Modeling Dendritic Cell Vaccination for Influenza Prophylaxis: Potential Applications for Niche Populations

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 b...

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Bibliographic Details
Published in:The Journal of infectious diseases 2013-06, Vol.207 (11), p.1764-1772
Main Authors: Konduri, Vanaja, Decker, William K., Halpert, Matthew M., Gilbert, Brian, Safdar, Amar
Format: Article
Language:English
Subjects:
Animals
Antibodies
Biological and medical sciences
Blood
Cancer
Cross reaction
Dendritic cells
Dendritic Cells - immunology
Disease Models, Animal
Enzyme-Linked Immunospot Assay
Fundamental and applied biological sciences. Psychology
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Humans
Immunotherapy - methods
Infectious diseases
Influenza
Influenza A virus - genetics
Influenza A virus - immunology
Influenza virus
Medical sciences
Mice
Mice, Inbred BALB C
Microbiology
Orthomyxoviridae
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Protein isoforms
Recombinant Proteins - genetics
Recombinant Proteins - immunology
T lymphocytes
T-Lymphocytes - immunology
Vaccination
VIRUSES
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jit087