tetano
Editor, Senior Moderator
J Infect Dis. 2013 Mar 4. [Epub ahead of print]
Modeling Dendritic Cell Vaccination for Influenza Prophylaxis: Potential Applications for Niche Populations.
Konduri V, Decker WK, Halpert MM, Gilbert B, Safdar A.
Source
Department of Pathology & Immunology.
Abstract
Background. Cancer patients can exhibit negligible responses to prophylactic vaccinations including influenza vaccination. Toward the goal of addressing this issue, we developed in vitro and in vivo models of dendritic cell (DC) immunotherapy for the prevention of influenza infection.Methods. Human cord blood (CB)-derived or mouse splenocyte-derived DCs were loaded with purified rHA protein. T-cell responses to HA-loaded CB DC were determined by ELISpot. Protective efficacy was determined by vaccination of Balb/c mice with a single injection of 1 x 106 autologous DCs. DC migration to peripheral lymphoid organs was verified by CFSE staining, and HA-specific antibody titers were determined by ELISA. Mice were then challenged intranasally with Balb/c-adapted A/New Caledonia influenzavirus derived from passage four lung pools. APC dysfunction was modeled using the MAFIA transgenic system in which the Csf1r promoter conditionally drives AP20178-inducible Fas.Results. CB-derived human DC were able to generate de novo T-cell responses against recombinant HA as determined by a system of rigorous controls. Mice vaccinated i.p. developed HA titers detectable at serum dilutions>1:1,000. HA seroconverters survived virus challenge whereas unvaccinated controls and vaccinated non-seroconverters lost weight and died. Further, using a model of APC-specific immunosuppression, DC vaccination could generate HA-specific antibody titers under conditions in which protein vaccination could not.Conclusions. The model demonstrates that dendritic cell 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.
PMID:
23460750
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23460750
Modeling Dendritic Cell Vaccination for Influenza Prophylaxis: Potential Applications for Niche Populations.
Konduri V, Decker WK, Halpert MM, Gilbert B, Safdar A.
Source
Department of Pathology & Immunology.
Abstract
Background. Cancer patients can exhibit negligible responses to prophylactic vaccinations including influenza vaccination. Toward the goal of addressing this issue, we developed in vitro and in vivo models of dendritic cell (DC) immunotherapy for the prevention of influenza infection.Methods. Human cord blood (CB)-derived or mouse splenocyte-derived DCs were loaded with purified rHA protein. T-cell responses to HA-loaded CB DC were determined by ELISpot. Protective efficacy was determined by vaccination of Balb/c mice with a single injection of 1 x 106 autologous DCs. DC migration to peripheral lymphoid organs was verified by CFSE staining, and HA-specific antibody titers were determined by ELISA. Mice were then challenged intranasally with Balb/c-adapted A/New Caledonia influenzavirus derived from passage four lung pools. APC dysfunction was modeled using the MAFIA transgenic system in which the Csf1r promoter conditionally drives AP20178-inducible Fas.Results. CB-derived human DC were able to generate de novo T-cell responses against recombinant HA as determined by a system of rigorous controls. Mice vaccinated i.p. developed HA titers detectable at serum dilutions>1:1,000. HA seroconverters survived virus challenge whereas unvaccinated controls and vaccinated non-seroconverters lost weight and died. Further, using a model of APC-specific immunosuppression, DC vaccination could generate HA-specific antibody titers under conditions in which protein vaccination could not.Conclusions. The model demonstrates that dendritic cell 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.
PMID:
23460750
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23460750