Dr Robert Center
Robert Center BSc (Hons) PhD
|Academic Degrees||Contact Details|
|Year: BSc Hons, University
Year: PhD, University
|Tel: +61 3 8344 9779
Fax: + 61 9347 1540
Room 2.01A, Department of Microbiology & Immunology
|Year to Present, Senior Research Officer|
A current major focus of my work is directed toward HIV vaccine development. Infection with HIV is initiated when the HIV envelope protein mediates binding of the virus to a target cell. Our aim is to harness the power of protective antibodies that can bind to the envelope protein and block target-cell recognition and subsequent infection. Vaccines often generate better immune responses when two different vaccine modalities are used in so-called prime/boost strategies. We have used DNA vectors expressing envelope protein for the first vaccination (prime). One aspect of my work involves improving the design of our DNA vectors to increase the efficiency with which they prime the immune system. Purified protein is used to boost the immune response boost. The functional HIV envelope protein is composed three gp120 subunits and three gp41 subunits as shown in Figure 1. This structure, known as a trimer, is an important element in the way the human immune system recognizes the envelope protein. I have developed the tools and techniques to purify envelope protein trimers for testing as vaccines. A hurdle to an HIV vaccine is the variability of many parts of the envelope protein between different viral strains. By manipulating the envelope protein to expose the less variable regions we hope to generate antibodies capable of blocking infection caused by diverse HIV isolates. These strategies will be utilized for preventative vaccine development and for producing antibodies that may be used in a topical microbicide. I am also involved in basic research studies focusing on the structure and function of the envelope protein.
- Johansson SE, Rollman E, Chung AW, Center RJ, Hejdeman B, Stratov I, Hinkula J, Wahren B, Kärre K, Kent SJ, Berg L. NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and controller patients. Viral Immunology 2011; 24: 359-68.
- Chung AW, Navis M, Isitman G, Centre R, Finlayson R, Bloch M, Gelgor L, Kelleher A, Kent SJ, Stratov I. Activation of NK cells by ADCC responses during early HIV infection. Viral Immunology 2011; 24: 171-5.
- Kramski M, Gaeguta AJ, Lichtfuss GF, Rajasuriar R, Crowe SM, French M, Lewin SR, Center RJ, Purcell DF. A novel sensitive real-time PCR for the quantification of bacterial 16S rDNA in the plasma of HIV infected patients as marker for microbial translocation. Journal of Clinical Microbiology in press (2011).
- Kirkegaard T, Wheatley A, Melchjorsen J, Bahrami S, Pedersen FS, Center RJ, Purcell DF, Ostergaard L, Duch M, Tolstrup M. Induction of humoral and cellular immune responses against the HIV-1 envelope protein using gamma-retroviral virus-like particles. Virology Journal 2011; 8: 381
- Chung AW, Isitman G, Navis M, Kramski M, Center RJ, Kent SJ, Stratov I. Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure. Proc Natl Acad Sci USA 2011; 108: 7505-10,
- Wheatley AK, Kramski M, Alexander MR, Toe JG, Center RJ, Purcell DF. Co-Expression of miRNA Targeting the Expression of PERK, but Not PKR, Enhances Cellular Immunity from an HIV-1 Env DNA Vaccine. PLoS One 2011; 6: e18225
- Azimi I, Matthias LJ, Center RJ, Wong JW, Hogg PJ. Disulfide bond that constrains the HIV-1 gp120 V3 domain is cleaved by thioredoxin. J Biol Chem 2010; 285: 40072-80.
- Alexander MR, Wheatley AK, Center RJ, Purcell DF. Efficient transcription through an intron requires the binding of an Sm-type U1 snRNP with intact stem loop II to the splice donor. Nucleic Acids Research 2010; 38: 3041-53.
- Center RJ, Wheatley AK, Campbell SM, Gaeguta AJ, Peut V, Alcantara S, Siebentritt C, Kent SJ, Purcell DF. Induction of HIV-1 subtype B and AE-specific neutralizing antibodies in mice and macaques with DNA prime and recombinant gp140 protein boost regimens. Vaccine 2009; 27: 6605-12.
- Peut V, Campbell S, Gaeguta A, Center RJ, Wilson K, Alcantara S, Fernandez CS, Purcell DF, Kent SJ. Balancing reversion of CTL and neutralizing antibody escape mutations within HIV-1 Env upon transmission. Journal of Virology 2009; 83: 8986-92.
- Loh L, Reece JC, Fernandez CS, Alcantara S, Center R, Howard J, Purcell DF, 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: e1000378.
- 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: 1202-10.
- Miller A, Center RJ, Stambas J, Deliyannis G, Doherty PC, Howard JL, Turner SJ, Purcell DF. Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination. Vaccine 2008; 26: 5641-8.