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Viral Entry and Vaccines Group

Co-Heads: Professor Heidi Drummer and Dr Andy Poumbourios 

HIV infects more than 37 million people world-wide and results in almost two million deaths each year. HCV is estimated to chronically infect three percent of the world’s population causing 350 million deaths each year. In the United States, deaths due to HCV now outnumber those caused by HIV, and HCV is now the major indicator of liver transplants in the developed world. 

No vaccines are available for HCV or HIV.

Whilst the use of highly-active antiretroviral therapy has seen a dramatic increase in the life expectancy of HIV infected people, the virus still cannot be eliminated.

Over time, viruses can become resistant to the antiviral agents and patients may succumb to AIDS. In the case of HCV, direct acting antiviral therapies are now available in the market place and whilst there has been a dramatic improvement in the number of people achieving a sustained virological response, the high cost of treatment will restrict their availability. As such, it is unlikely that sufficient people will receive treatment to reduce the burden of disease.

Like other viruses, HIV and HCV attach to the surface of target cells via specific interactions with cellular receptors. Both HIV and HCV must then undergo the process of membrane fusion before they can enter the cell and begin their replication cycle.

The Viral Entry and Vaccines Group aims to gain a better understanding of how viruses attach to and enter target cells. The surface of HIV and HCV particles are decorated with the viral glycoproteins that mediate specific interactions with host cell receptors. Binding of the viral glycoproteins to these receptors induces conformational changes that prime the glycoproteins to mediate viral fusion.

During viral fusion, the lipid bilayer of the virus and host cell merge and begin to form a small pore. Expansion of this pore then allows the contents of the virus to be delivered and initiates viral replication. The viral glycoproteins are major targets of the antibody response during infection. These antibodies can block the ability of the virus to interact with the cellular receptors, or they can prevent the conformational changes required to mediate viral fusion and are termed neutralising antibodies.

In the case of HIV and HCV, the viruses have evolved mechanisms to evade this neutralising antibody response and have hampered efforts to produce vaccines. In addition, both HIV and HCV are highly variable pathogens and so it is necessary to produce a vaccine that has the ability to prevent infection of multiple clades/genotypes that circulate globally.

The Viral Entry and Vaccines Group aims to understand how virus entry occurs and develop novel vaccine candidates against HIV and HCV.

HCV studies

  • Development of a prophylactic vaccine for HCV Understanding the role of the variable regions in modulating virus entry and neutralisation by antibody
  • Expression of recombinant HCV glycoproteins for structure determination Virus and antibody evolution.

HIV studies

  • The role of conformational signalling between gp120 and gp41 in HIV entry
  • The role of the polar segment and membrane proximal external region in HIV entry Identification of functional linkages between gp120 and gp41
  • Development of novel HIV vaccine candidates.

Our group conducts studies into three of the world’s most destructive human pathogens – SARS-CoV-2 (COVID-19), Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV).

Hear more from Viral Entry and Vaccines Group Co-Head, Professor Heidi Drummer, in Episode 2 of our How Science Matters podcast. 

Listen here.

Highlights from our working group includes:

