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Concurrent vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose

Studies comparing two or more vaccine platforms have historically evaluated each platform based on its ability to induce an immune response and may conclude that one vaccine is more efficacious than the other(s), leading to a recommendation for development of the more effective vaccine for clinical studies. Alternatively, these studies have documented the advantages of a diversified prime and boost regimen due to amplification of the antigen-specific T-cell population. We hypothesize here that two vaccine platforms targeting the same antigen might induce shared and distinct antigen-specific T-cell populations, and examined the possibility that two distinct vaccines could be used concomitantly.

Experimental design

Using recombinant poxvirus and yeast vaccines, we compared the T-cell populations induced by these two platforms in terms of serum cytokine response, T-cell gene expression, T-cell receptor phenotype, antigen-specific cytokine expression, T-cell avidity, and T-cell antigen-specific tumor cell lysis.

Results

These studies demonstrate for the first time that vaccination with a recombinant poxvirus platform (rV/F-CEA/TRICOM) or a heat-killed yeast vaccine platform (yeast-CEA) elicits T-cell populations with both shared and unique phenotypic and functional characteristics. Furthermore, both the antigen and the vector play a role in the induction of distinct T-cell populations.

Conclusions

In this study, we demonstrate that concurrent administration of two vaccines targeting the same antigen induces a more diverse T-cell population that leads to enhanced antitumor efficacy. These studies provide the rationale for future clinical studies investigating concurrent administration of vaccine platforms targeting a single antigen to enhance the antigen-specific immune response.

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Acknowledgments

The authors acknowledge the excellent technical assistance of Marion Taylor and Anais Kasten-Sportes, and the editorial assistance of Bonnie L. Casey in the preparation of this manuscript.

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, MSC 1750, Bethesda, MD, 20892, USA

    Amanda L. Boehm, Jack Higgins, Jeffrey Schlom & James W. Hodge

  2. GlobeImmune, Inc., 1450 Infinite Dr., Louisville, CO, 80027, USA

    Alex Franzusoff

Authors
  1. Amanda L. Boehm
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  2. Jack Higgins
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  3. Alex Franzusoff
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  4. Jeffrey Schlom
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  5. James W. Hodge
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Corresponding author

Correspondence to Jeffrey Schlom.

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Boehm, A.L., Higgins, J., Franzusoff, A. et al. Concurrent vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations. Cancer Immunol Immunother 59, 397–408 (2010). https://doi.org/10.1007/s00262-009-0759-7

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  • DOI: https://doi.org/10.1007/s00262-009-0759-7

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