Apicoplast-Deficient, Attenuated Strains of Plasmodium for Use as Malaria Vaccines

Tech ID: 21629 / UC Case 2011-116-0

Background

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans.

Technology Description

Researchers at UCSF and Stanford have developed a straightforward chemical method for generating live, attenuated apicoplast-deficient blood-stage malaria parasites. The attenuated strains can be used as malaria vaccines to induce immune responses after administration of the live, attenuated Plasmodium parasite or erythrocytes infected with the live, attenuated Plasmodium parasite. The major advantage of this approach is that the attenuation is achieved chemically and does not require genetic manipulation, thus allowing development of immunogenic vaccines against clinically relevant, circulating field strains of Plasmodium. Furthermore, this approach leads to the irreversible loss of the apicoplast, thereby eliminating the risk of genetic reversion or resistance. The resulting attenuated malaria parasite lacks critical metabolites synthesized by the apicoplast and is dependent on exogenous factors. When these factors are missing, the parasite cannot complete their life cycle and die. Loss of the apicoplast genome is easily validated by quantitative PCR following chemical treatment and rescue. Apicoplast-deficient strains may be proliferated indefinitely and grown in large quantities in the presence of required factors in vitro. This chemical method can also be applied to Plasmodium parasites that infect other mammalian species for testing of vaccine candidates.

The attenuated blood-stage malaria parasites can also be used in pathway-specific drug discovery screens for the development of anti-malarials. Drug candidates can be specifically identified or validated to target pathways involved in the function, replication and maintenance of the apicoplast. 

Current and future work is focused on validating attenuated vaccine candidates using in vivo models for rodent and human malaria.

Advantages and Suggested Uses

  • Development of live, attenuated blood-stage malaria vaccines against human malaria parasites such as P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi.
  • Chemical method causes irreversible loss of the apicoplast, yet retains full growth in vitro, but not in vivo.
  • No risk of resistance.
  • Chemical approach allows development of vaccines against field strains of Plasmodium and can be easily implemented in malaria-endemic regions.
  • Vaccine candidates can be tested in animal malaria models using the same chemical method.
  • Drug discovery: Attenuated blood-stage malaria parasites can be used in cell cultured-based, pathway-specific drug discovery screens.

Related Materials

Contact

Learn About UC TechAlerts - Save Searches and receive new technology matches

Inventors

  • DeRisi, Joseph L.
  • Yeh, Ellen

Other Information

Keywords

malaria, vaccine, anti-malarial, Plasmodium, drug discovery, drug screening

Categorized As