Development of a recombinant vaccine against Dengue virus

Therapeutic area

Goal

Achievement of a preventive vaccine composition against all serotypes of Dengue viruses (DEN-1, DEN-2, DEN-3, DEN-4).

Description

The Dengue virus produces Dengue fever and in some cases a very severe disease with a high mortality rate: the Hemorrhagic Dengue fever. These diseases have increased considerably after the 2 nd World War and are now considered the main arthropod born diseases in the tropical region.

The collaboration project is carried out between the CIGB and the Institute for Tropical Medicine “Pedro Kouri” (IPK). The main results obtained so far are:

• Expression in E. coli of the domain III from dengue envelope protein of each serotype fused to the P64k protein carrier. High levels of neutralizing and protecting antibodies were obtained in mice. The chimeric construct of DEN2 serotype induced solid protection in monkeys after homologous challenge measured by viral isolation.
• Expression in E. coli of Core protein. Protection mediated by cellular response has been achieved in mice. Preclinical trial on monkeys is ongoing.

Patent Status

1. Use of the N-terminal of P64k as expression system in Escherichia coli for heterologous antigens (CIGB). Filed in PCT, China, Brazil, Canada, Mexico, Japan, South-Korea, Republic, and Hungary. Issued in Cuba, EPO, United States, Australia and Israel.

3. Chimeric chains coding for proteins inducing effects against viruses. Preparations using chimeric proteins. Filed in Canada, India, China, South-Korea, Mexico, Brazil, Japan, Guatemala, Thailand and Malaysia. Granted in Europe, USA, Singapore, South Africa and Australia.

3. Induction of protective response by capsid protein of dengue 2 virus. Filed in USA, EPO, Canada, Japan, Australia, Brazil, Mexico, South Africa, India, South Korea, Russia, China, Argentina, Thailand, Indonesia, Malaysia, and Singapore.

Project Status

Development and preclinical. Production of vaccine candidates on cGMP facilities and preclinical trials in monkeys using different adjuvants for human use are ongoing.

Type of collaboration requested

• Partnership for clinical trials.
• Out-licensing agreement for specific territories.

Competitives advantages Milestones

Experience in vaccine research, highly skilled staff, and self-reliant reference laboratory. Strong intellectual property position. A vaccine candidate produced with highly purified recombinant proteins avoids possible viral contaminations and hence, being chemically defined, its safety pattern is superior to that of live-attenuated vaccines. The serotype-specificity associated to particular recombinant antigens is higher in this kind of subunit vaccine avoiding the immuno-enhancement problems.
The candidate vaccine can be very useful also as a booster formulation for prime-boost strategies. Development and preclinical will finish this year. Clinical trial phase I is planned next year.

Host Insitutions

Center for Genetic Engineering and Biotechnology (CIGB). Ave 31, e/158 y 190 Cubanacán, Playa. PO Box 6996, La Habana, 10600, Cuba. Tel. (53-7) 2712397; 2716022. Fax. (53-7) 2736008; 2718070. E-mail: ernesto.lopez@cigb.edu.cu
Web site: http://gndp.cigb.edu.cu

"Pedro Kouri" Institute of Tropical Medicine (IPK) Autopista Novia del Mediodía, Km 6, No 251, e/ Carretera Central y Autopista Nacional, Ciudad Habana. Fax: 53-7 336051.
E-mail:   lupe@ipk.sld.cu

BIO/CIGB/2008-03