Bacterial infections present the body with multiple triggers that induce innate immune responses. As a result, using multiple adjuvants in conjugate vaccines has proven more effective at establishing long-lasting immune memory against bacterial disease.
Developing Conjugate Vaccines
As part of their research to develop improved conjugate vaccines, Dr. Luc Teyton, Professor of Immunology and Microbiology at Scripps Research Institute, and his team are studying an experimental Streptococcus pneumoniae vaccine in which RNA adjuvants are housed in a Qβ bacteriophage.
In their recent paper published in The Journal of Immunology, the researchers wanted to understand how the adjuvants in this vaccine contributed to immune responses.
To do this, they used Toll-like receptor 7 (TLR7) and natural killer T (NKT) cell knockout mice (KO), as well as double knockout (dKO) mice to observe how each adjuvant contributed to the immune response. However, when these mice were examined over time for up to one year, the research team made an unexpected finding.
A Surprising Element of Qβ Bacteriophage
Rather than seeing decreased immune activity in KO mice, Dr. Teyton and his team found that each KO mouse line had high antibody titer responses comparable to wild-type (WT) mice. In addition, the dKO mice also showed antibody responses similar to those of WT and single KO mice six to 12 months after immunization. This led the researchers to conclude that the Qβ bacteriophage used in the vaccine had its own adjuvant properties capable of triggering an innate immune response.
Through further investigation, they observed that Qβ itself triggered responses from the leading to production of the cytokines signaling proteins IFNγ, IL-1α, and IL-6. This makes Qβ different from other nanoparticles, which typically rely on the cytokine IL-1β to drive their adjuvant effect. “These findings suggest the existence of an adjuvant pathway triggered by immune recognition of a phage itself which contributes to the establishment of immune memory. This is very exciting as it could be a platform to develop vaccines against emerging antibiotic-resistant microorganisms,” shared Dr. Teyton.
Unraveling the Mystery
To understand how the dKO mice achieved antibody titers similar to those of WT mice, the research team began studying germinal center formation. While they saw diminished germinal center formation in KO mice, as expected, they did not see significant differences in antigen uptake, processing, or presentation. One difference they did identify was that after a booster dose, one year after initial vaccination, memory B cells were predominant in WT mice, but long-lived plasma cells were present in greater numbers in single and double KO mice. This led the team to conclude that long-lived plasma cells likely played a role in the persistence of antigen-specific B cell responses in KO mice.
The researchers plan to build on these findings by investigating the signaling pathways that lead to innate responses to the bacteriophage, and are excited to see how Qβ as a new adjuvant could expand vaccine possibilities in humans.