  • Drummer HE. 2014. Challenges to the development of vaccines to hepatitis C virus that elicit neutralizing antibodies. Front Microbiol 5:329.
  • Sacks-Davis R, Aitken CK, Higgs P, Spelman T, Pedrana AE, Bowden S, Bharadwaj M, Nivarthi UK, Suppiah V, George J, Grebely J, Drummer HE, Hellard M. 2013. High rates of hepatitis C virus reinfection and spontaneous clearance of reinfection in people who inject drugs: a prospective cohort study. PLoS One 8:e80216.
  • Khasawneh AI, Laumaea A, Harrison DN, Bellamy-McIntyre AK, Drummer HE, Poumbourios P. 2013. Forced virus evolution reveals functional crosstalk between the disulfide bonded region and membrane proximal ectodomain region of HIV-1 gp41. Retrovirology 10:44.
  • Drummer HE, Hill MK, Maerz AL, Wood S, Ramsland PA, Mak J, Poumbourios P. 2013. Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1) N-glycans linked to neutralization sensitivity. PLoS Pathog 9:e1003218.
  • McCaffrey K, Boo I, Tewierek K, Edmunds ML, Poumbourios P, Drummer HE. 2012. The role of conserved cysteine residues in Hepatitis C virus glycoprotein E2 folding and function. J Virol 86:3961-3974.
  • Boo I, Tewierek K, Douam F, Lavillette D, Poumbourios P, Drummer HE. 2012. Distinct roles in folding, CD81 receptor binding and viral entry for conserved histidines of HCV glycoprotein E1 and E2. Biochem J 443:85-94.
  • McCaffrey K, Gouklani H, Boo I, Poumbourios P, Drummer HE. 2011. The variable regions of hepatitis C virus glycoprotein E2 have an essential structural role in glycoprotein assembly and virion infectivity. J Gen Virol 92:112-121.
  • Lay CS, Ludlow LE, Stapleton D, Bellamy-McIntyre AK, Ramsland PA, Drummer HE, Poumbourios P. 2011. Role for the terminal clasp of HIV-1 gp41 glycoprotein in the initiation of membrane fusion. J Biol Chem 286:41331-41343.
  • Fraser J, Boo I, Poumbourios P, Drummer HE. 2011. Hepatitis C virus (HCV) envelope glycoproteins e1 and e2 contain reduced cysteine residues essential for virus entry. J Biol Chem 286:31984-31992.
  • Drummer HE, McKeating JA. 2011. HCV receptors and entry inhibitors. In He S-LTaY (ed), Hepatitis C: Antiviral Drug Discovery and Development. Caister Academic Press.
  • Bellamy-McIntyre AK, Bar S, Ludlow L, Drummer HE, Poumbourios P. 2010. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function. Biochem Biophys Res Commun 394:904-908.
  • Aitken CK, Lewis J, Tracy SL, Spelman T, Bowden DS, Bharadwaj M, Drummer H, Hellard M. 2008. High incidence of hepatitis C virus reinfection in a cohort of injecting drug users. Hepatology 48:1746-1752. 
  • Wilson KA, Maerz AL, Bar S, Drummer HE, Poumbourios P. 2007. An N-terminal glycine-rich sequence contributes to retrovirus trimer of hairpins stability. Biochem Biophys Res Commun.
  • Poumbourios P, Drummer HE. 2007. Recent advances in our understanding of receptor binding, viral fusion and cell entry of hepatitis C virus: new targets for the design of antiviral agents. Antivir Chem Chemother 18:169-189.
  • McCaffrey K, Boo I, Poumbourios P, Drummer HE. 2007. Expression and characterization of a minimal hepatitis C virus glycoprotein E2 core domain that retains CD81 binding. J Virol 81:9584-9590.
  • Bellamy-McIntyre AK, Lay CS, Baar S, Maerz AL, Talbo GH, Drummer HE, Poumbourios P. 2007. Functional links between the fusion peptide-proximal polar segment and membrane-proximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. J Biol Chem 282:23104-23116.

Professor Heidi Drummer

Professor Heidi Drummer is Program Director for Disease Elimination and co-Head of the Viral Entry and Vaccines research group at Burnet Institute. In 2021, she was appointed as Scientific Director of the Burnet Diagnostics Initiative, a new Burnet Initiative to progress diagnostics through to human health solutions.

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Projects

ACE2 inhibitors for treatment of COVID-19
PROJECT ACE2 inhibitors for treatment of COVID-19
COVID-19 antigens for PoC test development
PROJECT COVID-19 antigens for PoC test development
Hepatitis C: Community Testing and Treatment (CT2)
PROJECT Hepatitis C: Community Testing and Treatment (CT2)
HepSeeVax: Proof-of-concept study of an HCV vaccine candidate
PROJECT HepSeeVax: Proof-of-concept study of an HCV vaccine candidate
Neutralising antibody assays for COVID-19
PROJECT Neutralising antibody assays for COVID-19
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COVID-19 antigens for PoC test development
PROJECT COVID-19 antigens for PoC test development
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PROPHECY: Profiling immune Responses in Paediatric and High-risk populations to SARS-CoV-2
PROJECT PROPHECY: Profiling immune Responses in Paediatric and High-risk populations to SARS-CoV-2
Understanding how HCV evades the immune system
PROJECT Understanding how HCV evades the immune system
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Understanding immune responses to Mpox infection and vaccination
PROJECT Understanding immune responses to Mpox infection and vaccination
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Understanding the correlates of protection for hepaciviruses
PROJECT Understanding the correlates of protection for hepaciviruses
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Identifying risk factors and biomarkers of post-acute sequelae COVID-19 (PASC, Long COVID)
PROJECT Identifying risk factors and biomarkers of post-acute sequelae COVID-19 (PASC, Long COVID)