In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
A successful vaccine prevents infection. For HIV infection all candidate vaccines thus far have failed. From the many HIV-1 infected individuals there are a very small percentage that do not progress to disease. For these infected subjects we hypothesise that their immune responses are much better preserved and hence they will have stronger antibody responses. We have geared up our laboratory to characterise these strong antibodies and use them in making a better HIV-1 vaccine.
Mucosal Human Immunodeficiency Virus Vaccine Late Pre-clinical Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$575,315.00
Summary
Despite many candidate vaccines entering clinical development for protection against HIV, none has yet been successful. This proposal centres on late preclinical development for a novel mucosal vaccine strategy for HIV, which combines a preclinically-proven approach to generating strong T cell immune responses, with an existing approach to generating broadly neutralising antibody responses to HIV. Proof of synergy between these approaches will lead directly to clinical development.
Development Of Chimeric Hepatitis B Virus Like Particles As A Vaccine Delivery Platform For Multiple HIV-1 Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$139,500.00
Summary
The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involv ....The small envelope protein of hepatitis B virus (HBsAg) can self-assemble into highly organised viruslike particles with about 150 HBsAg-proteins forming a virus-like particle (VLP). VLPs induce an effective immune response, mainly against the exposed major antigenic site, the hydrophilic ‘a’- determinant region. To create a novel HBsAg-specific vaccine vector, foreign epitopes were inserted into the major antigenic site allowing surface orientation of the inserted sequence. Pilot studies involving the vaccination of mice with VLPs containing an epitope derived from the AIDS-virus (human immunodeficiency virus 1, HIV-1) or various hepatitis C virus-specific epitopes resulted in high titre antibody responses. This project aims for the development of a multi-component vaccine targeting a non-structural HIV-1 protein and therefore, avoiding the selective pressure directed against the structural proteins. The non-structural HIV-1 tat-protein is a multi-functional protein with an extracellular mode to sensitise uninfected cells for HIV-1 infection and to reactivate HIV-1 from quiescently infected cells. The use of eight tat-sequences is sufficient to provide coverage against 99% of HIV-1 sequences. We will develop hybrid particles that are composed of different sets of chimeric HBsAg proteins each containing a distinct tat-epitope. With this application, we aim to develop hybrid particles for the delivery of the complete set of tat-epitopes. The hybrid particles will be used for vaccination studies in mice, and the antibodies assessed by an in-vitro assay. This will lead to the development of a therapeutic and-or prophylactic HIV-1 vaccine, which could be used either for mass immunisation or in support of combination drug therapy and would have all the cost and production advantages of the widely used hepatitis B vaccine.Read moreRead less
The Influence Of HIV On T Cell Function And Application To Vaccine Design.
Funder
National Health and Medical Research Council
Funding Amount
$427,899.00
Summary
Development of a safe, effective vaccine remains the only viable means of abating the human immunodeficiency virus (HIV) pandemic in the long term. Scientists must develop a vaccine that could protect against many diverse HIV strains worldwide. This research aims to understand the ways in which HIV mutates to avoid human immune responses in order to determine how best to design a vaccine. The findings could be applied to other infectious diseases for which vaccines are also needed.
Immunopathogenesis And Manipulation Of The HIV Reservoir
Funder
National Health and Medical Research Council
Funding Amount
$494,732.00
Summary
Kelleher is a Clinical immunologist with a globally recognised, sustained track record of translational research which has impacted both on our understanding of HIV immunopathogenesis and on the way HIV infection is treated. He will conduct a series of studies that encompass basic scientific techniques through to pivotal pre-clinical and clinical studies that will provide a pathway towards control of HIV-infection without daily therapy.
HIV is one of the highest public health priorities of our time. Traditional vaccines have been unsuccessful highlighting the need for alternative approaches to HIV vaccine design. We propose to modify a novel technology developed initially for targeted drug delivery, termed “capsules”, for the purpose of inducing an immune response. This is a generic technology with applications for other infectious diseases and cancer and brings together disparate disciplines of nanochemistry and immunology.
Evaluation Of Immune Correlates For Virus-specific CD8+ T Cells Following Prime-boost Vaccination
Funder
National Health and Medical Research Council
Funding Amount
$397,889.00
Summary
This project will use cutting-edge technology to evaluate the quality of virus-specific white blood cells generated following vaccination. Clinically relevant vaccination strategies will be analysed in a well characterised mouse model of infection to produce correlates associated with protective vaccine efficacy, particularly in an immunosupressed setting. This will lead to more focused research and ultimately the development of prophylactic and therapeutic HIV vaccines.
Control Of Combined Simian-human Immunodeficiency Virus Infection Utilising NK Cells Mediating Antigen-specific Antibody Dependent Cellular Cytotoxicity - A Novel Vaccine Modality
Funder
National Health and Medical Research Council
Funding Amount
$432,587.00
Summary
Recently, progress was made in developing a vaccine against HIV. Our laboratory was selected to join a global collaboration trying to elucidate the key to this success. Attention has focused on non-neutralizing antibodies and our laboratory has developed a unique expertise in detecting such immune responses. This research will define, purify and manufacture these antibodies and test their ability to prevent HIV in animals with the ultimate aim of producing a vaccine for human use.