Initiative canadienne de vaccin contre le VIH

Initiative canadienne de vaccin contre le VIH - Governement du Canada

2008 Subvention catalyseur

Subvention catalyseur : Recherche sur des vaccins contre le VIH/sida (Initiative can.)--

Concours année: 200811

Chercheur principal

Établissement

Titre du project

Montant

Équipement

Durée

GRANT, Michael D

Memorial University of Newfoundland

Heteroclitic Peptides to Increase Human Immunodeficiency Virus-specific CD8+ T cell Interleukin-2 Production

$100,000

1an

Résumé

Vaccines administered to individuals already infected with a pathogen are called thrapeutic vaccines. In chronic human immunofdeficiency virus (HIV) infection,therapeutic vaccines stimulate pre-existing and new immunity against HIV. If boosted immunity more effectively suppresses HIV replication, this could offer broader treatment options where antiretroviral drugs are not widely available and reduce dependence on antiretroviral drugs elsewhere. While therapeutic vaccines tend to focus on conserved portions of HIV or sequences known to be present in the infected individuals, we plan to test sequence variants that arise rarely in nature. Our hypothesis is that the immune system rapidly selects against variants that are more immunogenic than common sequences. Therefore, such sequences as rarely occur naturally in HIV may be more effective in therapeutic vaccines than the common sequences currently employed. Our research project aims to demonstrate this possibility and identify HIV peptide sequence variants with this characteristic for inclusion in future therapeutic HIV vaccines.

JOLICOEUR, Paul

Institut de recherches cliniques de Montréal

Dissecting the mechanisms of protection by attenuated Nef-deleted HIV vaccine

$100,000

1an

Résumé

The development of a vaccine against HIV-1 represents the best hope of controlling the worldwide AIDS epidemics. To date, no vaccine has been shown to be clinically useful. However, in monkeys, an attenuated SIV (simian immunodeficiency virus) belonging to the same family of viruses and causing a similar disease as HIV-1, has been shown to be a very efficient vaccine against the challenging SIV. There is a general concensus that this represents the best available and the most potent vaccine against SIV. It is presumed that a similarly attenuated HIV-1 would also be very efficient as a vaccine. However, the mechanisms by which this attenuated SIV vaccine works do not seem to be through known immune responses (such as antibodies). Rather, protection is postulated to be mediated by evolutionary conserved mechanisms, designated innate immunity. Although such an attenuated SIV/HIV virus is dangerous and would never be used to vaccinate humans, knowing how it works would be very useful to design an HIV vaccine. The aim of our project is to study the mechanisms of protection by an attenuated HIV and SIV, in order to get insights on how to design a non-dangerous and potent HIV vaccine. We intend to carry out these experiments in the mouse because the same innate immunity as in monkeys and humans is likely to be effective, if indeed, this represents the mode of protection. Moreover, mice offer strong genetic tools to dissect this protective effect. Transgenic mice expressing the attenuated HIV or SIV will be challenged with HIV or SIV, in order to determine whether protection also arise in mice and by which mechanism.

LANGLOIS, Marc-Andre

Université Laval

Promoting innate immunity to HIV infection by vaccine delivery of third generation RNA analogs

$100,000

1an

Résumé

Infection by the human immunodeficiency virus (HIV) can lead to a progressive deterioration of the body's immune system. AIDS (Acquired Immunodeficiency Syndrome) represents the stage when a HIV-infected individual's life is threatened by common pathogens that are normally destroyed by the immune system of healthy individuals. HIV is a retrovirus that has evolved to circumvent the human immune system in such ways that no cure or vaccine has yet been successfully developed. One of the virus' survival strategies is to cripple conventional adaptive immune responses that are essential for the effectiveness of most vaccines because the cells of the immune system themselves are its target. Nevertheless, there are several endogenous factors that can protect humans against the spread of HIV infection. One of these antiviral factors is a protein called APOBEC3G that is part of the innate component of the immune system. This protein can bind and heavily mutate HIV DNA, ultimately leading to the inactivation and destruction of the virus. Unfortunately, HIV encodes a protein called Vif that is dedicated to specifically induce the degradation of APOBEC3G. The overall aim of this catalyst grant proposal is to validate a new Vif-inhibiting technology that could lead to the development of a vaccine that could induce the inactivation infectious HIV particles in HIV/AIDS patients and also promote the elimination of HIV infected cells by recruiting the intrinsic antiviral properties of the innate immune system.

