Wolbachia to stop dengue transmission in Vietnam and Indonesia

Project Details

The Eliminate Dengue consortia (www.eliminatedengue.com/program is establishing Wolbachia in Aedes aegypti mosquito populations in South East Asia and Latin America.  Wolbachia durably and stably reduces the ability of mosquitoes to transmit dengue and thus offers a standalone intervention for dengue control. Cameron’s group provides expert leadership in understanding the virus blocking capacity of Wolbachia and the conduct of field trials that will deliver gold-standard evidence of its public health benefits. This work is part supported by NHMRC program funding.

Correlates of immunity

Cameron’s group has developed a novel assay that enables measurement of the potency of monoclonal and polyclonal antibodies to neutralise the infectivity of dengue viruses present in freshly collected viremic blood from patients. With NHMRC support, they are deploying this assay to identify the most potent virus-neutralising human mAbs and their cognate epitopes. These studies will inform vaccine design and correlative assays of immunity.

Virus diversity versus efficacy in phase III vaccine trials (collaboration with Sanofi Pasteur)

In collaboration with Sanofi Pasteur, Cameron’s group is using genomics to assess virus population diversity to understand the performance of the Sanofi Pasteur dengue vaccine candidate, CYD-TDV. They have established a whole genome sequencing platform and analysis pipeline to identify potential antigenic drift in the virus population during and after vaccine trials.

Homotypic dengue human challenge studies

With NHMRC support, Cameron’s group is developing a model of experimental dengue virus challenge of adult volunteers with previously documented histories of dengue virus infection.  The rationale is to enable virological and immunological insights into the characteristics of clinical immunity.

Researchers

Melbourne

Kirsty McPherson, Research Officer
Gayathri Manokaran, Research Officer
Julio Carrera, PhD Student
Sujatmoko Sujatmoko, Masters Student
Diane Sainato, Administrative Assistant

Vietnam

Lauren Carrington, Research Officer
Kien Duong Thi Hue, Senior Research Assistant
Trung Vu Tuan, PhD Student
Thuy Nguyen Thi Van, Research Assistant
Nguyet Nguyen Minh, Postdoc Clinician
Vi Tran Thuy, Research Assistant
Huy Huynh Le Anh, Research Assistant
Long Thi, Research Assistant
Dui Le Thi, Research Assistant
Nhu Vu Tuyet, Research Assistant
Giang Nguyen Thi, Research Assistant
Van Huynh Thi Thuy, Research Assistant
Trang Huynh Thi Xuan, Research Assistant

Collaborators

S. Baker,
E Harris,
G Screaton,
EE Ooi,
P Young,
ML Hibberd,
NM Ferguson,
SL O'Neill,
A Hoffmann

Funding

NHMRC

Wellcome Trust

Industry

Bill and Melinda Gates Foundation

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

  1. Lam PK, Ngoc TV, Thu Thuy TT, Hong Van NT, Nhu Thuy TT, Hoai Tam DT, Dung NM, Hanh Tien NT, Thanh Kieu NT, Simmons C, et al. The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue. PLoS Negl Trop Dis 2017 April; 11(4):e0005498. 
  2. Nguyen MT, Ho TN, Nguyen VVC, Nguyen TH, Ha MT, Ta VT, Nguyen LDH, Phan L, Han KQ, Duong THK, et al. An Evidence-Based Algorithm for Early Prognosis of Severe Dengue in the Outpatient Setting. Clinical Infectious Diseases 2017 Mar; 64(5): 656-663. 
  3. Cuong HQ, Henrik S, Isabel R-B, In-Kyu Y, Nguyen VVC, Nguyen TH, Ha MT, Phan TL, Willis B, Nisalak A, et al. Synchrony of Dengue Incidence in Ho Chi Minh City and Bangkok. PLOS Neglected Tropical Diseases 2016 Dec; 10(12): 18.
  4. Recker M, Vannice K, Hombach J, Jit M, Simmons CP. Assessing dengue vaccination impact: Model challenges and future directions. Vaccine 2016 Aug; 34(38): 4461-4465.
  5. Clapham HE, Than HQ, Duong THK, Dorigatti I, Simmons CP, Ferguson NM. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance. PLOS Computational Biology 2016 May; 12(5): 15.
  6. Ferguson NM, et al, Simmons CP. Modeling the impact on virus transmission of <em>Wolbachia</em>-mediated blocking of dengue virus infection of <em>Aedes aegypti</em>. Sci Transl Med 2015 Mar; 18;7(279):279ra37.
  7. James Whitehorn et al, Cameron P. Simmons, B. Wills. Lovastatin for the treatment of adult patients with dengue: a randomised, double-blind, placebo-controlled trial.  Clin Infect Dis 2016 Feb; 62(4): 468-76.
  8. Simmons CP. A Candidate Dengue Vaccine Walks a Tightrope. N Engl J Med 2015 Jul 27.
  9. Simmons CP, Farrar, J, NVV Chau, B. Wills. Current Concepts: Dengue. N Engl J Med 2012 Apr; 366(15): 1423-32.
  10. Nguyet MN, et al. Simmons CP. Host and viral features of human dengue cases shape the population of infected and infectious <em>Aedes aegypti</em> mosquitoes. Proc Natl Acad Sci USA 2013 May; 110(22): 9072-7.
  11. Chiea Chuen Khor, et al and Cameron P. Simmons. MICB and PLCE1 are associated with Dengue shock syndrome. Nature Genetics 2011 Oct; 43(11): 1139-41.
  12. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI.  The global distribution and burden of dengue. Nature 2013 Apr; 496(7446): 504-7.
  13. Nguyen Minh Nguyet, et al, Cameron P. Simmons. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis 2013 May; 207(9): 1442-50.
  14. Raghwani J, et al, Simmons CP. Endemic dengue associated with the co-circulation of multiple viral lineages and localized density-dependent transmission. PLoS Pathog 2011 Jun; 7(6): e1002064.
  15. Dejnirattisai W, Wongwiwat W, Supasa S, Zhang X, Dai X, Rouvinsky A, Jumnainsong A, Edwards C, Quyen NT, Duangchinda T, Grimes JM, Tsai WY, Lai CY, Wang WK, Malasit P, Farrar J, Simmons CP, Zhou ZH, Rey FA, Mongkolsapaya J, Screaton GR. A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus. Nat Immunol 2015 Feb; 16(2): 170-7.

Research Group

Simmons laboratory: Dengue; pathogenesis, epidemiology, therapeutics, entomology



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease, Therapeutics & Translation



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Microbiology and Immunology

Unit / Centre

Simmons laboratory: Dengue; pathogenesis, epidemiology, therapeutics, entomology