Anti-malarial compositions
Inventors
Gutierrez, Gabriel M. • Pannucci, James • Noe, Amy • Huang, Steve Chienwen • Winram, Scott • Mo, Annie Xiaoyan
Assignees
Leidos Inc • US Department of Health and Human Services
Publication Number
US-10160802-B2
Publication Date
2018-12-25
Expiration Date
2033-12-05
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Abstract
This disclosure provides antibodies that are useful for preventing and/or treating malaria. The epitope to which the antibodies bind is in close proximity to the conserved proteolytic cleavage site of P. falciparum circumsporozoite protein (CSP), and the antibodies provided in this disclosure can prevent cleavage and inhibit P. falciparum sporozoites from invading the liver.
Core Innovation
This disclosure provides antibodies that bind to an epitope in close proximity to the conserved proteolytic cleavage site of Plasmodium falciparum circumsporozoite protein (CSP). The antibodies, including the monoclonal antibody 5D5, can prevent cleavage at this site and inhibit P. falciparum sporozoites from invading the liver, thereby preventing or treating malaria infections.
The problem being solved is the need for effective methods to prevent and treat malaria by targeting a critical step in the parasite's infection process. Plasmodium sporozoites invade human liver cells after circumsporozoite protein (CSP) is proteolytically cleaved at a highly conserved pentapeptide cleavage site. Inhibition of this cleavage can reduce parasite liver invasion, a crucial stage for malaria infection establishment.
Claims Coverage
The claims cover three main inventive features relating to cDNA molecules encoding antibody variable regions with specific complementarity determining regions (CDRs).
cDNA molecule encoding heavy chain variable region with specific CDRs
The cDNA molecule comprises a coding sequence for a heavy chain variable region of an antibody containing the first, second, and third heavy chain complementarity determining regions (CDRH1, CDRH2, CDRH3) with sequences SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 respectively, or corresponding to the antibody deposited under Accession No. MRA-1242.
cDNA molecule encoding light chain variable region with specific CDRs
The cDNA molecule comprises a coding sequence for a light chain variable region of an antibody containing the first, second, and third light chain complementarity determining regions (CDRL1, CDRL2, CDRL3) with sequences SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6 respectively, or corresponding to the antibody deposited under Accession No. MRA-1242.
Combination of heavy and light chain variable region cDNA molecules
A cDNA molecule comprising a coding sequence for a heavy chain variable region and also for a light chain variable region together, both comprising the complementarity determining regions of the antibody deposited under Accession No. MRA-1242.
The claims principally cover cDNA molecules encoding heavy and light chain variable regions of antibodies, specifically those with CDR sequences as defined and corresponding to the deposited monoclonal antibody 5D5, which targets a conserved epitope near the CSP cleavage site of Plasmodium falciparum.
Stated Advantages
The antibodies can prevent cleavage of CSP and inhibit Plasmodium sporozoite liver invasion, thereby reducing or preventing malaria infection.
The conserved nature of the cleavage site across Plasmodium species allows for broad use of the antibodies in treating infections by multiple human-infecting Plasmodium species.
Documented Applications
Prophylactic administration to malaria-naïve individuals entering endemic regions to reduce or prevent infection.
Therapeutic administration to treat individuals already infected with Plasmodium species.
Use in combination with traditional malaria vaccines to enhance immune response against Plasmodium.
Use in combination with other anti-malarial drugs such as atovaquone and proguanil, chloroquine, doxycycline, mefloquine, and primaquine.
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