive T-Lymphocytes ; CD4-Positive T-Lymphocytes ; Dendritic Cells ; Mice, Inbred C57BL ; Genetic Vectors/genetics
Language	English
Publishing date	2022-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-022-00566-z
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Zs.A 6796: Show issues

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Article ; Online: An intranasal lentiviral booster reinforces the waning mRNA vaccine-induced SARS-CoV-2 immunity that it targets to lung mucosa.

Vesin, Benjamin / Lopez, Jodie / Noirat, Amandine / Authié, Pierre / Fert, Ingrid / Le Chevalier, Fabien / Moncoq, Fanny / Nemirov, Kirill / Blanc, Catherine / Planchais, Cyril / Mouquet, Hugo / Guinet, Françoise / Hardy, David / Vives, Francina Langa / Gerke, Christiane / Anna, François / Bourgine, Maryline / Majlessi, Laleh / Charneau, Pierre

Molecular therapy : the journal of the American Society of Gene Therapy

2022 Volume 30, Issue 9, Page(s) 2984–2997

Abstract: As the coronavirus disease 2019 (COVID-19) pandemic continues and new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines starts waning ...

Abstract	As the coronavirus disease 2019 (COVID-19) pandemic continues and new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines starts waning 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 owing to its non-cytopathic, non-replicative, and scarcely inflammatory properties. 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::S
MeSH term(s)	Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Lung ; Mice ; Mucous Membrane ; SARS-CoV-2/genetics ; Vaccination ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2022.04.016
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