5 Monivong Boulevard, P.O Box. 983, Phnom Penh, Cambodia [email protected]
    • 16 MAR 16

    Seminar on the Complexity for the development of dengue vaccines, by Dr. Vincent DEUBEL

    The Committee of Scientific Animation of Institut Pasteur du Cambodge will organise a seminar on the “Complexity for the development of dengue vaccines”, by Dr. Vincent DEUBEL.

    The seminar will take place on Thursday 24th March 2016, at 3:00pm, in IPC’s meeting room, first floor.

    Free admission. Any question, please contact us by email: [email protected]org

    SUMMARY

    Dengue is caused by one of four viral serotypes in the flavivirus genus transmitted by Aedes mosquitoes. The four dengue viruses (DENV) are endemic to more than 100 tropical countries worldwide and 50% of the world’s population is at risk of this disease, with 100 million infections annually, 500,000 hospitalization and over 20,000 dengue related deaths, mainly in children.

    The development of a vaccine against dengue has been challenged by several factors including (1) heterogeneity of DENV; (2) risk of antibody-dependent enhancement and original antigenic sin in incomplete immunity; (3) no defined positive in vitro markers of attenuation; (4) no appropriate animal models for preclinical trials; (5) absence of accurate immune correlates of protection or risk.

    The recent development of structural analysis of DENV particles1 and of envelope proteins2 with analysis of their interaction with human neutralizing monoclonal antibodies3 offers new insights in complex tertiary structures needed to induce the right type of neutralizing antibody response. However, antigenic analysis of a panel of DENV types showed that they do not fall into order as distinct serotypes4.

    Moreover, important lessons learned from efficacy studies obtained on the recent phase IIb trial of a tetravalent dengue vaccine conducted by Sanofi Pasteur in Thailand5 were the absence of link between the levels of neutralizing antibodies and protection, and the importance of varying serotype-specific efficacy. Two following phase III trials carried out in Asia6 and South America7 reached acceptable safety and efficacy against dengue disease and against the number of DHF cases and hospitalization in children aged 9 years.

    Other life attenuated dengue vaccine candidates are under phase II and phase IIb trials and more information is needed from vaccine producers and researchers to tackle complexity of vaccine and bring innovation for a safe and efficient vaccine against all four dengue serotypes.

     

    1. X Zhang et al., PNAS, 2013 ;

    2. G Fibriansah et al., Science, 2015 ;

    3. G Fibriansah et al., Nature Com., 2015 ; W Dejnirattisai et al., Nature Immunol. 2015 ;

    4. LC Katzelwick et al., Science, 2015 ;

    5. A Sabchareaon et al., Lancet, 2012 ;

    6. MR Capeding et al., Lancet, 2014 ;

    7. L Villar et al., NEJM, 2014