VRC-HIVADV014-00-VP(VRC-HIVADV014-00-VP) - 药物靶点：HIV-1 gag x HIV-1 pol_专利_临床

概要

基本信息

药物类型

重组载体疫苗、预防性疫苗

别名

AD5HIV-ENVA、HIV adenovector serotype Ad5 vaccine、rAd5 gag-pol/env A/B/C vaccine

+ [3]

靶点

HIV-1 gag x HIV-1 pol

作用机制

HIV-1 gag抑制剂(HIV-1病毒gag蛋白抑制剂)、HIV-1 pol抑制剂(人类免疫缺陷病毒1型蛋白酶抑制剂)

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症-

非在研适应症

HIV感染

原研机构

GenVec, Inc.

在研机构-

非在研机构

National Institute of Allergy & Infectious Diseases

Vaccine Research Center

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

22

项与 VRC-HIVADV014-00-VP 相关的临床试验

NCT01386489

/ Completed临床1期IIT

VRC 016: A Phase 1b Open-Label, Randomized Clinical Trial to Evaluate Early Innate and Adaptive Immune Responses to the Investigational HIV-1 Vaccines: VRC-HIVADV014-00-VP and VRC-HIVDNA016-00-VP in Ad5 Seronegative Healthy Adults

Background:
The primary focus of the Vaccine Research Center (VRC) at the NIH is to develop vaccines for HIV/AIDS. The main purpose of this study is to look in detail at the body s immune response to two experimental HIV vaccines currently in development at the VRC. One is known as the rAd5 vaccine and the other is known as the DNA vaccine. These vaccines are made with pieces of manufactured DNA. They do not contain live or killed HIV. It is impossible for study vaccines to give you HIV and they cannot cause you to give HIV to someone else. Both of these experimental vaccines have been given to people before in other research studies. They have not been approved for treating or preventing HIV infection.
Purpose:
The main purpose of this study is to look in detail at the body s immune responses after the experimental HIV vaccines are given and to assess safety of the study vaccines.
Eligibility:
Healthy volunteers between the ages of 18 and 50 who are not infected with HIV and who meet the eligibility requirements.
Design:
Participants will be screened with a medical history (including questions about sexual history and drug use), physical exam, and blood tests.
The study will have two groups:
One group will receive one injection of the rAd5 vaccine, and have 8 clinic visits over 3 months.
The second group will have three injections of the DNA vaccine, one injection of the rAd5 vaccine, and have 12 clinic visits over 6 months.
All participants will be asked to provide blood and body fluid samples for testing during the study.
Payment for participation will be provided....

开始日期2011-06-17

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT00955006

/ Completed临床1期IIT

A Phase 1b Clinical Trial to Evaluate Mucosal Immune Responses to a DNA Plasmid Vaccine Prime Followed by an HIV-1 Adenoviral Vector Boost in Healthy Adenovirus Type 5 Seronegative HIV-1-uninfected Adults

The purpose of the study is to determine the safety of mucosal immune responses to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.

开始日期2011-05-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT01159990

/ Completed临床1期IIT

A Randomized, Double Blind Phase 1b Trial to Examine the Influence of Antigenic Competition on the Immunogenicity of HIV-1 Gag/Pol: A Comparison of rAd5 Gag/Pol Env A/B/C to rAd5 Gag/Pol

HIV vaccines are designed to create an immune response to certain components of the HIV virus called peptides. Previous research indicates that one peptide, called Gag, may be particularly important for stimulating an immune response to HIV. Many vaccines being studied combine multiple peptides, but including other peptides may weaken the body's response to Gag. This study will test whether a vaccine that targets Gag and another peptide called Env is better than a vaccine without Env at causing an immune response to Gag.

开始日期2011-01-01

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 VRC-HIVADV014-00-VP 相关的临床结果

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100 项与 VRC-HIVADV014-00-VP 相关的转化医学

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100 项与 VRC-HIVADV014-00-VP 相关的专利（医药）

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8

项与 VRC-HIVADV014-00-VP 相关的文献（医药）

2020-08-01·Vaccine3区 · 医学

Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine

3区 · 医学

Article

作者: Shao, Jason ; Maenza, Janine ; Rosa, Stephen C De ; Curlin, Marcel E ; Corey, Lawrence ; Keefer, Michael C ; Allen, Mary ; Edlefsen, Paul T ; Novak, Richard M ; Morgan, Cecilia ; Diaz, Gabriela ; Mayer, Kenneth H ; Buchbinder, Susan ; Duerr, Ann

BACKGROUND:

Vaccine-induced mucosal immune responses may be critical for protection against HIV infection, but may also result in short or long-term changes that enhance susceptibility to infection in some individuals, such as those with baseline seroreactivity to vaccine vector antigens. We examined cellular immune responses in blood and gut mucosal tissue roughly two years following vaccination with placebo or the Step study vaccine MRKAd5/HIV-1.

