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Publication No: IN202311053048 [India] Application No: 202311053048
Title: Live genetically attenuated parasite as malaria vaccine
Publication Date: 14-02-2025 File Date: 07-08-2023
Inventor(s): Satish Mishra; Sunil Kumar Narwal; Ankit Ghosh; Akancha Mishra
IPC Classification: A61K 39/00, A61K 39/015, C07K 14/445, A61P 33/06, C07K 16/20
Abstract:
The present invention relates to live genetically attenuated parasite as malaria vaccine. The invention provides Plasmodium knockout parasites to  immunize vertebrate hosts that suffer arrested development in the liver and do not produce merozoites. We found that rodent malaria parasite Plasmodium berghei  lacking Stearoyl-CoA delta 9 desaturase (SCD) or Sporozoite Conserved Orthologous Transcript (SCOT1) arrest at a late step in liver stage development and do not  form merozoites. Mutant parasites infect the liver but cannot develop to a disease-causing blood stage infection allowed us to test their potential as live-attenuated  vaccines. Mice immunized with sporozoites that lack the genes SCD, or SCOT1 are protected against subsequent challenge with infectious sporozoites. SCD, or SCOT1  mutants failed to initiate blood stage infection at optimal sporozoites dose but when mice were inoculated with high doses, rare breakthrough infection was observed.  Therefore, for safety measure and to achieve full attenuation, we generated SCD/SCOT1 GAP, which was safe at very high doses of sporozoites. SCD/SCOT1 late liver  stage-arresting P. falciparum GAP would give us a new gold standard for a malaria vaccine.
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