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Article: Recombinant poxviruses as mucosal vaccine vectors.

Gherardi, M Magdalena / Esteban, Mariano

2005 Volume 86, Issue Pt 11, Page(s) 2925–2936

Abstract: The majority of infections initiate their departure from a mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of mucosal immunity is a high priority in the development of vaccines against ... ...

Abstract	The majority of infections initiate their departure from a mucosal surface, such as Human immunodeficiency virus (HIV), a sexually transmitted virus. Therefore, the induction of mucosal immunity is a high priority in the development of vaccines against mucosal pathogens. The selection of an appropriate antigen delivery system is necessary to induce an efficient mucosal immune response. Poxvirus vectors have been the most intensively studied live recombinant vector, and numerous studies have demonstrated their ability to induce mucosal immune responses against foreign expressed antigens. Previous studies have demonstrated that recombinants based on the attenuated modified vaccinia virus Ankara (MVA) vector were effective in inducing protective responses against different respiratory viruses, such as influenza and respiratory syncytial virus, following immunization via mucosal routes. Recent studies performed in the murine and macaque models have shown that recombinant MVA (rMVA) does not only stimulate HIV-specific immunity in the genital and rectal tracts following mucosal delivery, but can also control simian/human immunodeficiency viraemia and disease progression. In addition, a prime-boost vaccination approach against tuberculosis emphasized the importance of the intranasal rMVA antigen delivery to induce protective immunity against Mycobacterium tuberculosis. The aim of this review is to summarize the studies employing recombinant poxviruses, specifically rMVA as a mucosal delivery vector. The results demonstrate that rMVAs can activate specific immune responses at mucosal surfaces, and encourage further studies to characterize and improve the MVA mucosal immunogenicity of poxvirus vectors.
MeSH term(s)	AIDS Vaccines/administration & dosage ; AIDS Vaccines/immunology ; Animals ; Genetic Vectors/administration & dosage ; Genetic Vectors/genetics ; Humans ; Immunity, Mucosal/genetics ; Immunity, Mucosal/immunology ; Mucous Membrane/immunology ; Mucous Membrane/virology ; Poxviridae/genetics ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology
Chemical Substances	AIDS Vaccines ; Vaccines, Synthetic
Keywords	covid19
Language	English
Publishing date	2005-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/vir.0.81181-0
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Article ; Online: Interplay between modified vaccinia virus Ankara and dendritic cells: phenotypic and functional maturation of bystander dendritic cells.

Pascutti, María F / Rodríguez, Ana M / Falivene, Juliana / Giavedoni, Luis / Drexler, Ingo / Gherardi, M Magdalena

Journal of virology

2011 Volume 85, Issue 11, Page(s) 5532–5545

Abstract: Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus strain, currently under evaluation as a vaccine vector in various clinical settings. It has been reported that human dendritic cells (DCs) mature after infection with MVA, but reports on the ... ...

Abstract	Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus strain, currently under evaluation as a vaccine vector in various clinical settings. It has been reported that human dendritic cells (DCs) mature after infection with MVA, but reports on the functionality of DCs have so far been controversial. In this work, we studied the phenotype and functionality of MVA-infected DCs. As previously reported, we found that human monocyte-derived DCs upregulated CD86 and HLA-DR in response to MVA infection. Moreover, infected DCs produced a broad array of chemokines and cytokines and were able to activate and induce gamma interferon (IFN-γ) production both in CD4(+) and in CD8(+) allogeneic T cells and in specific autologous peripheral blood lymphocytes (PBLs). Analysis of DC maturation following infection with a recombinant green fluorescent protein (GFP)-expressing MVA revealed that upregulation of CD86 expression was mainly observed in GFP(neg) (bystander) cells. While GFP(pos) (infected) DCs produced tumor necrosis factor alpha (TNF-α), they were unable to produce CXCL10 and were less efficient at inducing IFN-γ production in CEF-specific autologous PBLs. Maturation of bystander DCs could be achieved by incubation with supernatant from infected cultures or with apoptotic infected cells. Type I IFNs were partially responsible for the induction of CXCL10 on bystander DCs. Our findings demonstrate for the first time that, in MVA-infected DC cultures, the leading role with respect to functionality and maturation characteristics is achieved by the bystander DCs.
MeSH term(s)	B7-2 Antigen/analysis ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cytokines/metabolism ; Dendritic Cells/chemistry ; Dendritic Cells/immunology ; HLA-DR Antigens/analysis ; Humans ; Interferon-gamma/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vaccinia virus/immunology
Chemical Substances	B7-2 Antigen ; CD86 protein, human ; Cytokines ; HLA-DR Antigens ; Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2011-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02267-10
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Article: MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis.

