Dr Mohammed Alsharifi

• Biography/ Background

  Dr Alsharifi studied Biomedical Science at Monash University. After graduating with First Class Honours, he moved to the Australian National University to take up a PhD scholarship at The John Curtin School of Medical Research. During his PhD, he investigated with Prof Arno Müllbacher, Prof Robert Blanden, and Dr Mario Lobigs the immunobiology of an alphavirus infection. During his early years in research he discovered a period of exhaustion in type-I interferon response following an acute viral infection, which may explain the clinically known observation that virus-infected patients are at increased risk to a more sever secondary viral and/or bacterial infection. Following the completion of his PhD studies, he investigated with Prof Müllbacher the possibility of using gamma-irradiated influenza virus as a universal flu vaccine. In 2008, he was awarded the Hanson Fellowship to continue his research into the universal Flu vaccine and also to investigate the possibility of producing other vaccines using similar technique to that used for influenza. His flu vaccine research has been featured in the Catalyst program on ABC (http://www.abc.net.au/catalyst/stories/2613604.htm), and in many newspaper articles such as (http://www.news.com.au/adelaidenow/story/0,,25625291-5018662,00.html) and  (http://www.news.com.au/adelaidenow/story/0,22606,25406694-5006301,00.html).

• Research Interests

  Opportunities for post doctoral fellows and postgraduate students

   

  Concepts Related to the Development of Gamma-Irradiated Vaccines:

  Gamma irradiation has become a “gold standard” for inactivating highly dangerous pathogens such as the Ebola virus. However, despite our advance knowledge, more investigations are required for a much better understanding of the conditions and parameters required to achieve sterility of infectious materials in accordance with the international benchmark, the “Sterility Assurance Level”. This project is expected to systematically investigate the underlying parameters influencing the sterility of γ-irradiated preparations. It will allow us to quantify any structural damage induced by γ-irradiation in viruses and bacteria and also to classify viruses and bacteria based on their suitability as γ-irradiated vaccine candidates.

   

  Cross-Protective Influenza Vaccine:

  Protection against re-infection with homotypic influenza virus is mediated primarily by neutralizing antibodies but recovery from newly arisen influenza virus infections requires cytotoxic CD8+ T (Tc) cells. While neutralizing antibodies target mainly the viral surface glycoproteins (HA and NA), which are subject to frequent antigenic variation, influenza-immune Tc cells target the more conserved proteins, such as the viral nucleoprotein (NP) and matrix protein. Accordingly, any universal influenza vaccine should have the capability of inducing cross-protective Tc cell responses. We have developed cross-protective influenza A virus vaccine and we aim to investigate CTL responses in terms of activation, recruitments into the lung and long term tissue persistence.

    

  Exhaustion of IFN-I Response and the Susceptibility to Secondary Infections:

  We have previously reported that type I interferon (IFN-I) response mediates systemic, partial lymphocyte activation which is evident by elevated expression of CD69 and CD86. Interestingly, we have found a period of exhausted IFN-I responses as a result of primary viral infections, which was associated with enhanced susceptibility to a secondary infection with an unrelated virus. Our aim is to investigate the underlying factors responsible for the deficiency in IFN-I responses following acute viral infections, and to address some therapeutic approaches to alleviate the period of the enhanced susceptibility.

• Publications

  23. Babb R, Chen A, Ogunniyi AD, Hirst TR, Kara EE, McColl SR, Alsharifi M, Paton JC. Enhanced protective responses to a serotype independent pneumococcal vaccine when combined with an inactivated influenza vaccine. Clin Sci (Lond). 2016 Nov 24. pii: CS20160475. [Epub ahead of print]

   

  22. Stevens NE, Hatjopolous A, Fraser CK, Alsharifi M, Diener KR, Hayball JD. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection. Sci Rep. 2016 Jul 6;6:29154. doi: 10.1038/srep29154. PMID: 27380890 Free PMC Article

   

  21. Babb R, Chen A, Hirst TR, Kara EE, McColl SR, Ogunniyi AD, Paton JC, Alsharifi M. Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses. Clin Sci (Lond). 2016 May;130(9):697-710. doi: 10.1042/CS20150699. PMID: 26831937

   

  20. Chan J, Babb R, David SC, McColl SR, Alsharifi M. Vaccine-Induced Antibody Responses Prevent the Induction of Interferon Type I Responses Upon a Homotypic Live Virus Challenge. Scand J Immunol. 2016 Mar;83(3):165-73. doi: 10.1111/sji.12410. PMID: 26715418

   

  19. Babb R, Chan J, Khairat JE, Furuya Y, Alsharifi M. Gamma-Irradiated Influenza A Virus Provides Adjuvant Activity to a Co-Administered Poorly Immunogenic SFV Vaccine in Mice. Front Immunol. 2014 Jun 10;5:267. doi: 10.3389/fimmu.2014.00267. PMID: 24959166 Free PMC Article

   

  18. Ebrahimi M, Aghagolzadeh P, Shamabadi N, Tahmasebi A, Alsharifi M, Adelson DL, Hemmatzadeh F, Ebrahimie E. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein. PLoS One. 2014 May 8;9(5):e96984. doi: 10.1371/journal.pone.0096984. Erratum in: PLoS One. 2014;9(6):e99921. PMID: 24809455 Free PMC Article

