Dengue Vaccine Development
In the absence of truly effective and sustainable vector control measures, a dengue vaccine is urgently needed. While dengue vaccines have been under development since the 1940s, due to the limited appreciation of global dengue disease burden and of the potential markets for dengue vaccines, the industry’s interest languished throughout much of the 20th century.
In recent years, however, the development of dengue vaccines has accelerated dramatically. Sanofi Pasteur’s Dengvaxia® became the first dengue vaccine to be licensed for use in 2015. Today, several other vaccines are in various stages of advanced development, with clinical trials currently underway.
Vaccine development for dengue is particularly challenging because dengue fever is caused by any of four related, but distinct, virus serotypes (DENV-1-4). While infection by one virus provides lifelong immunity against that serotype, it provides only partial and transient immunity against the other three. This means that an effective vaccine against dengue should be tetravalent, providing protection against all four dengue viruses.
Recent findings have revealed another challenge: vaccination by the first licensed dengue vaccine can increase the risk of severe dengue in people of all ages who have not had prior dengue infection (i.e., are seronegative). The Strategic Advisory Group of Experts (SAGE) on Immunizations, an independent group that advises the World Health Organization (WHO), recommended that, in order to maximize public health impact and minimize harm, pre-vaccination screening should ideally be performed on prospective Dengvaxia recipients, and that only those individuals having evidence of previous dengue infection (i.e., are seropositive) should be vaccinated. A difference in vaccine performance based on serostatus is theoretically possible for all live dengue vaccines.
There is also no correlate of protection, which is a measurable sign (such as antibodies) that a person is immune, and no laboratory animal models available that reliably predict that a vaccine will protect a person against dengue.
These are some of the issues that GDAC members are addressing through workshops and other initiatives.
Dengue vaccines will complement, but not replace, prevention methods, such as vector control, already in place. According to the WHO, drawing on the experiences of other vaccine-preventable vector-borne diseases, effective surveillance, prevention and outbreak response tools (vector control and vaccines) must continue to complement each other in reducing the burden of the disease.