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The technology includes modifying the Plasmodium falciparum Pfs48/45 Domain III protein sequence to enhance its stability and efficacy to aid in malaria vaccine development. This approach successfully overcomes previous production challenges by increasing the thermostability of the antigen and eliminating the need for additional modifications that could impair vaccine effectiveness. Crucially, the technology maintains the essential neutralizing epitope of Pfs48/45, ensuring its effectiveness in preventing malaria transmission as a transmission-blocking vaccine.

This technology encompasses the development of highly advanced malaria vaccine candidates and human monoclonal antibodies, both centered on targeting the Merozoite Surface Protein 1 (MSP1) of the Plasmodium falciparum malaria parasite. The innovation lies in utilizing a novel computational design and in vitro screening process, which has created MSP1 vaccine candidates that are significantly more immunogenic, stable, and cost-effective than existing alternatives. These vaccines focus on the 19 kDa carboxy-terminus fragment of MSP1.

This technology focuses on the creation of single-component AMA1-RON2 (Apical membrane antigen 1-rhoptry neck protein 2) vaccine candidates. These candidates are based on a novel composition of matter designed to elicit a more effective immune response against the malaria parasite Plasmodium falciparum. The standout aspect of this technology is the Structure-Based Design 1 (SBD1) immunogen, engineered through a structure-based design that significantly enhances its ability to produce potent, strain-transcending neutralizing antibodies.

The Plasmodium parasite has a complex lifecycle during human infection and in the mosquito vector. Most advanced malaria vaccine candidates can confer only partial, short-term protection in malaria-endemic areas. A means of breaking the transmission of malaria to subsequent individuals could prevent a significant amount of human disease.

The primary embodiments of this technology are novel compositions of matter that produce enhanced transmission-blocking responses over current transmission blocking vaccines:

Using proteins derived from the malaria Plasmodium falciparum parasite, NIAID has developed three different nanoparticle platforms to serve as scaffolds for displaying multiple copies of malaria antigens in an organized, repetitive manner to enhance vaccine effectiveness. The first platform uses the pyridoxal 5’-phosphate (PLP) synthase protein to form a nanoparticle displaying 48 copies of up to 4 different proteins. The second platform uses the chaperone 60 (Cpn60), which can display 28 copies of up to 2 different proteins.

The technology focuses on the development of a tetravalent bispecific antibody effective against Bacillus anthracis, the bacterium responsible for anthrax. This antibody combines the specificities of two monoclonal antibodies (mAbs): one targeting anthrax protective antigen (PA) and the other targeting the bacterial capsule. The anti-PA mAb shows potent toxin-neutralizing activity, while the anti-capsule mAb efficiently kills anthrax bacteria.

Enterovirus D68 (EV-D68) has been linked to the widespread outbreaks of respiratory illness and acute flaccid myelitis (AFM) in the United States and Europe in 2014, 2016, and 2018. Although EV-D68 is now the most frequently encountered enterovirus (41.1% of cases), with an estimated global prevalence of 4%, there are no specific, FDA-approved therapeutic interventions targeting this virus.