**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AVIAN MYCOPLASMOSIS IS ONE OF THE MAJOR THREATS TO POULTRY AND EGG PRODUCTION WORLDWIDE. THE PRIMARY ETIOLOGIC AGENT, MYCOPLASMA GALLISEPTICUM (MG), BELONGS TO A GENUS OF INSIDIOUS AND OBLIGATE BACTERIAL PATHOGENS AGAINST WHICH EFFECTIVE AND WELL-DEFINED VACCINES ARE LIMITED OR LACKING. THOUGH NON-CLASSICAL VIRULENCE FACTORS HAVE BEEN IDENTIFIED OR IMPLICATED IN MG AND OTHER MEMBERS OF THE GENUS MYCOPLASMA, TOOLS FOR GENETICALLY MODIFYING MYCOPLASMAS ARE ALSO LIMITED OR LACKING, MAKING DEVELOPMENT OF RATIONALLY DESIGNED ANTI-MYCOPLASMA VACCINES DIFFICULT. DESPITE THIS SHORTCOMING, RECENT ADVANCES IN ASSESSING IN-VIVO GENE EXPRESSION LEVELS IN MG DURING INFECTION OF THE NATURAL HOST HAS PROVIDED VALUABLE INSIGHTS INTO RESPONSES OF THE PATHOGEN AS IT STRIVES TO COLONIZE THE HOST. KNOWLEDGE OF SPECIFIC VIRULENCE DETERMINANT EXPRESSION IN THE INITIAL AND MOST CRITICAL PHASE OF INFECTION IS, FOR THE FIRST TIME, MAKING FEASIBLE THE CONSTRUCTION OF A RATIONALLY DESIGNED ANTI-MG VACCINE. HERE WE PROPOSE TO FURTHER DEVELOP AND REFINE OUR NEWLY CONSTRUCTED SUBUNIT MG VACCINE BASED ON OUR KNOWLEDGE OF ESSENTIAL VIRULENCE DETERMINANTS. WE BELIEVE THAT THIS VACCINE WILL HAVE SUPERIOR EFFICACY AND DESIGN FLEXIBILITY NOT AVAILABLE WITH THE COMMERCIALLY AVAILABLE BACTERIN (MG-BAC®). OUR VACCINE MAINTAINS A HIGH SAFETY PROFILE AND NO POSSIBILITY OF REVERSION TO VIRULENCE THAT CAN OCCUR WITH LIVE ATTENUATED VACCINES. OUR VACCINE IS AMENABLE TO RAPID MODIFICATION VIA THE INCORPORATION OF ADDITIONAL MG VIRULENCE DETERMINANTS IF NEEDED, OR PROTECTIVE ANTIGENS FROM OTHER SIGNIFICANT AVIAN PATHOGENS SUCH AS MYCOPLASMA SYNOVIAE. THIS PROGRESSIVE FORMAT IS ANALOGOUS TO THE APPROACH EMPLOYED IN THE DEVELOPMENT OF THE STREPTOCOCCUS PNEUMONIAE VACCINE, PREVNAR WHICH INCORPORATES PURIFIED CAPSULAR POLYSACCHARIDES FROM 13 SEROTYPES CONJUGATED TO DIPHTHERIA TOXOID PROVIDING A BROAD RANGE OF COVERAGE FROM PATHOGENIC SEROTYPES OF S. PNEUMONIAE. WE ALL HAVE ALL WITNESSED THE IMPRESSIVE SPEEDOF DEVELOPMENT OF NOVEL AND EFFICACIOUS COVID-19 VACCINES. WHILE MRNA-BASED VACCINES (E.G. COVID-19 VACCINES FROM MODERNA AND PFIZER) ARE NOT YET ECONOMICALLY OR LOGISTICALLY PRACTICAL FOR APPLICATIONS IN ANIMALS, OUR PROPOSED VACCINE IS. AND SIMILARLY, OUR VACCINE CAN BE MODIFIED VERY RAPIDLY WITH RELEVANT GENE SEQUENCE INFORMATION FROM OUTBREAKS OR FIELD STRAINS OF M. GALLISEPTICUM.

University Of Connecticut, Storrs CT

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