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Article ; Online: The importance of semen leukocytes in HIV-1 transmission and the development of prevention strategies.

Cavarelli, Mariangela / Le Grand, Roger

2020 Volume 16, Issue 9, Page(s) 2018–2032

Abstract: HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and ...

Abstract	HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and that are harnessed to efficiently interact with mucosal barriers exposed during sexual intercourse. Several cofactors contribute to semen infectivity and may enhance the risk of HIV-1 transmission to a partner by increasing local HIV-1 replication in the male genital tract, thereby increasing the number of HIV-1-infected cells and the local HIV-1 shedding in semen. The introduction of combination antiretroviral therapy has improved the life expectancy of HIV-1 infected individuals; however, there is evidence that systemic viral suppression does not always reflect full viral suppression in the seminal compartment. This review focus on the role semen leukocytes play in HIV-1 transmission and discusses implications of the increased resistance of cell-mediated transmission to immune-based prevention strategies.
MeSH term(s)	Anti-Retroviral Agents/therapeutic use ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; HIV-1 ; Humans ; Leukocytes ; Male ; Semen ; Virus Shedding
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2020-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2020.1765622
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Article ; Online: Isolation and phenotypic characterization of human and nonhuman primate intestinal lamina propria mononuclear cells.

Benmeziane, Keltouma / Delache, Benoit / Langlois, Sébastien / Scarlatti, Gabriella / Le Grand, Roger / Cavarelli, Mariangela

STAR protocols

2022 Volume 3, Issue 4, Page(s) 101815

Abstract: ... details on the use and execution of this protocol, please refer to Cavarelli et al. (2022). ...

Abstract	Isolation of viable immune cells from tissues is critically important to characterize cellular and molecular processes during homeostasis and disease. Here, we provide an optimized protocol to achieve high yields of viable intestinal lamina propria mononuclear cells (LPMCs). We describe steps for intestinal tissue collection from humans and nonhuman primates, followed by mechanical disruption and enzymatic digestion. Furthermore, we detail characterization of the mononuclear phagocyte (MP) subtypes by flow cytometry analysis. The protocol is repeatable and scalable for downstream applications. For complete details on the use and execution of this protocol, please refer to Cavarelli et al. (2022).
MeSH term(s)	Animals ; Humans ; Intestinal Mucosa ; Flow Cytometry/methods ; Leukocytes ; Primates
Language	English
Publishing date	2022-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101815
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Article ; Online: Isolation and phenotypic characterization of human and nonhuman primate intestinal lamina propria mononuclear cells

Keltouma Benmeziane / Benoit Delache / Sébastien Langlois / Gabriella Scarlatti / Roger Le Grand / Mariangela Cavarelli

STAR Protocols, Vol 3, Iss 4, Pp 101815- (2022)

2022

Abstract: ... on the use and execution of this protocol, please refer to Cavarelli et al. (2022). : Publisher’s note ...

Abstract	Summary: Isolation of viable immune cells from tissues is critically important to characterize cellular and molecular processes during homeostasis and disease. Here, we provide an optimized protocol to achieve high yields of viable intestinal lamina propria mononuclear cells (LPMCs). We describe steps for intestinal tissue collection from humans and nonhuman primates, followed by mechanical disruption and enzymatic digestion. Furthermore, we detail characterization of the mononuclear phagocyte (MP) subtypes by flow cytometry analysis. The protocol is repeatable and scalable for downstream applications.For complete details on the use and execution of this protocol, please refer to Cavarelli et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Keywords	Cell isolation ; Flow Cytometry/Mass Cytometry ; Immunology ; Science (General) ; Q1-390
Subject code	004
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children.

Dispinseri, Stefania / Cavarelli, Mariangela / Tolazzi, Monica / Plebani, Anna Maria / Jansson, Marianne / Scarlatti, Gabriella

Vaccines

2021 Volume 9, Issue 3

Abstract: The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these ...

Abstract	The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.
Language	English
Publishing date	2021-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9030260
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Article ; Online: Identification of CX3CR1

Cavarelli, Mariangela / Foglieni, Chiara / Hantour, Naima / Schorn, Tilo / Ferrazzano, Antonello / Dispinseri, Stefania / Desjardins, Delphine / Elmore, Ugo / Dereuddre-Bosquet, Nathalie / Scarlatti, Gabriella / Le Grand, Roger

iScience

2022 Volume 25, Issue 6, Page(s) 104346

Abstract: The difficulty to unambiguously identify the various subsets of mononuclear phagocytes (MNPs) of the ... ...

