Antibody-based immunoprophylaxis antimalarial therapy
JHU REF: [C12545]
Invention novelty: an improved antibody-based malarial therapy
Value Proposition
Malaria remains one of the world’s major causes of death, especially in Africa. Ninety percent of malaria mortalities occur in Africa, where it accounts for about one in five childhood deaths. WHO reported that there were 216 million cases of malaria in 2010, with 655,000 deaths. The majority of cases (65%) occurred in children under 15 years of age. WHO estimates that 3.3 billion people, or approximately half of the world’s population, are at risk of contracting malaria. In humans, malaria infection is caused by one or more of four species of intracellular protozoan parasites: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. There are currently no effective malaria vaccines available.
Previous attempts for a malaria vaccine have fallen short of expectations, in part due to inability to induce durable high-titer antibodies. A single un-neutralized sporozoitecan initiate infection, necessitating sustained high-titer neutralizing antibodies for lasting protection. Advantages of current technology include:
• the ability to generate a high-titer antibody response in mice upon vaccination
• antibody response to malaria vaccine developed early and persisted
Technical Details
Johns Hopkins researchers developed a therapy for malaria based on antibody-based vectored immunoprophylaxis. Recently, Dr. David Baltimore’s group at California Institute of Technology has developed an adeno-associated virus serotype 8 (AAV8) platform to deliver pre-formed monoclonal antibodies in vivo. Mice injected with a single intramuscular dose of AAV2/8 expressing a neutralizing HIV monoclonal antibody produced high-titer antibody expression for at least 52 weeks. Humanized mice were protected against an HIV challenge as monitored by CD4+ T cell loss. In collaboration with Dr. Baltimore’s lab, the inventor has developed and administered to mice an AAV8 vector expressing either 2A10 or 2C11 humanized monoclonal antibodies that recognize the circumsporozoites (CSP) protein of P. falciparum. Mice developed high titer human IgG antibodies as early as 1 week post inoculation, persisting for at least 8 weeks. Antibody levels exceed those previously shown to protect mice from a malaria challenge. Thus, this vectored immunoprophylaxis (VIP) has the potential to be an effective form of malaria control.
Stage of Development: Pre-Clinical
Publication(s)/Associated Cases: PMC4151717