   

  17. Stevens NE, Fraser CK, Alsharifi M, Brown MP, Diener KR, Hayball JD. An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT™ is functionally superior to Freund's adjuvant. PLoS One. 2013 Jul 23;8(7):e68895. doi: 10.1371/journal.pone.0068895. PMID: 23894371 Free PMC Article

   

  16. Alsharifi M, Koskinen A, Wijesundara DK, Bettadapura J, Müllbacher A. MHC class II-alpha chain knockout mice support increased viral replication that is independent of their lack of MHC class II cell surface expression and associated immune function deficiencies. PLoS One. 2013 Jun 28;8(6):e68458. doi: 10.1371/journal.pone.0068458. PMID: 23840854 Free PMC Article

   

  15. Furuya Y, Chan J, Wan EC, Koskinen A, Diener KR, Hayball JD, Regner M, Müllbacher A, Alsharifi M. Gamma-irradiated influenza virus uniquely induces IFN-I mediated lymphocyte activation independent of the TLR7/MyD88 pathway. PLoS One. 2011;6(10):e25765. doi: 10.1371/journal.pone.0025765. PMID: 21998693 Free PMC Article

   

  14. Wijesundara DK, Kumar S, Alsharifi M, Müllbacher A, Regner M. Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I-mediated partial lymphocyte activation. Int Immunol. 2010 Sep;22(9):757-67. doi: 10.1093/intimm/dxq064. PMID: 20682547 Free Article

   

  13. Furuya Y, Chan J, Regner M, Lobigs M, Koskinen A, Kok T, Manavis J, Li P, Müllbacher A, Alsharifi M. Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses. J Virol. 2010 May;84(9):4212-21. doi: 10.1128/JVI.02508-09. PMID: 20164231 Free PMC Article

   

  12. Furuya Y, Regner M, Lobigs M, Koskinen A, Müllbacher A, Alsharifi M. Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations. J Gen Virol. 2010 Jun;91(Pt 6):1450-60. doi: 10.1099/vir.0.018168-0. PMID: 20147516

   

  11. Alsharifi M, Müllbacher A. The gamma-irradiated influenza vaccine and the prospect of producing safe vaccines in general. Immunol Cell Biol. 2010 Feb;88(2):103-4. doi: 10.1038/icb.2009.81. No abstract available. PMID: 19859081

   

  10. Alsharifi M, Furuya Y, Bowden TR, Lobigs M, Koskinen A, Regner M, Trinidad L, Boyle DB, Müllbacher A. Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections. PLoS One. 2009;4(4):e5336. doi: 10.1371/journal.pone.0005336. PMID: 19401775 Free PMC Article

   

  9. Lobigs M, Larena M, Alsharifi M, Lee E, Pavy M. Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective values against Murray Valley encephalitis virus. J Virol. 2009 Mar;83(6):2436-45. doi: 10.1128/JVI.02273-08. PMID: 19109382 Free PMC Article

   

  8. Alsharifi M, Lobigs M, Bettadapura J, Koskinen A, Müllbacher A. Restricted Semliki Forest virus replication in perforin and Fas-ligand double-deficient mice. J Gen Virol. 2008 Aug;89(Pt 8):1942-4. doi: 10.1099/vir.0.83626-0. PMID: 18632965

   

  7. Alsharifi M, Müllbacher A, Regner M. Interferon type I responses in primary and secondary infections. Immunol Cell Biol. 2008 Mar-Apr;86(3):239-45. doi: 10.1038/sj.icb.7100159. Review. PMID: 18180794

   

  6. Budd A, Alleva L, Alsharifi M, Koskinen A, Smythe V, Müllbacher A, Wood J, Clark I. Increased survival after gemfibrozil treatment of severe mouse influenza. Antimicrob Agents Chemother. 2007 Aug;51(8):2965-8. PMID: 17562808 Free PMC Article

   

  5. Alsharifi M, Regner M, Blanden R, Lobigs M, Lee E, Koskinen A, Müllbacher A. Exhaustion of type I interferon response following an acute viral infection. J Immunol. 2006 Sep 1;177(5):3235-41. PMID: 16920963 Free Article

   

  4. Müllbacher A, Lobigs M, Alsharifi M, Regner M. Cytotoxic T-cell immunity as a target for influenza vaccines. Lancet Infect Dis. 2006 May;6(5):255-6. PMID: 16631540

   

  3. Alsharifi M, Lobigs M, Simon MM, Kersten A, Müller K, Koskinen A, Lee E, Müllbacher A. NK cell-mediated immunopathology during an acute viral infection of the CNS. Eur J Immunol. 2006 Apr;36(4):887-96. PMID: 16541469 Free Article

   

  2. Rosen DB, Bettadapura J, Alsharifi M, Mathew PA, Warren HS, Lanier LL. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol. 2005 Dec 15;175(12):7796-9. PMID: 16339513 Free Article

   

  1. Alsharifi M, Lobigs M, Regner M, Lee E, Koskinen A, Müllbacher A. Type I interferons trigger systemic, partial lymphocyte activation in response to viral infection. J Immunol. 2005 Oct 1;175(7):4635-40. PMID: 16177109 Free Article

Entry last updated: Thursday, 12 Jan 2023

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