Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion...

Area of Science:

• Immunology
• Microbiology
• Vaccine Development

Background:

• The United States has seen a rise in pertussis (whooping cough) cases despite high vaccination rates.
• The shift to acellular pertussis vaccines has coincided with this resurgence, highlighting the need for more effective vaccines.

Purpose of the Study:

• To identify Bordetella pertussis antigens that are immunogenic and essential for bacterial persistence in the airway.
• To discover potential targets for improved pertussis vaccines that reduce bacterial carriage.

Main Methods:

• Immunoproteomics was used to identify B. pertussis antigens recognized by baboon serum and nasopharyngeal wash.
• Transposon-directed insertion-site sequencing (TraDIS) identified genes critical for bacterial persistence in the baboon airway.
• Subcellular localization of identified antigens was predicted.

Main Results:

• A total of 314 antigens were identified by convalescent baboon serum and 748 by nasopharyngeal wash.
• Thirteen B. pertussis antigens were found to be immunogenic in baboons, essential for airway persistence, and located in the cell membrane.
• These key antigens include OmpP, Pal, OmpA2, BamA, Pcp, MlaA, YfgL, MlaD, ComL, and several others.

Conclusions:

• The identified membrane-localized antigens are critical for B. pertussis persistence.
• These antigens represent promising candidates for inclusion in future pertussis vaccines aimed at preventing or reducing bacterial carriage.