Dr Laura Rivino

WELCOME TO THE ANTI-VIRAL T CELL IMMUNITY LABORATORY

Our group studies the biology and role of T cells during flavivirus infection and vaccination, with a particular interest in dengue virus infection.

Vision

Virus-specific T cells constitute an essential line of defence during viral infection and both an impaired or exacerbated T cell response are detrimental to the host. We are interested in understanding how T cells contribute to protective immunity and/or immunopathology during viral infection, particularly in the context of dengue infection. Understanding these mechanisms is critical for the development of effective vaccines and host-directed therapeutics.   

Dengue virus causes the most prevalent mosquito-borne viral infection afflicting humans, with a recent estimate of 390 million infections per year. No specific therapeutics and only a partially protective vaccine are available for dengue. Dengue infection can cause an uncomplicated febrile illness or more severe syndromes which are characterized by increased vascular permeability and plasma leakage and can potentially progress to dengue shock syndrome. The host immune response is believed to drive severe disease, but the contribution of T cells in these processes remains unc­­­lear.

Mission and impact

We aim to define the T cell response during dengue infection and how it relates to clinical outcomes to inform the development of effective vaccines and host-directed therapies for dengue and related flaviviruses.

Approach

Our group performs translational immunological research on samples from patients, vaccine recipients and healthy donors.  We address the phenotype, functional capacity and gene expression of T cells by utilizing a range of methodologies including multi-dimensional flow cytometry, CyTOF, ELISPOT, RNAseq and immunohistochemistry. Our work is performed in collaboration with Duke-NUS Medical School, Tan Tock Seng Hospital (Singapore), the Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City (Vietnam) and Cambridge University.

Currently our lab is working on:

  1. Phenotypic and transcriptional T cell signatures associated with severe dengue. Preliminary data suggests that T cell signatures associated with CD8+ T cell exhaustion and CD4+ T cell co-stimulation correlate with the development of severe dengue (McKinney et al Nature 2015). We aim to validate the association between T cell responses and immunopathology  and define the mechanisms underlying these processes.
  2. Characteristics of circulating and tissue-resident T cells. We have previously shown that a large proportion of dengue-specific T cells reside within the skin tissue during acute dengue infection (Rivino et al Sc Transl Med 2015). We aim to define the nature and role of dengue-specific T cells in the skin and the relationship they have with their blood counterparts. 
  3. Impact of cross-reactive T cell recognition on anti-viral T cell function. We aim to define the impact of cross-reactive T cell recognition of the different dengue serotypes or of related flaviviruses on the anti-viral function of CD8+ T cells to understand how this may affect disease outcomes during secondary dengue or sequential flavivirus infections.
  4. Yellow fever virus (YFV) vaccination as a model for flavivirus immunity. We aim to define how different components of the innate (NK cells) and adaptive (T and B cells) immune response are interconnected with each other and contribute to the efficacy of YFV, one of the most successful vaccines in history.

Funding

Our work has received the generous support of NMRC and Duke-NUS Medical School in Singapore.

Qualifications and history

  • 2019-present: Senior Lecturer, University of Bristol, UK.
  • 2016-2019: Assistant Professor, Duke-NUS Medical School, Singapore.
  • 2014-2016: Head of Flow Cytometry core facility and Senior post-doctoral Research Fellow, Duke-NUS Medical School, Singapore.
  • 2009-2013: Post-doctoral Research Fellow, National University of Singapore, Singapore.
  • 2007: Research Scientist, Charite’ Medical University of Berlin and German Arthritis Research Centre (DRFZ), Berlin, Germany.
  • 2007: PhD in Immunology, Institute for Research in Biomedicine, Bellinzona, Switzerland.

Selected publications

Find further publications in Explore Bristol Research

*Indicates equal contribution

  1. Zimmer CL, Cornillet M, Solà-Riera C, Cheung KW, Ivarsson MA, Lim MQ, Marquardt N, Leo YS, Lye DC, Klingström J, MacAry PA, Ljunggren HG, *Rivino L, *Björkström NK. NK cells are activated and primed for skin-homing during acute dengue virus infection in humans. Nat Commun. 2019 Aug 29;10(1):3897.
  2. Lim MQ, Kumaran EAP, Tan HC, LyeDC, Leo YS, Ooi EE, MacAry PA, Bertoletti A and Rivino L. Cross-reactivity and Anti-viral function of Dengue Capsid and NS3-Specific Memory T cells Toward Zika Virus. Front Immunol 2018 Oct 1;9:2225.
  3. *Rivino L, *Le Bert N, Gill U,Cheng Y, Kunasegaran K, Tan D, Hansi NK, Foster GR, Su TH, Tseng TC, Lim SG, Kao JH, Newell E, Kennedy P & Bertoletti A. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J Clin Invest 2018 Jan 8. pii: 92812.
  4. Rivino L, Kumaran EK, Linn TT, Too CT, Gan VCH, Hanson BJ, Annelies Wilder-Smith, Gascoigne N, Lye DC, Leo YS, Akbar AK, Kemeny DM and MacAry PA. Virus-specific T lymphocytes home to the skin during natural dengue infection. Sci Transl Med 2015 Mar 11;7(278):278ra35.
  5. Rivino L, Kumaran EA, Jovanovic V, Nadua K, Teo EW, Pang SW, Teo GH, Gan VC, Lye DC, Leo YS, Hanson BJ, Smith KG, Bertoletti A, Kemeny DM, Macary PA. Differential Targeting of Viral Components by CD4+ versus CD8+ T Lymphocytes in Dengue Virus Infection. J Virol 2013 Mar; 87(5):2693-706.

In the media

Read the press release by the Singapore Straits times on our study identifying the skin as a site for the immunosurveillance of dengue virus.

Dr Laura Rivino
Dr Laura Rivino
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