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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3730-3736
Immunostimulatory CpG Oligodeoxynucleotides Enhance the Immune
Response to Vaccine Strategies Involving Granulocyte-Macrophage
Colony-Stimulating Factor
Hsin-Ming Liu,
Sally E. Newbrough,
Sudershan K. Bhatia,
Christopher E. Dahle,
Arthur M. Krieg, and
George J. Weiner
From the University of Iowa Interdisciplinary Graduate Program in
Immunology, University of Iowa Department of Internal Medicine,
University of Iowa Cancer Center, and Iowa City Veterans Affairs
Medical Center, Iowa City, IA.
Immunostimulatory oligodeoxynucleotides containing the CpG motif
(CpG ODN) can activate various immune cell subsets and induce production of a number of cytokines. Prior studies have demonstrated that both CpG ODN and granulocyte-macrophage colony-stimulating factor
(GM-CSF) can serve as potent vaccine adjuvants. We used the 38C13
murine lymphoma system to evaluate the immune response to a combination
of these two adjuvants. Immunization using antigen, CpG ODN, and
soluble GM-CSF enhanced production of antigen-specific antibody and
shifted production towards the IgG2a isotype, suggesting an enhanced
TH1 response. This effect was most pronounced after repeat
immunizations with CpG ODN and antigen/GM-CSF fusion protein. A single
immunization with CpG ODN and antigen/GM-CSF fusion protein 3 days
before tumor inoculation prevented tumor growth. CpG ODN enhanced the
production of interleukin-12 by bone marrow-derived dendritic cells and
increased expression of major histocompatibility complex
class I and class II molecules, particularly when cells were pulsed
with antigen/GM-CSF fusion protein. We conclude that the use of CpG ODN
in combination with strategies involving GM-CSF enhances the immune
response to antigen and shifts the response towards a TH1 response and
that this approach deserves further evaluation in tumor immunization
approaches and other conditions in which an antigen-specific TH1
response is desirable.
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