Abstract	The difficulty to unambiguously identify the various subsets of mononuclear phagocytes (MNPs) of the intestinal
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104346
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Article ; Online: Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure.

Suphaphiphat, Karunasinee / Desjardins, Delphine / Lorin, Valérie / Dimant, Nastasia / Bouchemal, Kawthar / Bossevot, Laetitia / Galpin-Lebreau, Maxence / Dereuddre-Bosquet, Nathalie / Mouquet, Hugo / Le Grand, Roger / Cavarelli, Mariangela

Nature communications

2023 Volume 14, Issue 1, Page(s) 6224

Abstract: Passive immunization using broadly neutralizing antibodies (bNAbs) is investigated in clinical settings to inhibit HIV-1 acquisition due to the lack of a preventive vaccine. However, bNAbs efficacy against highly infectious cell-associated virus ... ...

Abstract	Passive immunization using broadly neutralizing antibodies (bNAbs) is investigated in clinical settings to inhibit HIV-1 acquisition due to the lack of a preventive vaccine. However, bNAbs efficacy against highly infectious cell-associated virus transmission has been overlooked. HIV-1 transmission mediated by infected cells present in body fluids likely dominates infection and aids the virus in evading antibody-based immunity. Here, we show that the anti-N-glycans/V3 loop HIV-1 bNAb 10-1074 formulated for topical vaginal application in a microbicide gel provides significant protection against repeated cell-associated SHIV
MeSH term(s)	Animals ; Female ; Humans ; Broadly Neutralizing Antibodies ; Macaca ; Simian Acquired Immunodeficiency Syndrome ; Simian Immunodeficiency Virus ; Antibodies, Neutralizing ; HIV Antibodies ; HIV-1 ; HIV Infections
Chemical Substances	Broadly Neutralizing Antibodies ; Antibodies, Neutralizing ; HIV Antibodies
Language	English
Publishing date	2023-10-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41966-4
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Article ; Online: Intestinal immunological events of acute and resolved SARS-CoV-2 infection in non-human primates.

Hua, Stéphane / Latha, Krishna / Marlin, Romain / Benmeziane, Keltouma / Bossevot, Laetitia / Langlois, Sébastien / Relouzat, Francis / Dereuddre-Bosquet, Nathalie / Le Grand, Roger / Cavarelli, Mariangela

Mucosal immunology

2023 Volume 17, Issue 1, Page(s) 25–40

Abstract: SARS-CoV-2 infection has been associated with intestinal mucosal barrier damage, leading to microbial and endotoxin translocation, heightened inflammatory responses, and aggravated disease outcomes. This study aimed to investigate the immunological ... ...

Abstract	SARS-CoV-2 infection has been associated with intestinal mucosal barrier damage, leading to microbial and endotoxin translocation, heightened inflammatory responses, and aggravated disease outcomes. This study aimed to investigate the immunological mechanisms associated with impaired intestinal barrier function. We conducted a comprehensive analysis of gut damage and inflammation markers and phenotypic characterization of myeloid and lymphoid populations in the ileum and colon of SARS-CoV-2-exposed macaques during both the acute and resolved infection phases. Our findings revealed a significant accumulation of terminally differentiated and activated CD4+ and CD8+ T cells, along with memory B cells, within the gastrointestinal tract up to 43 days after exposure to SARS-CoV-2. This robust infection-induced immune response was accompanied by a notable depletion of plasmacytoid dendritic cells, myeloid dendritic cells, and macrophages, particularly affecting the colon during the resolved infection phase. Additionally, we identified a population of CX3CR1
MeSH term(s)	Animals ; COVID-19/pathology ; SARS-CoV-2 ; Intestinal Mucosa ; Inflammation ; Primates
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1016/j.mucimm.2023.10.001
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Article ; Online: Human seminal plasma stimulates the migration of CD11c+ mononuclear phagocytes to the apical side of the colonic epithelium without altering the junctional complexes in an

Baratella, Marco / Iannone, Valeria / Cavarelli, Mariangela / Foglieni, Chiara / Viganò, Paola / Moog, Christiane / Elmore, Ugo / Nozza, Silvia / Alfano, Massimo / Salonia, Andrea / Dispinseri, Stefania / Scarlatti, Gabriella

Frontiers in immunology

2023 Volume 14, Page(s) 1133886

Abstract: Introduction: Human immunodeficiency virus type 1 (HIV) transmission mostly occurs through the genital and intestinal mucosae. Although HIV-1 transmission has been extensively investigated, gaps remain in understanding the initial steps of HIV entry ... ...