METHODS:

Participants vaccinated with either placebo or MRKAd5/HIV-1 during participation in HVTN 071, and HVTN 502/Merck 023 underwent phlebotomy and colonic mucosal biopsies via flexible sigmoidoscopy at two timepoints roughly six months apart. After isolation of mononuclear cells, we compared cellular phenotypes and intracellular cytokine responses in vaccine and placebo recipients with and without baseline serological reactivity to Ad5.

RESULTS:

Surface expression of activation and gut-homing markers were elevated on CD4 + and CD8 + gut mucosal mononuclear cells (GMMC) in comparison with PBMC (p < 0.01), but were not significantly affected by baseline Ad5 serostatus or receipt of MRKAd5/HIV-1. ICS responses to stimulation with vaccine antigens were of low frequency and magnitude. Ad5 vector responses were seen in vaccinees and baseline seropositive individuals. CD4 + responses to vector antigens were more common in GMMC than PBMC (p < 0.01) and CD8 + responses to HIV gag insert antigens were more frequent in Ad5 seropositive than Ad5 seronegative individuals (p = 0.03).

CONCLUSION:

Vaccination with the Ad5 vectored candidate HIV vaccine MRKAd5/HIV-1 does not lead to long-term changes in the activation state of mucosal CD4 + or CD8 + T lymphocytes regardless of baseline Ad5 serostatus. The findings of this study do not reveal a basis for enhanced susceptibility to HIV infection two years post vaccination.

2019-10-08·The Journal of infectious diseases2区 · 医学

HLA-I Associated Adaptation Dampens CD8 T-Cell Responses in HIV Ad5-Vectored Vaccine Recipients

2区 · 医学

Article

作者: Qin, Kai ; Cohen, Kristen W ; Sterrett, Sarah ; Files, Jacob ; Bansal, Anju ; De Rosa, Stephen C ; Boppana, Sushma ; Goepfert, Paul A ; Fiore-Gartland, Andrew

Abstract:

HLA-I–associated human immunodeficiency virus (HIV) adaptation is known to negatively affect disease progression and CD8 T-cell responses. We aimed to assess how HLA-I–associated adaptation affects HIV vaccine–induced CD8 T-cell responses in 2 past vaccine efficacy trials. We found that vaccine-encoded adapted epitopes were less immunogenic than vaccine-encoded nonadapted epitopes, and adapted epitope-specific responses were less polyfunctional than nonadapted epitope-specific responses. Along those lines, vaccine recipients with higher HLA-I adaptation to the Gag vaccine insert mounted less polyfunctional CD8 T-cell responses at the protein level. Breadth of response, which correlated with viral control in recipients who became infected, is also dampened by HLA-I adaptation. These findings suggest that HLA-I–associated adaptation is an important consideration for strategies aiming to induce robust CD8 T-cell responses.

2015-03-01·The lancet. HIV1区 · 医学

Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a multicentre randomised clinical trial

1区 · 医学

Article

作者: Timothy J Wilkin ; Robert L Murphy ; Lambert Assoumou ; Richard A Koup ; Dominique Costagliola ; Christine Katlama ; Chad J Achenbach ; Vincent Calvez ; Steven G Deeks ; Sidonie Lambert-Niclot ; Joseph P Casazza ; Baiba Berzins ; Brigitte Autran

BACKGROUND:

Achievement of a cure for HIV infection might need reactivation of latent virus and improvement of HIV-specific immunity. As an initial step, in this trial we assessed the effect of antiretroviral therapy intensification and immune modulation with a DNA prime and recombinant adenovirus 5 (rAd5) boost vaccine.

METHODS:

In this multicentre, randomised, open-label, non-comparative, phase 2 clinical trial, we enrolled eligible adults 18-70 years of age with chronic HIV-1 infection on suppressive antiretroviral therapy with current CD4 count of at least 350 cells per μL and HIV DNA between 10 and 1000 copies per 10(6) peripheral blood mononuclear cells. After an 8 week lead-in of antiretroviral intensification therapy (standard dose raltegravir and dose-adjusted maraviroc based on baseline antiretroviral therapy), patients were randomly assigned (1:1) to receive antiretroviral therapy intensification alone or intensification plus injections of HIV DNA prime vaccine (4 mg VRC-HIVDNA016-00-VP) at weeks 8, 12, and 16, followed by HIV rAd5 boost vaccine (10(10) particle units of VRC-HIVADV014-00-VP) at week 32. Randomisation was computer generated in permuted blocks of six and was stratified by study site. The primary endpoint was a 0·5 log10 or greater decrease in HIV DNA in peripheral blood mononuclear cells at week 56. This study is registered with ClinicalTrials.gov, number NCT00976404.

FINDINGS:

Between Nov 29, 2010, and Oct 28, 2011, we enrolled 28 eligible patients from three academic HIV clinics in the USA. After the 8 week lead-in of antiretroviral intensification therapy, 14 patients were randomly assigned to continue antiretroviral therapy intensification alone and 14 to intensification plus vaccine. Enrolled participants had median CD4 count of 636 cells per μL, median HIV DNA 170 copies per 10(6) peripheral blood mononuclear cells, and duration of antiretroviral therapy of 13 years. The median amount of HIV DNA did not change significantly between baseline and week 56 in the antiretroviral therapy intensification plus vaccine group. One participant in the antiretroviral therapy intensification alone group reached the primary endpoint, with 0·55 log10 decrease in HIV DNA in peripheral blood mononuclear cells. Both treatments were well tolerated. No severe or systemic reactions to vaccination occurred, and five serious adverse events were recorded during the study, most of which resolved spontaneously or were judged unrelated to study treatments.

