Infectious plasmodium sporozoites grown in vitro

Inventors

EAPPEN, Abraham G. • Hoffman, Stephen L.

Assignees

Sanaria Inc

Abstract

The application is directed to in vitro-reared Plasmodium sporozoites of human host range wherein sporogony from gametocyte stage to sporozoite stage is external to mosquitoes, and methods of producing the same. Provided herein are in vitro-reared infectious Plasmodium sporozoites (SPZ) of human host range, particularly P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi, wherein sporogony from gametocyte stage to sporozoite stage is external to mosquitoes, and methods of producing the same.

Core Innovation

The document describes in vitro-reared infectious Plasmodium sporozoites of human host range in which sporogony from gametocyte stage to mature sporozoite stage is external to mosquitoes. The in vitro-reared infectious Plasmodium sporozoites are provided absent any mosquito material, including embodiments without mosquito-derived attendant material, and the disclosed compositions and uses are directed to Plasmodium-specific antigens and immune response induction in human hosts.

The background contrasts mosquito-intensive manufacture of Plasmodium sporozoites with prior in vitro attempts, which are described as having limited infectivity performance. The document presents the problem as achieving infectious Plasmodium sporozoites and effective potency comparable to mosquito-derived Plasmodium sporozoites while shifting the sporogony process external to mosquitoes.

The described embodiments include compositions and vaccine compositions comprising the in vitro-reared infectious Plasmodium sporozoites with pharmaceutically acceptable diluents or excipients, and they further specify aseptic conditions. The document also describes performance as marked increases in oocyst production in vitro versus mosquitoes, production of infective Plasmodium falciparum sporozoites, and hepatocyte infectivity comparable to mosquito-derived Plasmodium falciparum sporozoites.

Claims Coverage

The independent claims cover four inventive features: a composition, a vaccine composition, a method of inducing an immune response in a human subject, and in vitro-reared infectious Plasmodium sporozoites that are attenuated. Across the independent claims, the inventive features include external-to-mosquito sporogony, absence of mosquito material, aseptic sporozoites, and attenuated sporozoites.

Across the independent claims, the core coverage centers on in vitro-reared infectious Plasmodium sporozoites of human host range where sporogony is external to mosquitoes, in formulations that exclude mosquito material, and in certain embodiments require aseptic sporozoites or specify attenuated sporozoites. The independent claims further support vaccine compositions and methods for inducing an immune response against Plasmodium-specific antigens in human subjects.

Stated Advantages

Documented Applications