A Phase I/IIa Clinical Trial of HIV-1 Vaccines pSG2.HIVconsv DNA, MVA.HIVconsv and Ad35-GRIN in Combined Regimens in Healthy HIV-1/2-negative Adults in Nairobi.

The study is part of a long-term aim to develop an effective HIV-1 vaccine and will evaluate safety and immunogenicity of vaccines focusing T cell responses on the conserved region of the HIV-1 proteome. The vaccines used are pSG2.HIVconsv DNA (D), MVA.HIVconsv (M) and Ad35-GRIN (A), delivered in regimens AM, DDDAM and DeDeDeAM, where e indicates electroporation.

开始日期2014-03-01

申办/合作机构

University of Oxford

[+4]

NCT01496989 / Completed临床1期IIT

A Phase 1 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate Safety and Immunogenicity of a Multiantigen HIV (HIV-MAG) pDNA Vaccine With or Without Human IL-12 pDNA GENEVAX® IL-12) and Ad35-GRIN/ENV Vaccine in HIV-Uninfected, Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability and immunogenicity of multiantigen HIV (HIV-MAG) plasmid DNA (pDNA) vaccine co-administered with recombinant human IL-12 pDNA (GENEVAX® IL-12) followed or preceded by recombinant Ad35-GRIN/ENV HIV vaccine in low-risk for HIV-uninfected healthy adults.

开始日期2011-12-01

申办/合作机构

International AIDS Vaccine Initiative, Inc.

[+2]

NCT00851383 / Completed临床1期IIT

A Phase I Placebo-controlled, Double-blinded (in Terms of Vaccine or Placebo), Randomized Dose-escalation Trial to Evaluate the Safety and Immunogenicity of Ad35-GRIN/ENV HIV Vaccine in Healthy Adult Volunteers. (IAVI B001)

The purpose of this study is to evaluate the safety and immunogenicity of Ad35-GRIN/ENV HIV vaccine and Ad35-GRIN HIV vaccine administered intramuscularly at 0 and 6 months.

开始日期2009-03-01

申办/合作机构

International AIDS Vaccine Initiative, Inc.

[+1]

100 项与 Ad35-GRIN/ENV 相关的临床结果

登录后查看更多信息

100 项与 Ad35-GRIN/ENV 相关的转化医学

登录后查看更多信息

100 项与 Ad35-GRIN/ENV 相关的专利（医药）

登录后查看更多信息

项与 Ad35-GRIN/ENV 相关的文献（医药）

PLoS ONE3区 · 综合性期刊

Heterologous Prime-Boost Regimens Using rAd35 and rMVA Vectors Elicit Stronger Cellular Immune Responses to HIV Proteins Than Homologous Regimens

3区 · 综合性期刊

ArticleOA

作者: Eddy Sayeed ; Anais Valencia-Micolta ; Victoria R. Polonis ; Josephine H. Cox ; Vicky Lo ; Jean-Louis Excler ; Merlin L. Robb ; Doris Thelian ; Jerome H. Kim ; Silvia Ratto-Kim ; Patricia L. Earl ; Nelson L. Michael ; Mary A. Marovich ; Jeffrey R. Currier ; Bernard Moss

We characterized prime-boost vaccine regimens using heterologous and homologous vector and gene inserts. Heterologous regimens offer a promising approach that focuses the cell-mediated immune response on the insert and away from vector-dominated responses. Ad35-GRIN/ENV (Ad35-GE) vaccine is comprised of two vectors containing sequences from HIV-1 subtype A gag, rt, int, nef (Ad35-GRIN) and env (Ad35-ENV). MVA-CMDR (MVA-C), MVA-KEA (MVA-K) and MVA-TZC (MVA-T) vaccines contain gag, env and pol genes from HIV-1 subtypes CRF01_AE, A and C, respectively. Balb/c mice were immunized with different heterologous and homologous vector and insert prime-boost combinations. HIV and vector-specific immune responses were quantified post-boost vaccination. Gag-specific IFN-γ ELISPOT, intracellular cytokine staining (ICS) (CD107a, IFN-γ, TNF-α and IL-2), pentamer staining and T-cell phenotyping were used to differentiate responses to inserts and vectors. Ad35-GE prime followed by boost with any of the recombinant MVA constructs (rMVA) induced CD8+ Gag-specific responses superior to Ad35-GE-Ad35-GE or rMVA-rMVA prime-boost combinations. Notably, there was a shift toward insert-focus responses using heterologous vector prime-boost regimens. Gag-specific central and effector memory T cells were generated more rapidly and in greater numbers in the heterologous compared to the homologous prime-boost regimens. These results suggest that heterologous prime-boost vaccination regimens enhance immunity by increasing the magnitude, onset and multifunctionality of the insert-specific cell-mediated immune response compared to homologous vaccination regimens. This study supports the rationale for testing heterologous prime-boost regimens in humans.

PLoS ONE3区 · 综合性期刊

A Phase I Double Blind, Placebo-Controlled, Randomized Study of a Multigenic HIV-1 Adenovirus Subtype 35 Vector Vaccine in Healthy Uninfected Adults

3区 · 综合性期刊

ArticleOA

作者: Lorna Clark ; Sabrina Welsh ; Tony Tarragona-Fiol ; Peter Hayes ; James Ackland ; Josephine H. Cox ; Michael C. Keefer ; Burc Barin ; Jill Gilmour ; Dilbinder Gill ; Lottie Hachaambwa ; Jakub Kopycinski ; Catherine A. Bunce ; Eddy Sayeed ; Wendy Komaroff ; Emmanuel Cormier ; Patricia Fast ; Devika Zachariah ; Christine M. Hay ; Marloes Naarding ; Natalia Fernandez ; Kelley Loughran ; Jean-Louis Excler ; Hannah Cheeseman ; Michelle Cashin-Cox

BACKGROUNDWe conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults.METHODSAd35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×10(9) (A), 2×10(10) (B), 2×10(11) (C), or Ad35-GRIN 1×10(10) (D) viral particles.RESULTSNo vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 10(6) PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination.CONCLUSION/SIGNIFICANCEAd35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination. T-cell responses were broad and polyfunctional.TRIAL REGISTRATIONClinicalTrials.gov NCT00851383.

PLOS ONE3区 · 综合性期刊

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

3区 · 综合性期刊

ArticleOA

作者: Voss, Gerald ; Barin, Burc ; Fast, Patricia ; Lombardo, Angela ; Mpendo, Juliet ; Anas, Kamaal ; Sayeed, Eddy ; Chomba, Elwyn ; Zachariah, Devika ; Collard, Alix ; Hayes, Peter ; Laufer, Dagna ; Stevens, Gwynn ; Ruzagira, Eugene ; Omosa-Manyonyi, Gloria ; Dally, Len ; Clark, Lorna ; Cormier, Emmanuel ; Priddy, Frances ; Syvertsen, Kristen ; Cox, Josephine ; Koutsoukos, Marguerite ; Bourguignon, Patricia ; Kilembe, William ; Gilmour, Jill ; Roman, François ; Ackland, Jim

BACKGROUNDSequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses.METHODSIn a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured.RESULTSThe vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration.CONCLUSIONCo-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.TRIAL REGISTRATIONClinicalTrials.gov NCT01264445.

100 项与 Ad35-GRIN/ENV 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
获得性免疫缺陷综合征	临床2期	肯尼亚	Ichor Medical Systems, Inc.	2014-03-01
HIV感染	临床2期	美国	International AIDS Vaccine Initiative, Inc.	2009-03-01