SNIDER, Denis P

McMaster University

Functional correlate of mucosal antibody response to HIV infection in blood.

$100,000

1 an

Résumé

Most infections with HIV worldwide are sexually transmitted and women are the most frequently infected. In order to protect against HIV infection and AIDS, vaccines must be effective at blocking entry of the virus. In sexual transmission, HIV enters through the mucosal surfaces of the body. These surfaces can respond with a specific type of antibody, the IgA type. Thus, when developing new HIV vaccines, we must be able to measure the Montant and quality of mucosal IgA antibody against HIV. Studies have shown that women who are able to resist HIV infection have IgA antibodies against HIV, while those that become infected have little or no IgA. Unfortunately, many such studies have conflicting results or are hampered by the difficulty in sampling and testing for these IgA antibodies, using fluid samples from the mucosal surfaces. A test in blood would be much more simple, reliable, and useful. We propose to use the circulating immune cells in blood responsible for IgA antibody production, as a reliable means to measure the Montant and quality of mucosal IgA antibody against HIV. In our proposal, we will be able to determine if IgA antibody was produced, how much response is evident, and how well the IgA antibody can inhibit the virus. We will look at HIV resistant and HIV infected people to see if any differences exist in mucosal IgA antibodies, obtained from the blood cells. These studies will provide valuable data and will prove the feasibility of measuring mucosal IgA responses, using blood samples.

TREMBLAY, Michel J

Université Laval

A new human cell experimental system for evaluating prototype HIV-1 vaccines

$100,000

1 an

Résumé

The development of an effective vaccine against human immunodeficiency virus type-1 (HIV-1) has proven an enormous scientific challenge that is partly due to the lack of a suitable experimental cell system to investigate protective immune responses to HIV-1. Previous studies have shown that secondary lymphoid organs constitute preferred anatomical sites for HIV-1 replication and propagation. Given that secondary lymphoid organs are essential for the development of effective immune responses, we are proposing to test whether human lymphoid tissue cultured ex vivo could represent an appropriate experimental cell system to critically evaluate candidate HIV-1 vaccines.

2008 Subvention de fonctionnement

Initiative Canadienne Vaccin contre VIH - Annonce de priorités

Concours année: 200809

Chercheur principal

Établissement

Titre du project

Montant

Équipement

Durée

BERNARD, Nicole F

The Research Institute of the McGill University Health Centre

The functional profile of NK cells in HIV exposed uninfected subjects: Association with carriage of NK receptor-HLA ligand genotypes.

$440,604

3 ans

Résumé

Natural killer (NK) cells are a key player in innate immunity to viruses such as HIV. NK cells can recognize virus infected cells very early after infection. They do so through cell surface receptors that recognize a cell surface molecule called HLA present on most cells in the body, including those that HIV enters in a new infection. The NK receptors and HLA molecules have many variants that differ from one person to another and influence the potency of NK cell activation when these cells see a virus infected target. Our previous work identified variants of NK receptors and HLA that are present more frequently in people who remain uninfected despite exposure to HIV (exposed uninfected or EU subjects) than in HIV susceptible individuals. There results led us to hypothesize that expressing the kind in NK receptor associated with protection from infection leads to activation of NK cells to either more readily kill HIV infected cells or prevent HIV from replicating and spreading. In this project we will study the anti-viral functions of NK cells from individuals carrying NK receptor HLA combinations associated with protection from HIV infection compared to that from subjects not carrying these combinations. Understanding how EUs are protected from infection is important because it may provide clues on how to manipulate the immune system in the context of vaccines to reduce the risk of HIV infection.

CEN, Shan

Jewish General Hospital (Montreal)

The potential of APOBEC3G in the development of a novel anti-HIV-1 therapeutic.

$327,993

3 ans

Résumé

APOBEC3G is a host factor that is able to inhibit HIV-1 replication. A HIV-1 protein, so-called Vif, can protect the virus from the attack of APOBEC3G by binding to APOBEC3G and subsequently destroying it. Understanding the mechanism of how Vif protects HIV-1 from the inhibition by APOBEC3G may lead us to develop a novel therapeutic strategy for HIV-1 infection. The objective of this work is to explore the mechanism by which Vif abolishes anti-HIV activity of APOBEC3G.

