Progress Towards a Mucosal Vaccine for Pneumonia

Pneumonia is a significant cause of death, responsible for more than 2.56 million deaths worldwide in 2017, over 800,000 of which were children. The disease can be caused by several different bacteria, viruses and fungi, with Streptococcus pneumoniae and Haemophilus influenzae type b being the most common bacterial causes in children. Although current immunization strategies against these pathogens are helping to reduce rates of infection and mortality, vaccines that can provide broader protection and be administered at mucosal sites are of growing interest.

In a new study published in Science Immunology, researchers describe a subunit mucosal vaccine that induces broadly protective immunity against Klebsiella pneumoniae strains – the leading cause of hospital-acquired pneumonia, for which there are currently no licensed vaccines. Technology Networks interviewed author Jay Kolls, MD, professor of medicine and pediatrics, John W Deming endowed chair in internal medicine, Tulane University School of Medicine, to learn more about the findings and their significance.

Anna MacDonald (AM): What led you to investigate a subunit mucosal vaccine strategy for pneumonia?

Jay Kolls (JK): Although we had efficacy data with heat killed bacteria and outer membrane vesicle-based vaccines, we thought a subunit-based vaccine with a defined antigen adjuvant composition would be more straightforward to seek regulatory approval including investigational new drug (IND)-enabling studies. 

AM: What experimental methods did you use in the study to gain insights into cellular relationships in the context of pneumonia? Why were these methods chosen?

JK: We used several methods including flow cytometry to look at the CD4 response, especially the Th1 and Th17 responses. We also used Elispsot assays for antigen re-stimulation. Lastly, we performed single-cell RNAseq as we felt this would be the most unbiased/objective way to phenotype the cells elicited by the vaccine. The single-cell RNAseq technology and assays were provided by 10x Genomics.

AM: Can you highlight the main findings from the study? What implications do they have for the development of vaccines for bacterial pneumonia?

JK: The study showed that inhaled vaccines that elicit both T cells and B cells can provide broader immunity than current vaccine platforms that largely focus on surface bacterial polysaccharides. Unexpectedly these cells were also resistant to calcineurin inhibition, a drug used to prevent solid organ transplant rejection which suggest that this platform may work in immunocompromised hosts. We need to test this in other larger animal models to see if this holds up. 

AM: How does this approach compare to current vaccines?

JK: This approach uses protein antigens instead of polysaccharide antigens. Moreover, this vaccine is administered mucosally and not by needle injection.   

AM: Can you tell us about your next steps and additional research you are planning to conduct in this area?

JK: Our next step is testing this vaccine in rabbits both for immunogenicity and safety. Further, Tulane is entering into a licensing agreement with a local company (MDR Therapeutics, LLC) for further development and potential commercialization of the vaccine.

AM: Anything else you’d like to add?

JK: We are excited that our work could represent a platform technology that could be used for both bacterial and viral pneumonia. In addition to not requiring needles, our strategy may be able to provide boarder protection compared to current pneumonia vaccines that only cover 13-23 serotypes of a single species. This vaccine technology can theoretically cover an entire genus or even taxa of organisms such as the Enterobacteriaceae family of bacteria for example.

Jay Kolls was speaking to Anna MacDonald, Science Writer for Technology Networks.