Modeling dendritic cell vaccination for influenza prophylaxis: potential applications for niche populations.

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Konduri V, Decker WK, Halpert MM, Gilbert B, Safdar A.

J Infect Dis. 2013 Jun 1;207(11):1764-72.

BACKGROUND: Cancer patients can exhibit negligible responses to prophylactic
vaccinations, including influenza vaccination. To help address this issue, we
developed in vitro and in vivo models of dendritic cell (DC) immunotherapy for
the prevention of influenza virus infection.
METHODS: Human cord blood (CB)-derived or mouse splenocyte-derived DCs were
loaded with purified recombinant hemagglutinin (rHA). T-cell responses to
HA-loaded CB-derived DCs were determined by ELISpot. Protective efficacy was
determined by vaccination of BALB/c mice with a single injection of 10(6)
autologous DCs. DC migration to peripheral lymphoid organs was verified by
carboxyfluorescein succinimidyl ester staining, and HA-specific antibody titers
were determined by enzyme-linked immunosorbent assay. Mice were then challenged
intranasally with BALB/c-adapted A/New Caledonia influenza virus derived from
four consecutive lung pool passages. Antigen-presenting cell (APC) dysfunction
was modeled using the MAFIA transgenic system, in which the Csf1r promoter
conditionally drives AP20178-inducible Fas.
RESULTS: CB-derived human DCs were able to generate de novo T-cell responses
against rHA, as determined by a system of rigorous controls. Mice vaccinated
intraperitoneally developed HA titers detectable at serum dilutions of >1:1000.
HA seroconverters survived virus challenge, whereas unvaccinated controls and
vaccinated nonseroconverters lost weight and died. Furthermore, use of a model of
APC-specific immunosuppression revealed that DC vaccination could generate
HA-specific antibody titers under conditions in which protein vaccination could
not.
CONCLUSIONS: The model demonstrates that DC immunotherapy for the prevention of
influenza is feasible, and studies are underway to determine whether populations
of immunosuppressed individuals might ultimately benefit from the procedure.