Cross Protective Dengue Vaccine
Maxygen's MAXY-1500 has the potential to prevent Dengue fever, a disease that affects millions of people. We have used MolecularBreeding™ directed evolution to create antigens that include antigenic components from each of the four types of Dengue virus. This may reduce or eliminate the antigenic competition seen in prior "mixed antigen" approaches. Preliminary results with Maxygen's Dengue vaccine candidates show that they are cross protective.  Mouse immunization studies with Maxygen's Dengue vaccine candidates generate antibodies that react with and neutralize growth of all four types of Dengue virus in vitro. Maxygen's cross-protective Dengue vaccine is currently in preclinical development.

The Aedes aegypti mosquito transmits four types of Dengue virus. In general, the disease is extremely debilitating, resulting in high fever, severe headache, joint pain and lethargy. Dengue hemorrhagic fever (DHF) is a particularly serious form of the disease that can result when a patient has been infected with one type of Dengue virus then subsequently becomes infected with another type. It is therefore imperative that any Dengue vaccine protect against all four types of dengue (Types 1,2,3,4). Previous attempts at creating a cross-protective vaccine have been largely unsuccessful because the antigens from one type will tend to dominate, or "mask" the others, producing an incomplete immune response across the four types.

Scope
More than 50 million cases of dengue occur worldwide each year, resulting in nearly one million cases of dengue hemorrhagic fever (DHF). Fatalities due to DHF total 20,000 to 25,000 annually and approximately 500,000 cases require hospitalization. Dengue is an endemic disease in more than 100 countries in South America, Mexico, the Caribbean, the Eastern Mediterranean, South East Asia, the Western Pacific and Africa. The incidence, as well as the geographic distribution of Dengue, has grown dramatically over recent decades, and epidemics are increasing in frequency and severity.  Dengue fever cases have also been reported in 2002 in Hawaii.  A dengue vaccine would be useful broadly for travelers (tourist, business, military) to tropical and subtropical areas as well as for local populations.

Current estimates for annual sales of a cross-protective Dengue vaccine are in excess of $200 million.

Strategy
The development of MAXY-1500 was funded by the U.S. government.  The data that we have generated in this program so far is very encouraging, not only because of the opportunity to potentially prevent a disease that affects millions of people, but also because it indicates our technologies may be used to develop vaccines for other diseases characterized by pathogens with multiple infectious strains, such as HIV, HPV, Hepatitis C and influenza.  As part of Maxygen's increased focus on high-value protein pharmaceuticals announced in 2002, Maxygen is currently seeking corporate or philanthropic funding for this project.

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