Abstract	Introduction: Human immunodeficiency virus type 1 (HIV) transmission mostly occurs through the genital and intestinal mucosae. Although HIV-1 transmission has been extensively investigated, gaps remain in understanding the initial steps of HIV entry through the colonic mucosa. We previously showed that HIV can selectively trigger mononuclear phagocytes (MNP) to migrate within colonic epithelial cells to sample virions. Mucosal exposure to human seminal plasma (HSP), rich in pro- and anti-inflammatory cytokines, chemokines and growth factors, may as well induce alterations of the colonic mucosa and recruit immune cells, hence, affecting pathogen sampling and transmission. Methods: Here, we studied the role of HSP on the paracellular intestinal permeability by analyzing the distribution of two proteins known to play a key role in controlling the intestinal barrier integrity, namely the tight junctions-associated junctional adhesion molecule (JAM-A) and the adherents junction associated protein E-cadherin (E-CAD), by immunofluorescence and confocal microscopy. Also, we evaluated if HSP promotes the recruitment of MNP cells, specifically, the CD11c and CD64 positive MNPs, to the apical side of the human colonic mucosa. At this scope, HSP of HIV-infected and uninfected individuals with known fertility status was tested for cytokines, chemokines and growth factors concentration and used in an Results: HSP showed statistically significant differences in cytokines and chemokines concentrations between the three groups of donors, i.e. HIV infected, or uninfected fertile or randomly identified. Nevertheless, we showed that in the Discussion: In conclusion, even if HSP did not perturb the integrity of the human colonic mucosa, it affected the migration of a specific subset of MNPs that express CD11c towards the apical side of the colonic mucosa, which in turn may be involved in pathogen sampling.
MeSH term(s)	Humans ; Cadherins/immunology ; Cytokines/immunology ; Epithelium/immunology ; HIV Infections/immunology ; HIV Infections/transmission ; HIV Infections/virology ; Junctional Adhesion Molecules ; Phagocytes/immunology ; Semen/immunology ; Monocytes/immunology ; CD11c Antigen/immunology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/virology ; Colon/immunology ; Colon/virology ; HIV-1/immunology ; Cell Movement/immunology ; Virus Internalization ; Host-Pathogen Interactions/immunology
Chemical Substances	Cadherins ; Cytokines ; Junctional Adhesion Molecules ; CD11c Antigen ; F11R protein, human ; FCGR1A protein, human
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Clinical Study ; 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.2023.1133886
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Article ; Online: Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

Stefania Dispinseri / Mariangela Cavarelli / Monica Tolazzi / Anna Maria Plebani / Marianne Jansson / Gabriella Scarlatti

Vaccines, Vol 9, Iss 260, p

2021 Volume 260

Abstract	The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.
Keywords	HIV-1 ; neutralization ; ADCC ; children ; humoral immunity ; disease progression ; Medicine ; R
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques.

Galhaut, Mathilde / Lundberg, Urban / Marlin, Romain / Schlegl, Robert / Seidel, Stefan / Bartuschka, Ursula / Heindl-Wruss, Jürgen / Relouzat, Francis / Langlois, Sébastien / Dereuddre-Bosquet, Nathalie / Morin, Julie / Galpin-Lebreau, Maxence / Gallouët, Anne-Sophie / Gros, Wesley / Naninck, Thibaut / Pascal, Quentin / Chapon, Catherine / Mouchain, Karine / Fichet, Guillaume /

Lemaitre, Julien / Cavarelli, Mariangela / Contreras, Vanessa / Legrand, Nicolas / Meinke, Andreas / Le Grand, Roger

Communications medicine

2024 Volume 4, Issue 1, Page(s) 62

Abstract: Background: The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. ... ...

Abstract	Background: The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens that may improve response breadth and can be easily adapted every year to maintain preparedness for future seasonally emerging variants. Methods: The vaccine dose was determined using ELISA and pseudoviral particle-based neutralization assay in the mice. The immunogenicity was assessed in the non-human primates with multiplex ELISA, neutralization assays, ELISpot and intracellular staining. The efficacy was demonstrated by viral quantification in fluids using RT-qPCR and respiratory tissue lesions evaluation. Results: Here we report the immunogenicity and efficacy of VLA2001 in animal models. VLA2001 formulated with alum and the TLR9 agonist CpG 1018™ adjuvant generate a Th1-biased immune response and serum neutralizing antibodies in female BALB/c mice. In male cynomolgus macaques, two injections of VLA2001 are sufficient to induce specific and polyfunctional CD4 Conclusions: We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00488-w
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