CHOP researchers identify two proteins that could be used for a potential NTHi vaccine

Scientists at the Children’s Hospital of Philadelphia (CHOP) have identified two proteins that could be used for a potential vaccine against non-typables Haemophilus influenzae (NTHi). Working in a mouse model, researchers found that administration of two bacterial adhesive proteins that play a key role in helping bacteria attach to respiratory cells and initiate respiratory tract infection boosted protective immunity against various NTHi strains, highlighting the potential of the vaccine.

The results were published today in the Proceedings of the National Academy of Sciences.

Not typable Haemophilus influenzae is the most common cause of bacterial respiratory tract infections such as middle ear infections, sinus infections, and exacerbations of chronic obstructive pulmonary disease (COPD) and other underlying lung diseases, resulting in significant morbidity in children and adults. This organism is also an important cause of invasive diseases such as sepsis and meningitis. Currently, there are no vaccines or other approaches to protect against infection with this organism. Our study identified two proteins that stimulate both an antibody response and a broader cellular immune response that protect against various strains of NTHi influenza and therefore may be useful for inclusion in a vaccine to protect against a full range of NTHi disease.”

Joseph W. St. Geme, MD, lead study author, chief medical officer, and chair of the pediatrics department at the Children’s Hospital of Philadelphia

Because there are so many strains of NTHi, it has been difficult to develop a vaccine that protects against infection. Surface antigens, which are generally used for immunization, vary from strain to strain, and thus antibodies against one strain of NTHi often do not protect against another strain.

To get around this challenge, the researchers focused on HMW1 and HMW2, two high molecular weight adhesive proteins involved in NTHi colonization of the nasopharynx, the first step in the pathogenesis of NTHi disease. These adhesive proteins are exposed on the surface of bacteria and are present in approximately 75-80% of NTHi strains.

Using a mouse model, the researchers found that immunization with HMW1 and HMW2 stimulated the production of protective antibodies against the strain of NTHi from which the adhesive proteins were derived. Although the antibodies are specific to the parent strain of NTHi, the researchers found that immunization with HMW1 and HMW2 also offered protection against bacterial colonization by other NTHi strains, resulting in the stimulation of the mediated immunity. cellular and interleukin production 17.

“These results indicate that the mice were protected against infection by heterologous strains, despite a strain-specific antibody response,” said St. Geme. “Taken together, the results of this study highlight the vaccine potential of the HMW1 and HMW2 proteins. “