INTERPRETATION:

Antiretroviral therapy intensification followed by DNA prime and rAd5 boost vaccine did not significantly increase HIV expression or reduce the latent HIV reservoir. A multifaceted approach that includes stronger activators of HIV expression and novel immune modulators will probably be needed to reduce the latent HIV reservoir and allow for long-term control in patients off antiretroviral therapy.

FUNDING:

Objectif Recherche Vaccin SIDA (ORVACS).

100 项与 VRC-HIVADV014-00-VP 相关的药物交易

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研发状态

10 条进展最快的记录,

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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	美国	National Institute of Allergy & Infectious Diseases	2005-09-01
HIV感染	临床2期	巴西	National Institute of Allergy & Infectious Diseases	2005-09-01
HIV感染	临床2期	海地	National Institute of Allergy & Infectious Diseases	2005-09-01
HIV感染	临床2期	牙买加	National Institute of Allergy & Infectious Diseases	2005-09-01
HIV感染	临床2期	南非	National Institute of Allergy & Infectious Diseases	2005-09-01

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临床结果

适应症

分期

评价

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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


NCT00865566 (CTgov)	临床2期	HIV感染	2,504	recombinant DNA plasmid vaccine+DNA plasmid vaccine+Recombinant adenoviral serotype 5 (rAD5) vector vaccine (Vaccine)	壓範鏇選構憲醖廠繭膚(鹹鹹鏇膚鏇繭廠醖艱蓋) = 製範製廠齋艱簾積製鏇醖遞簾醖蓋艱鏇鬱願鹽 (遞顧簾鏇遞襯壓鏇醖築, 願鏇壓繭簾鑰築鬱襯遞 ~ 簾齋網構顧製窪簾築鏇) 更多	-	2019-02-27
				placebo+DNA vaccine (Placebo)	壓範鏇選構憲醖廠繭膚(鹹鹹鏇膚鏇繭廠醖艱蓋) = 顧築選觸蓋遞繭衊壓顧醖遞簾醖蓋艱鏇鬱願鹽 (遞顧簾鏇遞襯壓鏇醖築, 鹹獵廠簾鹹選觸選構壓 ~ 鹽簾膚淵積網築範製遞) 更多
NCT00976404 (Pubmed \| Lancet HIV) 人工标引	临床2期	HIV感染	28	raltegravir+maraviroc+VRC-HIVDNA016-00-VP	壓簾築願遞廠衊網遞網(鏇繭簾觸艱鬱齋鹽憲鑰) = One participant in the antiretroviral therapy intensification alone group reached the primary endpoint, with 0·55 log10 decrease in HIV DNA in peripheral blood mononuclear cells. 築憲襯壓衊選構顧顧醖 (築簾艱淵選蓋糧艱襯衊 )	不佳	2015-03-01
				raltegravir+maraviroc
NCT00976404 (EraMune02, CTgov)	临床2期	HIV感染	28	ART intensification (maraviroc)+ART intensification (raltegravir) (Maraviroc + Raltegravir Intensification)	餘艱艱鑰鹽襯繭襯壓鑰(簾醖選餘糧襯艱壓壓簾) = 積簾觸衊壓範醖獵鹽膚餘鑰衊壓範壓繭蓋鏇鑰 (顧齋築網獵齋醖顧築鏇, 蓋構顧範製鹹築範憲製 ~ 獵顧齋糧簾範夢獵網構) 更多	-	2014-09-12
				DNA prime-boost+HIV-rAd5 vaccine+ART intensification (maraviroc)+ART intensification (raltegravir) (Maraviroc + Raltegravir Intens. Plus DNA + HIV-rAd5 Vaccine)	餘艱艱鑰鹽襯繭襯壓鑰(簾醖選餘糧襯艱壓壓簾) = 廠壓糧鑰鹽鹽繭憲積顧餘鑰衊壓範壓繭蓋鏇鑰 (顧齋築網獵齋醖顧築鏇, 範淵積襯積廠餘窪繭淵 ~ 鹽繭艱廠窪鬱醖築範壓) 更多
Pubmed \| J Infect Dis	临床1期	HIV感染	-	Vaccine at dose level 10^9 particle units	艱糧壓廠餘淵構糧範鹽(蓋製窪積鬱衊襯衊遞鏇) = 齋蓋網顧鹹願鏇製憲衊簾鑰膚繭鏇製鹹鹹簾廠 (鹽鏇願構積簾艱襯構獵 )	-	2006-12-15
				Vaccine at dose level 10^10 particle units	艱糧壓廠餘淵構糧範鹽(蓋製窪積鬱衊襯衊遞鏇) = 糧網壓襯膚餘範簾選鹽簾鑰膚繭鏇製鹹鹹簾廠 (鹽鏇願構積簾艱襯構獵 )