Biology subjects

Boehm, D. T.

Publications and source records attributed to Boehm, D. T..

3 recordsLinked to original sources

bioRxiv2024

Intratumoral administration of mRNA-1273 vaccine delays melanoma growth in mice

BackgroundImmunotherapies are advantageous for treating cancers; however, their efficacy is limited in unresponsive hosts with "cold" tumor microenvironments. This limitation primarily stems from the lack of infiltrating CD8+ T cells, which are major effectors of the anti-cancer immune response. Here, we demonstrate the effects of intratumoral (IT) injections of the COVID-19 mRNA vaccine on the impairment of tumor growth in mice. MethodsEstablished B16F10 subcutaneous tumor models in wild type mice were used to evaluate the tumor response from IT administration of mRNA-1273. We compared treatment outcomes, immune composition, and transcriptomic effects from mRNA-1273 using survival studies, intravital imaging, flow cytometry, single-cell RNA sequencing, and abscopal studies. The ability of mRNA-1273 to enhance immune checkpoint therapy response was also evaluated. ResultsTumor growth and survival studies following a single IT injection of the COVID-19 mRNA-1273 vaccine showed significant tumor suppression and prolonged survival in tumor-bearing mice. mRNA-1273 treatment resulted in a significant increase in CD8+ T cell infiltration into the tumor microenvironment, as observed using intravital imaging and flow cytometry. Further tumor growth suppression was achieved using additional mRNA-1273 treatments. Combination administration of mRNA-1273 with immune checkpoint therapies demonstrated enhanced effects, further delaying tumor growth and improving the survival time of tumor-bearing mice. ConclusionIT injection of mRNA-1273 significantly reduced tumor growth and enhanced CD8+ T cells in the tumor microenvironment. Tumor suppression was further enhanced following multiple injections of mRNA-1273 or when combined with immune checkpoint therapies. This study demonstrates that mRNA vaccines may be used as adjuvants for immunotherapies. What is already known on this topicO_LIMost cancer patients develop adequate antibody response to vaccination with mRNA-1273 and produce spike-specific T cell responses. However, it is unclear if the mRNA-1273 vaccine can be used to elicit anti-tumor T cell responses. C_LI What this study addsO_LIIntratumoral injection of mRNA-1273 significantly delayed melanoma growth. C_LIO_LITreatment with mRNA-1273 significantly increased CD8+ T cell infiltration into the tumor microenvironment. C_LIO_LIEnhanced effects of combination mRNA-1273 and immune checkpoint therapy in anti-tumor immunity. C_LI How this study might affect research, practice, or policyO_LImRNA vaccine may be an effective adjuvant with immune checkpoint therapy. C_LI

immunology↗

bioRxiv2023

Addition of adjuvant to DTaP modulates vaccine-induced immunological responses but is insufficient to improve protection in CD-1 mice

3.1Pertussis is a vaccine-preventable respiratory disease caused by the Gram-negative bacterium Bordetella pertussis. While vaccination rates remain high in developed countries, incidence of pertussis has increased following the transition from wP vaccines to aP vaccines. The reemergence of pertussis is attributed, in part, to waning immunity induced by aP vaccination. Therefore, the objective of this work was to determine if addition of adjuvant to DTaP can modulate the immune response and improve protection compared to DTaP alone. In this study we immunized outbred, female CD-1 mice with 1/320th the human dose of vehicle control, DTaP, and DTaP supplemented with adjuvant. Markers of early vaccine-induced memory were measured using a chemokine assay or by flow cytometry. Protection was assessed by measuring serological responses and quantifying bacterial burden in the respiratory tract at day 3 post-challenge. From this work we identified a partially protective aP vaccine dose to use for vaccination and challenge studies. We observed that MPLA and SWE promote robust anti-B. pertussis antibody responses and stimulate significant increases in early markers of vaccine-induced memory such as CXCL13, FDCs, and TFH cells. Quil-A induced Th1 responses compared to DTaP alone, but none of the adjuvants improved protection against challenge with B. pertussis. Overall, the data suggests that addition of adjuvant modulates the protective immune responses induced by aPs. Further studies are needed to evaluate the B cell compartment and longevity of protection.

immunology↗

bioRxiv2019

Characterizing the innate and adaptive responses of immunized mice to Bordetella pertussis infection using in vivo imaging and transcriptomic analysis

Bordetella pertussis (B. pertussis) is the causative agent of pertussis (whooping cough). Since the 1990s, pertussis has re-emerged in the United States despite an estimated 95% vaccine coverage. Our goal was to characterize neutrophil responses and gene expression profiles of murine lungs in the context of vaccination and B. pertussis challenge. We utilized a bioluminescent neutrophil mouse model (NECre luc) to track neutrophil recruitment. NECre luc mice were immunized with whole cell vaccine (WCV), acellular vaccine (ACV), or a truncated adenylate cyclase toxoid (RTX) vaccine. Neutrophil recruitment was measured in live mice across time and corroborated by flow cytometry and other data. WCV immunized mice showed signs of neutrophilia in response to B. pertussis challenge. Mice immunized with either ACV or WCV cleared the challenge infection; however immunization with RTX alone was not protective. RNA sequencing revealed distinctive gene expression profiles for each immunization group. We observed an increase in expression of genes associated with responses to infection, and changes in expression of distinct genes in each vaccine group, providing a complex view of the immune response to B. pertussis infection in mice. This study suggests that combination of immunological analysis with transcriptomic profiling can facilitate discovery of pre-clinical correlates of protection for vaccine development.

immunology↗