Pérez-Jiménez, Eva / Kochan, Grazyna / Gherardi, M Magdalena / Esteban, Mariano

Microbes and infection

2006 Volume 8, Issue 3, Page(s) 810–822

Abstract: An optimal vaccine against leishmaniasis should elicit parasite specific CD4+ and cytotoxic CD8+ T cells. In this investigation, we described a prime/boost immunization approach based on DNA and on poxvirus vectors (Western Reserve, WR, and the highly ... ...

Abstract	An optimal vaccine against leishmaniasis should elicit parasite specific CD4+ and cytotoxic CD8+ T cells. In this investigation, we described a prime/boost immunization approach based on DNA and on poxvirus vectors (Western Reserve, WR, and the highly attenuated modified vaccinia virus Ankara, MVA), both expressing the LACK antigen of Leishmania infantum, that triggers different levels of specific CD8+ T cell responses and protection (reduction in lesion size and parasitemia) against L. major infection in mice. A prime/boost vaccination with DNA-LACK/MVA-LACK elicits higher CD8+ T cell responses than a similar protocol with the replication competent VV-LACK. Both CD4+ and CD8+ T cells were induced by DNA-LACK/MVA-LACK immunization. The levels of IFN-gamma and TNF-alpha secreting CD8+ T cells were higher in splenocytes from DNA-LACK/MVA-LACK than in DNA-LACK/VV-LACK immunized animals. Moreover, protection against L. major was significantly higher in DNA-LACK/MVA-LACK than in DNA-LACK/VV-LACK immunized animals when boosted with the same virus dose, and correlated with high levels of IFN-gamma and TNF-alpha secreting CD8+ T cells. In DNA-LACK/MVA-LACK vaccinated animals, the extent of lesion size reduction ranged from 65 to 92% and this protection was maintained for at least 17 weeks after challenge with the parasite. These findings demonstrate that in heterologous prime/boost immunization approaches, the protocol DNA-LACK/MVA-LACK is superior to DNA-LACK/VV-LACK in triggering specific CD8+ T cell immune responses and in conferring protection against cutaneous leishmaniasis. Thus, MVA-LACK is a safe and efficient vector for vaccination against leishmaniasis.
MeSH term(s)	Animals ; Antigens, Protozoan/genetics ; Antigens, Protozoan/immunology ; DNA, Protozoan ; Drug Administration Schedule ; Female ; Immunization, Secondary ; Interferon-gamma/metabolism ; Leishmania major ; Leishmaniasis, Cutaneous/immunology ; Leishmaniasis, Cutaneous/pathology ; Leishmaniasis, Cutaneous/prevention & control ; Mice ; Mice, Inbred BALB C ; Protozoan Proteins/genetics ; Protozoan Proteins/immunology ; Protozoan Vaccines/adverse effects ; Protozoan Vaccines/genetics ; Protozoan Vaccines/immunology ; T-Lymphocytes/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vaccines, Synthetic/adverse effects ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Vaccinia virus
Chemical Substances	Antigens, Protozoan ; DNA, Protozoan ; Protozoan Proteins ; Protozoan Vaccines ; Tumor Necrosis Factor-alpha ; Vaccines, Synthetic ; LACK antigen, Leishmania (163832-69-7) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2006-03
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.2005.10.004
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Article: IL-12 and IL-18 act in synergy to clear vaccinia virus infection: involvement of innate and adaptive components of the immune system.

