Kent Laboratory
Overview of research projects | Recent publications
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Overview of Research Projects
An HIV vaccine is urgently needed. The Kent lab is working towards this goal.
The HIV pandemic continues to expand rapidly around the world, notably in the Asian-Pacific and Africa. Public health and economic burdens of HIV represents a major threat to regional and global security. Preventative strategies remain limited, and therapeutic options are restricted in both efficacy and implementation. The lack of an effective HIV vaccine is a catastrophic failure of our public health response to the epidemic.
Better strategies are needed to prevent HIV infection and disease. This requires an understanding of how HIV causes AIDS, including which immune responses control HIV replication and which contribute to disease. A better understanding of effective immunity will expand the pipeline to novel treatment and prevention strategies.
Despite the clear need, development of HIV-1 vaccines has proceeded for 20 years without success. HIV has a propensity to mutate to avoid immune responses and form latent reservoirs - these are formidable challenges to developing successful vaccines. There is a palpable sense in the HIV vaccine research community that fresh innovative ideas are needed. Quantum leaps away from existing paradigms will be needed to make large inroads into defining protective immunity to HIV-1.
To further understand how immune responses can control HIV, we have a series of projects involved in developing new assays to measure immunity and the effect these immune responses have on the virus. We have recently developed a new and exciting technique to measure antibody dependent cellular cytotoxicity (ADCC). We developed a very simple assay on small volumes of blood to measure ADCC responses and are now studying how useful it is in people with HIV and whether it forces the virus to mutate to escape this potentially important response. Although T cell immunity is effective against the virus, immune escape is a hallmark of effective T cell immunity. We have developed innovative techniques to measure immune escape variants very sensitively. This allows us to study the impact of these escape mutants and whether it can force the virus into a weakened state. We have become very interested in how immune responses target the envelope protein of the virus. Surprisingly, our data to date suggests that envelope specific T cell immunity has little impact on virus replication. We are now trying to understand how neutralising antibodies and T cell immunity against envelope could help corner the virus. We also have ongoing projects studying small but important lymphocyte populations such as regulatory T cells and NKT cells.
Our understanding of immune responses against the virus allows us to push on with developing novel vaccine technologies. In particular we have an exciting project studying nanoparticle vaccines where tiny capsules are loaded with vaccine antigens to protect them from degradation and target important immune cells that stimulate effective immunity. We are continuing to study aspects of overlapping peptide pulsed autologous cells (OPAL) as an effective therapeutic vaccine. We recently showed that this vaccine can delay AIDS. In addition we have exciting projects studying influenza recombinant vaccines. These flexible vaccine technologies allow us to refine our understanding of what will constitute effective immunity to HIV.
Selected Recent Publications
[See complete list of publications]
Loh L, Reece JC, Fernandez CS, Alcantara S, Center R, Howard J, Purcell DFJ, Balamurali M, Petravic J, Davenport MP, Kent SJ. Complexity of the inoculum determines the rate of reversion of SIV Gag CD8 T cell mutant virus and outcome of infection. PloS Pathogens, 2009;5(4): e1000378.
Fernandez CS, Chan AC, Kyparissoudis K, De Rose R, Godfrey DI, Kent SJ. Peripheral NKT cells in SIV-infected macaques. Journal of Virology, 2009; 83: 1617-1624.
Chung AW, Rollman E, Center RJ, Kent SJ, Stratov I. Rapid degranulation of NK cells following activation by HIV-specific antibodies. Journal of Immunology, 2009; 182: 1202-1210.
Peut V, Kent SJ. Substantial Envelope-specific CD8 T cell immunity fails to control SIV. Virology, 2009; 384: 21-27.
Mason RD, Alcantara S, Peut V, Loh L, Lifson JD, De Rose R, Kent SJ. Inactivated SIV-pulsed autologous fresh blood cells as an immunotherapy strategy. Journal of Virology, 2009; 83: 1501-1510.
De Rose R, Zelikin A, Johnston APR, Sexton A, Chong SF, Cortez C, Mulholland W, Caruso F, Kent SJ. Binding, Internalisation and Antigen Presentation of Vaccine-Loaded Nanoengineered Capsules in Blood. Advanced Materials, 2008; 20: 4698-4703.
Smith MZ, Asher TE, Venturi V, Davenport MP, Douek DC, Price DA, Kent SJ. Limited maintenance of vaccine-induced SIV-specific CD8 T cell receptor clonotypes after virus challenge. J Virol, 2008; 82: 7357-7368.
De Rose R, Fernandez CS, Smith MZ, Batten CJ, Alcantara S, Peut V, Rollman E, Loh L, Mason RD, Wilson K, Law MG, Handley AJ, Kent SJ. Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood. PloS Pathogens, 2008; 4(5): e1000055. doi:10.1371/journal.ppat.1000055.
Stratov I, Chung A, Kent SJ. Robust NK-cell mediated HIV-specific antibody-dependent responses in HIV-infected subjects. J Virol, 2008; 82: 5450-5459.
Loh L, Petravic J, Batten CJ, Davenport MP, Kent SJ. Vaccination and timing influence SIV immune escape viral dynamics in vivo. PloS Pathogens, 2008; 4(1): e12 doi:10.1371/journal.ppat.0040012.
Rollman E, Smith MZ, Brooks A, Purcell DFJ, Zuber B, Ramshaw IA, Kent SJ. Killing kinetics of SIV-specific CD8+ T cells: implications for HIV vaccine strategies. Journal of Immunology, 2007;179:4571-4579.