Haemophilus influenzae (H. influenzae) colonizes in the upper respiratory tract causing a wide variety of diseases, including otitis media, conjunctivitis, sinusitis, pneumonia, and meningitis. H. influenzae strains are classified into 6 serotypes depending on antibody specificity to the bacterial capsule. There is also a genetically diverse group of strains that do not express a capsule, termed non-typeable H. influenzae (NTHi). NTHi is now one of the leading causes of otitis media in children and exacerbation of chronic obstructive pulmonary disease (COPD) in adults. Current efforts in NTHi vaccine development focus on generating antibodies against surface antigens, but have had limited success due to the antigenic diversity among NTHi strains.
Dr. Hao Shen discovered that a cellular response from CD4 T-cells (Th17) is the required immune mechanism of protection against NTHi lung infections and is broadly protective against different NTHi strains, unlike antibody responses that are highly strain specific.
Drs. Hao Shen and Brian Akerley discussed screening for conserved NTHi antigens recognized by T-cells, and Dr. Akerley developed a list of conserved NTHi proteins based on published genomic data as potential target antigens. Dr. Shen screened these proteins and identified conserved protein antigens that are recognized by Th17 during NTHi infection, including protein antigens 0259 and 0264 that are conserved among 97% of NTHi strains.
Dr. Shen showed that immunization with protein antigens 0259 and 0264 induce antigen-specific Th17 cellular responses that recognize different NTHi strains and protect against the lung infection. Therefore, immunization with these protein antigens provide broad protection against infections by different NTHi strains.
- Non-typeable H. influenzae vaccine
- Protective against influenza co-infections
- Broadly protective against different strains of NTHi; not limited to strain-specific surface antigens
- Can be effectively administered subcutaneously, intramuscularly, intraperitoneally, or intravenously
Stage of Development:
- Target identified
- Preclinical proof of concept
Provisional application filed
Li, Wenchao et al.; PNAS July 2014, 2018; 115(30); E7149.
Docket # 19-8990