Malaria is one of the world’s most prevalent serious infectious diseases, with approximately 250 million cases and 1 million deaths per year (WHO, 2009). Mortality is primarily in children under the age of five and in pregnant women. Every 45 seconds, an African child dies of malaria. The disease is transmitted from person to person by infected mosquitoes, so past eradication efforts involved massive insecticide campaigns. These were successful in the Southeast U.S. for example, but failed in most poorly developed tropical countries. Current efforts involve distribution of bednets, particularly bednets impregnated with insecticide, to prevent mosquito bites at night. However, resistance to insecticides and to anti-malarial drugs for both prevention and treatment is rapidly rising. Thus, the need for a malaria vaccine is imperative for protection of millions of people from disease.
The malaria disease-causing organism is Plasmodium falciparum, and to a lesser extent, P. vivax. Both parasites undergo multiple transformations during their life cycle in mosquitoes and in various cell types and organ systems in the human host. Several malaria proteins have been used individually as vaccines with sporadic results. A current Phase III clinical malaria vaccine trial in Africa conducted by a large commercial vaccine company, uses a proprietary adjuvant. The best results so far reduced clinical episodes by 53% in vaccinated children, but protection only lasted for 8 months. This commercial vaccine is clearly unsuitable for Africa in terms of efficacy, cost and duration of immunity, but could be a profitable travelers’ vaccine.
The GVI adjuvant has the potential to significantly improve malaria vaccines. First, physical association of the adjuvant and antigen is not required, making it possible to rapidly evaluate the effectiveness of immunogens individually and in combination. Second, unlike other known adjuvants, the GVI adjuvant enhances and qualitatively improves the humoral antibody response and produces balanceed antibody and cellular immunity.Therefore, we feel that the GVI adjuvant is ideally suited for use in vaccines to parasites such as malaria.
Collaborative experiments with the Walter Reed Army Institute for Research (WRAIR) have been extremely encouraging. A malaria protein supplied by WRAIR was simply mixed with the GVI adjuvant and administered to mice. Compared with the protein alone, the immunogen plus adjuvant gave an immune response that was at least 50 times higher. This is all the more impressive considering that the dose of protein in the adjuvanted group was 60% less than in the group that received the protein alone. This experiment has been successfully repeated, and serum samples shipped to WRAIR showed anti-malarial activity in laboratory assays. The immunized mice themselves also have been supplied to WRAIR and directly challenged with parasite infected mosquitoes. A high level of protection was observed, and protection was maintained in immunized animals through at least six months. An experiment using two different malarial antigens plus adjuvant is planned.
The GVI portion of this Program has been funded through our NIH grant for general development of the adjuvant. We are developing plans for a comprehensive program:
- To assemble a multivalent malaria protein cocktail with representative antigens from the various life stages of P. falciparum and P. vivax
- To discover new protein targets that may induce protection against both of the major malaria types
- To test these proteins combined with the GVI adjuvant in animal models for induction of immune responses and protection against challenge. When the current round of mouse experiments is completed, we intend to present our ideas and funding needs to various interested agencies.