FOWKE, Keith R

University of Manitoba

The effect of the CD4 pathogenicity island on HIV susceptibility and disease progression

$663,050

5 ans

Résumé

As humans we all share the same set of gene, however, we all possess slightly different versions of those gene and that is what makes us all unique as individuals. These genetic differences, called polymorphisms, also have been shown to be associated with differing susceptibility to disease, such as HIV. Our lab has previously demonstrated a link between increased susceptibility to HIV infection and a particular version of the gene that encodes the main host protein that HIV uses to enter into a cell, called CD4. Recent studies from our lab have shown that the genes that surround CD4 could also be linked to altered HIV susceptibility. We have termed this group of genes the CD4 pathogenicity island and this proposal seeks to explore the genetic linkages between these genes and also determine at a molecular level how they affect susceptibility to HIV infection. These studies could lead to be better understanding of the molecular events necessary to HIV to infect a cell which would provide a foundation for further anti-HIV drug development.

LIANG, Chen

Jewish General Hospital (Montreal)

Studying the antiviral activity of bone marrow stromal cell antigen 2 and the countering mechanism from HIV-1 Vpu

$721,347

5 ans

Résumé

Human immunodeficiency virus type 1 (HIV-1) has claimed the lives of 25 million people since the beginning of the AIDS epidemic in the early 1980s and endangers the life of 33 million infected individuals. Finding an effective treatment or a cure for this deadly virus is the goal of AIDS research. The currently available antiretroviral drugs are potent enough to lower the viral load in patient below the detection level and thus can extend the patient's life for more than 25 ans on average. Yet, the inevitable appearance and circulation of multi-drug resistance HIV-1 strains quickly exhausts the effectiveness of these HIV-1 inhibitors. Without an HIV-1 vaccine in hand, developing new antiretrovirals is essential to control this epidemic. Research proposed in this grant application is aimed to study one recently host factor named bone marrow stromal cell antigen 2 (BST2) that potently block HIV-1 production when viral Vpu is not expressed. Understanding how BST2 restricts HIV-1 production and how Vpu counteracts BST2 is expected to reveal new strategies for developing novel HIV-1 therapeutic approaches.

TREMBLAY, Michel J

Université Laval

A comparative immunogenicity study of HIV-1 Pr160Gag-Pol virus-like particles bearing gp120, CD40L and/or TLR5 agonist flagellin

$391,824

3 ans

Résumé

Despite current progress, the development of a safe and effective HIV-1 vaccine is still a major concern and an immense challenge. It has been previously demonstrated that virus-like particles (VLPs) are superior to conventional protein immunogens in the activation of immune responses. Unfortunately, HIV-1 has been reported to display a low immunogenicity by itself. To improve immunogenicity of HIV-1-based VLPs, we are proposing to incorporate constituents that can stimulate immune cells into VLPs. We propose that this experimental strategy could enhance and broaden immune responses, which are required for controlling HIV-1 infection.

2008 Subvention de voyage

Recherche sur des vaccins contre le VIH/sida--

Résultats du concours (Septembre 2008 Competition - 200809VVG)

Chercheurs principaux

Institut de recherche

Titre du projet

Montant moyenne annuelle

Durée

BALL, Terry B

University of Manitoba

Travel support to attend the AIDS Vaccine 2008 Partnership Development Forum in Cape Town, South Africa

$9,500

3 Mois

MACDONALD, Kelly S

Mount Sinai Hospital (Toronto)

Comprehensive Development and Evaluation of Herpes Virues as HIV Vaccine Vectors with Special Reference to Suitability and Application in Sub-Saharan Africa

$8,375

3 Mois

MOORE, David M

University of British Columbia

Canadian African Prevention Trials Network Travel Grant

$12,300

3 Mois

NEWMAN, Peter A

University of Toronto

Travel support to attend AIDS Vaccine 2008 Partnership Development Forum

$8,579

3 Mois

OSTROWSKI, Mario A

University of Toronto

Development of Novel Vaccine strategies against HIV-1 infection

$2,000

3 Mois

WILLER, David O

Mount Sinai Hospital (Toronto)

Herpes viruses as re-activating Vaccine Vectors: Protective Efficacy of a Varicella Zoster-HIV Vaccine in the SIV Macaque model"

$7,537

3 Mois

Pour accéder aux résultats du concours a l`égard de recherche sur des vaccins contre le VIH/sida veuillez visitez le site web: http://www.cihr-irsc.gc.ca/f/37722.html

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