EVHA T01 is an international, phase I/II, multicentre, multi-stage, double-blind study that will evaluate at least three experimental arms compared to placebo control in HIV-1 infected participants to see if one or more has a clinically relevant impact on the control of viral replication.

开始日期2019-02-20

申办/合作机构

ANRS, Emerging Infectious Diseases

[+11]

100 项与 MVATG-17401 相关的临床结果

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100 项与 MVATG-17401 相关的转化医学

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100 项与 MVATG-17401 相关的专利（医药）

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项与 MVATG-17401 相关的文献（医药）

2022-06-15·The Journal of Immunology

T Cell Immunogenicity, Gene Expression Profile, and Safety of Four Heterologous Prime-Boost Combinations of HIV Vaccine Candidates in Healthy Volunteers: Results of the Randomized Multi-Arm Phase I/II ANRS VRI01 Trial

Article

作者: Bonnabau, H. ; Paul, S. ; Thiebaut, Rodolphe ; Launay, Odile ; Preau, M. ; Diallo, A. ; Krief, C. ; Levy, Yves ; Wiedemann, A. ; Delahaye, S. ; Diallo, Alpha ; Couderc, M. ; Hardel, L. ; Tisserand, Pascaline ; Bouakane, A. ; Delobel, P. ; Levy, Y. ; Miloudi, S. ; Savarieau, H. ; Bourlet, T. ; Launay, O. ; Tisserand, P. ; Desaint, C. ; Richert, L. ; Walker, S. ; Hardel, Lucile ; Durand, Melany ; Centlivre, M. ; Lefebvre, Cecile ; Verlinde-Carvalho, M. ; Bauduin, Claire ; Gilbert, C. ; Amri, I. ; Hanot, L. ; Hocini, Hakim ; Thiebaut, R. ; Lucht, F. ; Foucat, E. ; Nedjaai, N. ; Bouvier, M. ; Hejblum, B. ; Rouby, F. ; Foucat, Emile ; Dumont, C. ; Melica, G. ; Poizot-Martin, Isabelle ; Fresard, A. ; Lacabaratz, C. ; Carcelain, G. ; Reijonen, K. ; Krivine, A. ; Clavier, E. ; Allais, F. ; Honore, S. ; Lelievre, J.-D. ; Wiedemann, Aurelie ; Grondin, C. ; Bauduin, C. ; Bodilis, H. ; Chesnel, C. ; Reboud, P. ; Wittkop, L. ; Durand, M. ; Tamalet, C. ; Giroud, A. ; Guillaumat, Lydia ; Hocini, H. ; Blengio, F. ; Fouilloux, P. ; Sommet, A. ; Guerin, C. ; Viard, J.-P. ; Davier, M. ; Rieux, Veronique ; Hanslik, T. ; Lhomme, E. ; Fries, I. ; Zaegel-Faucher, O. ; Dominguez, S. ; Rouch, Elodie ; Rouch, E. ; Lopez, J.-L. ; Colin de Verdiere, N. ; Ronat, V. ; Lefebvre, C. ; Deluca, B. ; Micallef, J. ; Niedziolka, P. Duchet ; Richert, Laura ; Arnold, V. ; Lucht, Frederic ; Loulergue, P. ; Lelievre, Jean-Daniel ; Poizot-Martin, I. ; Rieux, V. ; Perrier, A. ; Lacabaratz, Christine ; Barin, F. ; Ollivier-Yaniv, C. ; Surenaud, M. ; Fagard, C. ; Guillaumat, L. ; Terrier, F. ; Lemoine, F. ; Surenaud, Mathieu ; Hejblum, Boris

AbstractHeterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T cell responses. In this phase I/II multi-arm trial, three vaccine candidates were used as prime or boost: modified vaccinia Ankara (MVA) HIV-B (coding for Gag, Pol, Nef); HIV LIPO-5 (five lipopeptides from Gag, Pol, Nef); DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, Env gp160 clade B). Healthy human volunteers (n = 92) were randomized to four groups: 1) MVA at weeks 0/8 + LIPO-5 at weeks 20/28 (M/L); 2) LIPO-5 at weeks 0/8 + MVA at weeks 20/28 (L/M); 3) DNA at weeks 0/4/12 + LIPO-5 at weeks 20/28 (G/L); 4) DNA at weeks 0/4/12 + MVA at weeks 20/28 (G/M). The frequency of IFN-γ–ELISPOT responders at week 30 was 33, 43, 0, and 74%, respectively. Only MVA-receiving groups were further analyzed (n = 62). Frequency of HIV-specific cytokine-positive (IFN-γ, IL-2, or TNF-α) CD4+ T cells increased significantly from week 0 to week 30 (median change of 0.06, 0.11, and 0.10% for M/L, L/M, and G/M, respectively), mainly after MVA vaccinations, and was sustained until week 52. HIV-specific CD8+ T cell responses increased significantly at week 30 in M/L and G/M (median change of 0.02 and 0.05%). Significant whole-blood gene expression changes were observed 2 wk after the first MVA injection, regardless of its use as prime or boost. An MVA gene signature was identified, including 86 genes mainly related to cell cycle pathways. Three prime-boost strategies led to CD4+ and CD8+ T cell responses and to a whole-blood gene expression signature primarily due to their MVA HIV-B component.

