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AKAGERA MEDICINES INC
WALTHAM, MA, 02452
Unclaimed
Small Business
Subcontracting experience
1 record from government sources. Past participation is not evidence of current teaming interest.
| Role | Agency | Description | Vehicle | Obligated | Action date | Period |
|---|---|---|---|---|---|---|
| Subcontractor | Department of Health and Human Services | STATEMENT OF WORK: DEFINING THE ROLE OF CD8 T CELLS INDUCED BY A NOVEL LIPOSOMAL NANOPARTICLE MRNA VACCINE IN PREVENTING MYCOBACTERIUM TUBERCULOSIS INFECTION.
THE GOAL OF IMPAC-TB IS TO IDENTIFY MECHANISMS OF PROTECTIVE IMMUNITY AGAINST TB, AND OUR OVERALL STRATEGY FOR THE CASCADE IMPAC-TB ANIMAL PROGRAM IS TO START WITH GOLD-STANDARDS OF VACCINE-MEDIATED PROTECTION (I.E, CMV/TB AND IV BCG IN NHP; BCG IN MICE) AND THEN DISSECT HOW PROTECTION IS MEDIATED. THE AKAGERA MRNA VACCINE REPRESENTS A NEW GOLD STANDARD FOR PREVENTION OF INFECTION €€Œ THE BEST VACCINE-MEDIATED PROTECTION EVER OBSERVED IN MICE. TO ACHIEVE OUR GOAL OF IDENTIFYING MECHANISMS OF TB IMMUNITY, CASCADE IMPAC-TB WOULD LIKE TO IDENTIFY THE ANTIGENS AND T CELL SUBSETS THAT MEDIATE THE PROTECTION PROVIDED BY THE NEW AKAGERA MRNA VACCINE, WHICH SHOWS THE BEST VACCINE-MEDIATED PROTECTION EVER OBSERVED IN MICE.
THE SPECIFIC WORK TO BE PERFORMED IS DETAILED BELOW. UNDER ALL THREE AIMS, AKAGERA MEDICINES WILL BE RESPONSIBLE FOR CREATING THE MRNA VACCINE CONSTRUCTS REQUIRED FOR EACH EXPERIMENT. IN ADDITION, SCIENTISTS AT AKAGERA MEDICINES WILL ALSO MEET REGULARLY WITH SCIENTISTS AT SCRI TO EVALUATE PROGRESS, DESIGN NEW CONSTRUCTS, AND TROUBLE-SHOOT, AS NECESSARY.
AIM 1: IDENTIFY PROTECTIVE ANTIGENS IN THE AKAGERA MRNA VACCINE.
AKAGERA MEDICINES WILL PREPARE SEPARATE MRNA VACCINE CONSTRUCTS FOR 4 ORFS (TB10.4, MTB39, AND ESAT-6 WHICH ARE THE MOST IMMUNOGENIC ANTIGENS IN THE MRNA VACCINE, AND MTB32, WHICH ALONG WITH MTB39 IS PART OF THE M72 VACCINE). THESE WILL BE SENT TO SCRI FOR TESTING IN MICE, TO COMPARE THE PROTECTIVE EFFICACY OF THE PARENTAL MRNA VACCINE, EACH OF THESE 4 CONSTRUCTS INDIVIDUALLY, POOLED ADMINISTRATION OF TB10.4, MTB39, ESAT-6 MRNA CONSTRUCTS, AND THAT SAME POOL WITH THE ADDITION OF MTB32. SCRI WILL MEASURE THE THREE METRICS OF IMMUNITY THAT WERE PREVIOUSLY DEFINED IN THE ULD MODEL: REDUCTION OF LUNG BACTERIAL BURDENS, PREVENTION OF DISSEMINATION TO THE CONTRALATERAL LUNG, AND PREVENTION OF DETECTABLE INFECTION. COLONIES WILL BE COLLECTED, DNA ISOLATED, AND BAR-CODES AMPLIFIED AND SEQUENCED TO DETERMINE THE NUMBER OF FOUNDING MTB STRAINS IN EACH LUNG. BECAUSE THE GROUP SIZES WILL HAVE TO BE REDUCED TO 15 MICE (RATHER THAN OUR MORE STANDARD 20) TO ACCOMMODATE THE NUMBER OF VACCINES TESTED SIMULTANEOUSLY, THE EXPERIMENT WILL BE REPEATED FOUR TIMES TO ASSURE REPRODUCIBILITY AND STATISTICAL RIGOR. IF PROTECTION CONFERRED BY THE THREE OR FOUR POOLED ANTIGENS IS NOT SIMILAR TO THAT CONFERRED BY THE PARENT VACCINE, AKAGERA MEDICINES WILL SYNTHESIZE ADDITIONAL ANTIGENS UNTIL A COCKTAIL OF ANTIGENS THAT CONFERS SIMILAR PROTECTION IS FOUND.
