Sanofi Pasteur announce results of Ph. 3 dengue vaccine trial

On 03 September, Sanofi Pasteur announced in a press release the preliminary results of a Phase 3 study of their tetravalent dengue vaccine in Latin American children. It showed an overall reduction in disease cases of 61%, with efficacy against the four serotypes as: Type 1 – 50%, 2 – 42%, 3 – 74%, and 4 – 78%. It also showed reduction in hospitalisation of 81%. This is a partner study to a similar one carried out in Thailand and recently cited as in press in the Lancet (Capeding et al. doi: 10.1016/S0140-6736(14)61060-6). The Thai study showed protective efficacy of 57% overall. A full analysis of the efficacy and safety data from this study is yet to be completed and the full results will be published in a peer-reviewed journal and presented at the American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting in November.

These study results are promising. Dengue is rapidly becoming as large a health issue in the central tropical belt through Latin America, Central Africa, South & South-East Asia as malaria. Governments in these countries are under pressure to divert scarce resources away for the fight against malaria to tackling dengue, especially as there is no vaccine and treatment is primarily supportive. Having an effective vaccine would go a long way to stemming the spread of the disease that is also to be found in Northern Australia and the Southern United States – wherever the vector, the Aedes mosquito, can be found. (See http://apps.who.int/ithmap/). The history of the development of a dengue vaccine is a long one, with many failures along the way. There was considerable concern in 2012, when the results of the Ph. 2b study on the vaccine was published (Sabchareon et al. doi: 10.1016/S0140-6736(12)61428-7). Unexpectedly this study only showed 30% efficacy, with no effect against the Type 2 serotype. It has been something of a relief that the larger Ph. 3 studies seem to have overcome the problems found in the 2012 study.

It appears though that the Type 2 serotype remains the most difficult to protect against. It is distinct from the others with low sequence homology to the other three types (see Henchal & Putrak doi: 10.1128/cmr.3.4.376). It is also the more prevalent strain in South-East Asia. There must be care in ensuring that any vaccine that is ultimately deployed has enough protection against all four serotypes. While infection with one serotype gives life-long immunity against that type, there is no lasting cross-protection to the others. There has been some concern that a previous dengue infection with one serotype may be a precipitating factor in the development of dengue haemorrhagic fever, which is potentially much more life-threatening.

The Sanofi Pasteur press release can be found at: Press Release