PLoS ONE3区 · 综合性期刊

A Candidate HIV/AIDS Vaccine (MVA-B) Lacking Vaccinia Virus Gene C6L Enhances Memory HIV-1-Specific T-Cell Responses

3区 · 综合性期刊

ArticleOA

作者: Carmen E. Gómez ; Mariano Esteban ; Carlos Oscar S. Sorzano ; José Luis Nájera ; Thierry Roger ; Nolawit Tewabe ; Juan García-Arriaza ; Thierry Calandra

The vaccinia virus (VACV) C6 protein has sequence similarities with the poxvirus family Pox_A46, involved in regulation of host immune responses, but its role is unknown. Here, we have characterized the C6 protein and its effects in virus replication, innate immune sensing and immunogenicity in vivo. C6 is a 18.2 kDa protein, which is expressed early during virus infection and localizes to the cytoplasm of infected cells. Deletion of the C6L gene from the poxvirus vector MVA-B expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (MVA-B ΔC6L) had no effect on virus growth kinetics; therefore C6 protein is not essential for virus replication. The innate immune signals elicited by MVA-B ΔC6L in human macrophages and monocyte-derived dendritic cells (moDCs) are characterized by the up-regulation of the expression of IFN-β and IFN-α/β-inducible genes. In a DNA prime/MVA boost immunization protocol in mice, flow cytometry analysis revealed that MVA-B ΔC6L enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4+ and CD8+ T-cell memory immune responses, with most of the HIV-1 responses mediated by the CD8+ T-cell compartment with an effector phenotype. Significantly, while MVA-B induced preferentially Env- and Gag-specific CD8+ T-cell responses, MVA-B ΔC6L induced more Gag-Pol-Nef-specific CD8+ T-cell responses. Furthermore, MVA-B ΔC6L enhanced the levels of antibodies against Env in comparison with MVA-B. These findings revealed that C6 can be considered as an immunomodulator and that deleting C6L gene in MVA-B confers an immunological benefit by enhancing IFN-β-dependent responses and increasing the magnitude and quality of the T-cell memory immune responses to HIV-1 antigens. Our observations are relevant for the improvement of MVA vectors as HIV-1 vaccines.

PLoS ONE3区 · 综合性期刊

Immunogenic Profiling in Mice of a HIV/AIDS Vaccine Candidate (MVA-B) Expressing Four HIV-1 Antigens and Potentiation by Specific Gene Deletions

3区 · 综合性期刊

ArticleOA

作者: Carmen E. Gómez ; José Luis Nájera ; Mariano Esteban ; Carlos Oscar S. Sorzano ; Juan García-Arriaza

BACKGROUNDThe immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs) with immunoregulatory function.METHODOLOGY/PRINCIPAL FINDINGSIn an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R), known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R). A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1-specific CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+) T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env.CONCLUSIONS/SIGNIFICANCEThese findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R induced in mice robust, polyfunctional and durable T-cell responses to HIV-1 antigens, but the double deletion mutant showed enhanced magnitude and quality of HIV-1 adaptive and memory responses. Our observations are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors as HIV-1 vaccines.

100 项与 MVATG-17401 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床2期	-	El Paso ANRS Investments LLC	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ANRS/INSERM VRI01 (IAS2017)	N/A	-	-	MVA HIV-B	築壓夢觸遞壓構遞網夢(廠顧糧製鏇夢獵餘齋鏇) = 鹹構簾蓋觸獵願憲壓壓網鬱衊窪壓築繭構鑰獵 (醖範構鬱膚膚範襯網壓 )	-	2017-01-01
				LIPO-5	築壓夢觸遞壓構遞網夢(廠顧糧製鏇夢獵餘齋鏇) = 醖膚構鬱選構簾鬱憲鑰網鬱衊窪壓築繭構鑰獵 (醖範構鬱膚膚範襯網壓 )