AIM 2: IDENTIFY AND ELIMINATE CD8 EPITOPES FROM MRNA VACCINE CONSTRUCTS.
THIS AIM WILL FOCUS ON EACH ANTIGEN THAT CONFERRED SOME DEGREE OF PROTECTION AGAINST ESTABLISHING SUSTAINED INFECTION IN AIM 1. ANTIGENS THAT DID NOT PREVENT DETECTABLE INFECTION WILL NOT BE EXAMINED FURTHER IN AIM 2. IN PRIOR CD8 EPITOPE MAPPING STUDIES, TB10.4 IS KNOWN TO HAVE TWO EPITOPES, TB10.4 ON THE H-2B BACKGROUND (C57BL/6) AND TB10.4 ON THE H-2D BACKGROUND (BALB/C), AND MTB32A IS KNOWN TO HAVE ONE EPITOPE ON THE H-2B BACKGROUND (C57BL/6) (MTB32). THUS, IF THESE ANTIGENS ARE FOUND TO CONTRIBUTE TO PREVENTION OF INFECTION IN AIM 1, AKAGERA MEDICINES WILL MAKE A TRUNCATED TB10.4 OR MTB32A CONSTRUCT THAT LACKS THE RESPECTIVE CD8 EPITOPES, BUT WHICH WOULD STILL CONTAIN KNOWN CD4 EPITOPES. FOR MTB39 AND ESAT6, THE CD8 EPITOPES HAVE NOT BEEN MAPPED, BUT IF EITHER MTB39 OR ESAT-6 WERE SHOWN IN AIM 1 TO CONTRIBUTE TO PREVENTING INFECTION, AKAGERA WOULD GENERATE OVERLAPPING PEPTIDES FOR EACH ANTIGEN AND MAP THE EPITOPE(S) RESPONSIBLE USING STIMULATIONS ASSAYS WITH SPLENOCYTES FROM IMMUNIZED B6XBALB/C F1 MICE. AFTER IDENTIFYING THE EPITOPES, AKAGERA MEDICINES WOULD GENERATE NEW CONSTRUCTS THAT SPECIFICALLY LACKED THE CD8 EPITOPES, EITHER VIA TRUNCATION OR POINT MUTATION OF AMINO ACID RESIDUES PREDICTED TO BE CRITICAL FOR THE RESPONSE.
MICE WOU 13492SUB Parent award context Parent award agency: Department of Health and Human Services · National Institutes of Health Parent award NAICS: 541714 Parent award performance state: WA Parent award description: IMMUNE MECHANISMS OF PROTECTION AGAINST MYCOBACTERIUM TUBERCULOSIS CENTER (IMPAC-TB) View parent award on USAspending | — | $107,341 | Jan 31, 2025 | — – — |
Contract vehicles are shown only when present in the source record. Linked award numbers and vehicles open the authoritative record on USAspending.gov.