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Deptartment of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany
Conventional vaccination strategies have failed for numerous
pathogens, and the development of novel approaches to vaccine
development is a major public health priority. Killed or subunit
vaccines represent an attractive approach due to their safety, but they
suffer from low immunogenicity and generally require adjuvants. In this
study, the possibility of harnessing CD40 signaling for enhancing the
immunogenicity of killed vaccines was investigated. Intravenous
immunization of C57BL/6 mice with heat-killed Listeria
monocytogenes (HKL) induced minimal immunity, but HKL
administered together with an agonistic anti-CD40 mAb induced high
levels of both CD4+ and CD8+ T cells capable of
producing IFN-
following in vitro HKL stimulation. HKL/anti-CD40
vaccination elicited robust protection against subsequent
Listeria challenge. Approximately 1000-fold fewer
bacteria were detected in the liver and spleen of vaccinated mice, and
vaccinated mice were also able to resist a normally lethal
Listeria challenge. CD40-mediated adjuvant activity
required endogenous IL-12 at the time of vaccination, and protection
was mediated by both CD8+ and CD4+ T cells.
Thus, CD40 signaling can deliver potent adjuvant activity for
vaccination against intracellular pathogens and is particularly
effective for pathogens requiring both CD4+ and
CD8+ T cells for effective control.
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