Gherardi, M Magdalena / Ramírez, Juan C / Esteban, Mariano

The Journal of general virology

2001 Volume 84, Issue Pt 8, Page(s) 1961–1972

Abstract: Development of a protective host response against intracellular pathogens requires innate and cell-mediated immune responses, with cytokines playing an important role in host defences. Different studies in mice have shown that IL-12 can promote ... ...

Abstract	Development of a protective host response against intracellular pathogens requires innate and cell-mediated immune responses, with cytokines playing an important role in host defences. Different studies in mice have shown that IL-12 can promote protective immunity to a variety of viruses but, during virus infection, little is known about the in vivo function of IL-18 alone or in combination with IL-12. Using recombinant vaccinia viruses (rVVs) expressing IL-12 and IL-18, the antiviral role of both cytokines in mice has been analysed. The specific anti-VV immune response elicited and the persistence of the virus in target tissues were compared in BALB/c mice inoculated with rVVs expressing IL-12 and IL-18 either singly or in combination. Delivery of IL-12 and IL-18 by rVVs in mice induced a significant enhancement in virus clearance from ovaries and spleen, greater than that expected from the sum of action of both cytokines. Virus clearance involved NK and T cells, as demonstrated in mice depleted of NK cells and in immunodeficient SCID animals. Th1 parameters (CD8(+) T cell response and IgG2a : IgG1 ratios) were increased in mice inoculated with rVVs expressing both IL-12 and IL-18 as compared to those animals receiving a single cytokine. These findings indicate that when IL-12 and IL-18 are delivered by rVVs, different mechanisms involving both the innate and specific arms of the immune system act as mediators in the synergistic action of IL-12 and IL-18, leading to VV clearance. These results are of interest for the design of prophylactic as well as therapeutic VV-based strategies.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Antiviral Agents/pharmacology ; Drug Synergism ; Female ; Immunity, Innate ; Interleukin-12/genetics ; Interleukin-12/immunology ; Interleukin-12/pharmacology ; Interleukin-18/genetics ; Interleukin-18/immunology ; Interleukin-18/pharmacology ; Killer Cells, Natural/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Ovary/immunology ; Ovary/virology ; Recombination, Genetic ; Spleen/immunology ; Spleen/virology ; T-Lymphocytes/immunology ; Vaccinia/immunology ; Vaccinia/virology ; Vaccinia virus/drug effects ; Vaccinia virus/genetics ; Vaccinia virus/growth & development
Chemical Substances	Antibodies, Viral ; Antiviral Agents ; Interleukin-18 ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2001-10-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/vir.0.19120-0
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Article: Induction of HIV immunity in the genital tract after intranasal delivery of a MVA vector: enhanced immunogenicity after DNA prime-modified vaccinia virus Ankara boost immunization schedule.

Gherardi, M Magdalena / Pérez-Jiménez, Eva / Nájera, José Luis / Esteban, Mariano

Journal of immunology (Baltimore, Md. : 1950)

2004 Volume 172, Issue 10, Page(s) 6209–6220

Abstract: Vaccines intended to prevent mucosal transmission of HIV should be able to induce multiple immune effectors in the host including Abs and cell-mediated immune responses at mucosal sites. The aim of this study was to characterize and to enhance the ... ...

