Transcriptomic analysis of mice vaccinated IM and IN with the BECC438b adjuvant to protect against B. pertussis challenge
Description
Expression browser data for the manuscript: "BECC438b TLR4 agonist improves responses to nasal and muscular DTaP pertussis vaccines in murine challenge models" by DeJong et al., 2022 Data was obtained from the lungs of female CD-1 mice at 3 days post B. pertussis challenge. Study abstract: With the knowledge that the protection afforded by acellular pertussis formulations is waning, there has been an effort to develop improved vaccine formulations. Options to improve the vaccines involve the inclusion of different antigens, the utilization of different adjuvants, and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination induces a localized immune response within the nasal cavity. In the case of a pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest known duration of protection. Further, current acellular formulations utilize the alum adjuvant, which is thought to play a role in the waning immune response. With this experiment, we aimed to implement a new adjuvant, BECC438b – a TLR4 agonist – into both IM and IN acellular formulations to determine its ability to protect against pertussis infection in mice. We observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea over DTaP alone for both IM and IN administration. Further, IN administration of DTaP + BECC438b induced a Th1 polarized immune response, while IN vaccination, regardless of formulation, only polarized toward a Th2 immune response, which does not afford long-term protection against pertussis. RNAseq analysis demonstrated the ability of BECC438b to activate completely different biological pathways when compared to what was seen in mice vaccinated with DTaP alone. It is of note that IN administration of DTaP + BECC438b activated a multitude of pathways associated with the immune system, data which is supported by IN vaccination having a higher total count of immunoglobulin genes. Overall, this data supports the use of the BECC438b adjuvant, with further benefits seen from IN vaccination in regard to the activation of immune pathways and the induction of immunoglobulin genes.