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Updated: Jun 26, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Development of effective vaccines for old mice in a tumor model
David N Posnett1, Manuel E Engelhorn, Yun Lin
1Dep. of Medicine, Weill Medical College of Cornell University, New York, NY 10021, United States. dposnett@med.cornell.edu
Abstract:
Vaccines are often inefficient in old people and old mice. Few studies have focused on testing vaccines in old populations. Here we used DNA tumor antigen vaccines against melanoma and showed that old mice were not protected. Vaccines incorporating fusions of the tumor antigen with microbial adjuvant proteins OmpA (E. Coli) or Vp22 (Herpes simplex virus-1) dramatically improved protection of old mice. The mechanisms by which these adjuvant proteins act are distinct. TLR2 was not required for either OmpA or Vp22. Antigen processing and presentation were not boosted by these fusion constructs. However, fusion constructs with Vp22 gave a strong CD4 response to B16 melanoma and the OmpA response is MHC-II dependent. Both adjuvant fusion constructs stimulated CD4 and CD8 responses otherwise diminished in old mice.
Insights
DNA tumor antigen vaccines show limited efficacy in older mice. Fusing antigens with microbial adjuvant proteins OmpA or Vp22 significantly enhanced protection and immune responses in aged populations.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Vaccine efficacy is often reduced in elderly individuals and aged animal models.
- Limited research has explored vaccine strategies tailored for older populations.
- DNA tumor antigen vaccines have shown variable results in melanoma models.
Purpose of the Study:
- To evaluate the efficacy of DNA tumor antigen vaccines in aged mice.
- To investigate the potential of microbial adjuvant proteins (OmpA, Vp22) to enhance vaccine-induced protection in old mice.
- To explore the immunological mechanisms underlying adjuvant-mediated enhancement.
Main Methods:
- DNA tumor antigen vaccines were administered to old mice.
- Fusion constructs of tumor antigen with OmpA (Escherichia coli) or Vp22 (Herpes simplex virus-1) were tested.
- Immune responses, including CD4 and CD8 T cell responses, and protection against melanoma were assessed.
- Mechanisms involving Toll-like receptor 2 (TLR2) and major histocompatibility complex (MHC) class II were investigated.
Main Results:
- Unfused DNA tumor antigen vaccines failed to protect old mice against melanoma.
- Fusion constructs with OmpA and Vp22 significantly improved protection in old mice.
- Adjuvant proteins OmpA and Vp22 acted through distinct mechanisms, independent of TLR2.
- Antigen processing and presentation were not enhanced by the fusion constructs.
- Vp22 fusions induced a strong CD4 response, while OmpA fusions showed MHC-II dependency.
- Both adjuvant fusion constructs restored diminished CD4 and CD8 responses in aged mice.
Conclusions:
- Fusion of DNA tumor antigens with microbial adjuvants OmpA or Vp22 represents a promising strategy to overcome reduced vaccine efficacy in aging populations.
- These adjuvant fusion proteins enhance anti-tumor immunity in old mice through mechanisms distinct from TLR2 activation and antigen processing.
- The study highlights the potential of tailored vaccine designs to improve cancer immunotherapy outcomes in the elderly.