Abstract	Vaccines intended to prevent mucosal transmission of HIV should be able to induce multiple immune effectors in the host including Abs and cell-mediated immune responses at mucosal sites. The aim of this study was to characterize and to enhance the immunogenicity of a recombinant modified vaccinia virus Ankara (MVA) expressing HIV-1 Env IIIB Ag (MVAenv) inoculated in BALB/c mice by mucosal routes. Intravaginal inoculation of MVAenv was not immunogenic, whereas intranasally it induced a significant immune response to the HIV Ag. Intranasal codelivery of MVAenv plus cholera toxin (CT) significantly enhanced the cellular and humoral immune response against Env in the spleen and genitorectal draining lymph nodes, respectively. Heterologous DNAenv prime-MVAenv boost by intranasal immunization, together with CT, produced a cellular immune response in the spleen 10-fold superior to that in the absence of CT. A key finding of these studies was that both MVAenv/MVAenv and DNAenv/MVAenv schemes, plus CT, induced a specific mucosal CD8(+) T cell response in genital tissue and draining lymph nodes. In addition, both immunizations also generated systemic Abs, and more importantly, mucosal IgA and IgG Abs in vaginal washings. Specific secretion of beta-chemokines was also generated by both immunizations, with a stronger response in mice immunized by the DNA-CT/MVA-CT regimen. Our findings are of relevance in the area of vaccine development and support the optimization of protocols of immunization based on MVA as vaccine vectors to induce mucosal immune responses against HIV.
MeSH term(s)	AIDS Vaccines/administration & dosage ; AIDS Vaccines/genetics ; AIDS Vaccines/immunology ; Adjuvants, Immunologic/administration & dosage ; Adjuvants, Immunologic/genetics ; Administration, Intranasal ; Administration, Intravaginal ; Animals ; Cholera Toxin/administration & dosage ; Cholera Toxin/immunology ; Female ; Gene Products, env/biosynthesis ; Gene Products, env/immunology ; Genetic Vectors ; HIV Antibodies/biosynthesis ; HIV-1/genetics ; HIV-1/immunology ; Immunity, Cellular ; Immunity, Mucosal/genetics ; Immunization Schedule ; Immunization, Secondary/methods ; Interferon-gamma/metabolism ; Lymph Nodes/immunology ; Lymph Nodes/metabolism ; Lymph Nodes/virology ; Mice ; Mice, Inbred BALB C ; Rectum/immunology ; Rectum/pathology ; Rectum/virology ; Urogenital System/immunology ; Urogenital System/virology ; Vaccines, DNA/administration & dosage ; Vaccines, DNA/genetics ; Vaccines, DNA/immunology ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Vaccinia virus/genetics ; Vaccinia virus/immunology ; Vaccinia virus/physiology ; Virus Replication/immunology
Chemical Substances	AIDS Vaccines ; Adjuvants, Immunologic ; Gene Products, env ; HIV Antibodies ; Vaccines, DNA ; Vaccines, Synthetic ; Interferon-gamma (82115-62-6) ; Cholera Toxin (9012-63-9)
Language	English
Publishing date	2004-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.172.10.6209
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Article ; Online: T-cell immune responses against Env from CRF12_BF and subtype B HIV-1 show high clade-specificity that can be overridden by multiclade immunizations.

Mónaco, Daniela C / Rodríguez, Ana M / Pascutti, María F / Carobene, Mauricio / Falivene, Juliana / Gómez, Alejandro / Maeto, Cynthia / Turk, Gabriela / Nájera, José L / Esteban, Mariano / Gherardi, M Magdalena

PloS one

2011 Volume 6, Issue 2, Page(s) e17185

Abstract: Background: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections ... ...

Abstract	Background: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors. Methodology/principal findings: As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B. Conclusions/significance: This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate.
MeSH term(s)	AIDS Vaccines/therapeutic use ; Amino Acid Sequence ; Animals ; BALB 3T3 Cells ; Cells, Cultured ; Female ; HIV Antigens/genetics ; HIV Antigens/immunology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV-1/classification ; HIV-1/genetics ; HIV-1/immunology ; HeLa Cells ; Humans ; Immunity, Cellular/immunology ; Immunization/methods ; Mice ; Mice, Inbred BALB C ; Models, Biological ; Molecular Sequence Data ; T-Cell Antigen Receptor Specificity/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/physiology ; env Gene Products, Human Immunodeficiency Virus/chemistry ; env Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; HIV Antigens ; env Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2011-02-18
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0017185
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Article ; Online: Deletion of A44L, A46R and C12L Vaccinia Virus Genes from the MVA Genome Improved the Vector Immunogenicity by Modifying the Innate Immune Response Generating Enhanced and Optimized Specific T-Cell Responses.

Holgado, María Pía / Falivene, Juliana / Maeto, Cynthia / Amigo, Micaela / Pascutti, María Fernanda / Vecchione, María Belén / Bruttomesso, Andrea / Calamante, Gabriela / Del Médico-Zajac, María Paula / Gherardi, María Magdalena

Viruses

2016 Volume 8, Issue 5

Abstract: MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the ... ...

