Delving into the Latest Updates on VRC-HIVADV014-00-VP with Synapse

Overview

Basic Info

Drug Type

Recombinant vector vaccine, Prophylactic vaccine

Synonyms

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

+ [3]

Target

HIV-1 gag x HIV-1 pol

Mechanism

HIV-1 gag inhibitors(HIV-1 gag inhibitors), HIV-1 pol inhibitors(Human immunodeficiency virus type 1 protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

GenVec, Inc.

Active Organization-

Inactive Organization

National Institute of Allergy & Infectious Diseases

Vaccine Research Center

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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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....

Start Date17 Jun 2011

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT00955006

/ CompletedPhase 1IIT

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.

Start Date01 May 2011

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT01159990

/ CompletedPhase 1IIT

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.

Start Date01 Jan 2011

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with VRC-HIVADV014-00-VP

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100 Translational Medicine associated with VRC-HIVADV014-00-VP

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100 Patents (Medical) associated with VRC-HIVADV014-00-VP

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10

Literatures (Medical) associated with VRC-HIVADV014-00-VP

01 Aug 2020·VaccineQ3 · MEDICINE

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

Q3 · MEDICINE

Article

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

08 Oct 2019·The Journal of infectious diseasesQ2 · MEDICINE

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

Q2 · MEDICINE

Article

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

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.

01 Mar 2015·The lancet. HIVQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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 Deals associated with VRC-HIVADV014-00-VP

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	US	National Institute of Allergy & Infectious Diseases	01 Sep 2005
HIV Infections	Phase 2	BR	National Institute of Allergy & Infectious Diseases	01 Sep 2005
HIV Infections	Phase 2	HT	National Institute of Allergy & Infectious Diseases	01 Sep 2005
HIV Infections	Phase 2	JM	National Institute of Allergy & Infectious Diseases	01 Sep 2005
HIV Infections	Phase 2	ZA	National Institute of Allergy & Infectious Diseases	01 Sep 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00865566 (CTgov)	Phase 2	HIV Infections	2,504	recombinant DNA plasmid vaccine+DNA plasmid vaccine+Recombinant adenoviral serotype 5 (rAD5) vector vaccine (Vaccine)	shenytxddf(zfdboeloqt) = plxfdigsvz aozdfjtrep (fvdwkqxqij, mjxgjrgmjf - cthdwruhne) View more	-	27 Feb 2019
				placebo+DNA vaccine (Placebo)	shenytxddf(zfdboeloqt) = uwxijmwduw aozdfjtrep (fvdwkqxqij, dppxusdhuc - rjlkfizbij) View more
NCT00976404 (Pubmed \| Lancet HIV) Manual	Phase 2	HIV Infections	28	raltegravir+maraviroc+VRC-HIVDNA016-00-VP	hozgvyuoln(hjsxvbvxfh) = 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. bzrdzqgozm (wegsuapooj )	Negative	01 Mar 2015
				raltegravir+maraviroc
NCT00976404 (EraMune02, CTgov)	Phase 2	HIV Infections	28	ART intensification (maraviroc)+ART intensification (raltegravir) (Maraviroc + Raltegravir Intensification)	ltllnueqeb(jgksacrxpp) = zwchxskwqs mnhzziufml (zmdnrxmdyb, ikfkeuflui - ckwmswixyv) View more	-	12 Sep 2014
				DNA prime-boost+HIV-rAd5 vaccine+ART intensification (maraviroc)+ART intensification (raltegravir) (Maraviroc + Raltegravir Intens. Plus DNA + HIV-rAd5 Vaccine)	ltllnueqeb(jgksacrxpp) = fiohcxuydd mnhzziufml (zmdnrxmdyb, zqdbbrwjrx - swxguiwsfb) View more
NCT00083330 (Pubmed \| J Infect Dis)	Phase 1	HIV Infections	-	Vaccine at dose level 10^9 particle units	yipjrygxlq(xipfafwqnd) = uhjusrlniw kiqsphvitg (ylwbnmuwxe )	-	15 Dec 2006
				Vaccine at dose level 10^10 particle units	yipjrygxlq(xipfafwqnd) = czeylysdzt kiqsphvitg (ylwbnmuwxe )