Abstract	MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R); or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R). The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b⁺/IFN-γ⁺) and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential.
MeSH term(s)	Animals ; Antigens, Viral/immunology ; Cytokines/secretion ; Epitopes/immunology ; Immunity, Innate ; Lymph Nodes/immunology ; Mice, Inbred C57BL ; Sequence Deletion ; Spleen/immunology ; T-Lymphocytes/immunology ; Vaccinia virus/genetics ; Vaccinia virus/immunology ; Viral Proteins/genetics
Chemical Substances	A46R protein, vaccinia virus ; Antigens, Viral ; C12L protein, vaccinia virus ; Cytokines ; Epitopes ; Viral Proteins
Language	English
Publishing date	2016-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v8050139
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Article ; Online: T-cell immune responses against Env from CRF12_BF and subtype B HIV-1 show high clade-specificity that can be overridden by multiclade immunizations.

Daniela C Mónaco / Ana M Rodríguez / María F Pascutti / Mauricio Carobene / Juliana Falivene / Alejandro Gómez / Cynthia Maeto / Gabriela Turk / José L Nájera / Mariano Esteban / M Magdalena Gherardi

PLoS ONE, Vol 6, Iss 2, p e

2011 Volume 17185

Abstract: BACKGROUND: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections ... ...

Abstract	BACKGROUND: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors. METHODOLOGY/PRINCIPAL FINDINGS: As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B. CONCLUSIONS/SIGNIFICANCE: This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

Rodríguez, Dolores / González-Aseguinolaza, Gloria / Rodríguez, Juan R / Vijayan, Aneesh / Gherardi, Magdalena / Rueda, Paloma / Casal, J Ignacio / Esteban, Mariano

PloS one

2012 Volume 7, Issue 4, Page(s) e34445

Abstract: With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii ...

Abstract	With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Chick Embryo ; Chlorocebus aethiops ; Female ; Immunization, Secondary ; Liver/immunology ; Liver/parasitology ; Malaria/prevention & control ; Malaria Vaccines/genetics ; Malaria Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Parvovirus, Porcine/genetics ; Parvovirus, Porcine/immunology ; Parvovirus, Porcine/ultrastructure ; Plasmodium yoelii/immunology ; Protozoan Proteins/genetics ; Protozoan Proteins/immunology ; Vaccines, Virus-Like Particle/genetics ; Vaccines, Virus-Like Particle/immunology ; Vaccines, Virus-Like Particle/ultrastructure ; Vaccinia virus/genetics ; Vaccinia virus/immunology ; Virus Replication
Chemical Substances	Malaria Vaccines ; Protozoan Proteins ; Vaccines, Virus-Like Particle ; circumsporozoite protein, Protozoan
Language	English
Publishing date	2012-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0034445
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Article ; Online: Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

Turk, Gabriela / Ghiglione, Yanina / Hormanstorfer, Macarena / Laufer, Natalia / Coloccini, Romina / Salido, Jimena / Trifone, César / Ruiz, María Julia / Falivene, Juliana / Holgado, María Pía / Caruso, María Paula / Figueroa, María Inés / Salomón, Horacio / Giavedoni, Luis D / Pando, María de Los Ángeles / Gherardi, María Magdalena / Rabinovich, Roberto Daniel / Pury, Pedro A / Sued, Omar

Viruses

2018 Volume 10, Issue 1

Abstract: Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A ... ...

Abstract	Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation (
MeSH term(s)	Acute Disease ; Adult ; Biomarkers/blood ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; Chemokine CXCL10/blood ; Cytokines/immunology ; Disease Progression ; Female ; HIV Infections/blood ; HIV Infections/diagnosis ; HIV-1 ; Humans ; Male ; Receptors, CCR5/blood ; Viral Load
Chemical Substances	Biomarkers ; CCR5 protein, human ; CXCL10 protein, human ; Chemokine CXCL10 ; Cytokines ; Receptors, CCR5
Language	English
Publishing date	2018-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v10010034
Database	MEDical Literature Analysis and Retrieval System OnLINE

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