Targeting dendritic cells in humanized mice receiving adoptive T cells via monoclonal antibodies fused to Flu epitopes.
The targeting of vaccine antigens to antigen presenting cells (APC), such as dendritic cells (DCs), is a promising strategy for boosting vaccine immunogenicity and, in turn, protective and/or therapeutic efficacy. However, in vivo systems are needed to evaluate the potential of this approach for testing human vaccines. To this end, we examined human CD8(+) T-cell expansion to novel DC-targeting vaccines in vitro and in vivo in humanized mice. Vaccines incorporating the influenza matrix protein-1 (FluM1) antigen fused to human specific antibodies targeting different DC receptors, including DEC-205, DCIR, Dectin-1, and CD40, elicited human CD8(+) T-cell responses, as defined by the magnitude of specific CD8(+) T-cells to the targeted antigen. In vitro we observed differences in response to the different vaccines, particularly between the weakly immunogenic DEC-205-targeted and more strongly immunogenic CD40-targeted vaccines, consistent with previous studies. However, in humanized mice adoptively transferred (AT) with mature human T cells (HM-T), vaccines that performed weakly in vitro (i.e., DEC-205, DCIR, and Dectin-1) gave stronger responses in vivo, some resembling those of the strongly immunogenic CD40-targeted vaccine. These results demonstrate the utility of the humanized mouse model as a platform for studies of human vaccines.
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory, Bar Harbor, ME, United States(1).
John P
JP
Graham
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory, Bar Harbor, ME, United States(1).
Pierre
P
Authie
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory, Bar Harbor, ME, United States(1).
Chun I
CI
Yu
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States.
Sandra M
SM
Zurawski
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States.
Xiao-Hua
XH
Li
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States(1).
Florentina
F
Marches
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States.
Anne-Laure
AL
Flamar
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States.
Aditi
A
Acharya
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory, Bar Harbor, ME, United States(1); The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States(1); Vaccine Research Institute, INSERM UMR955, Equipe 16, Creteil, France.
Jacques
J
Banchereau
The Ralph Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Dallas, TX 75204, United States; The Jackson Laboratory, Bar Harbor, ME, United States(1); The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States(1). Electronic address: karolina.palucka@jax.org.
A Karolina
AK
Palucka
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007252:Influenza Vaccines / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*; D000099181:Dectin-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; D000939:Epitopes; D007252:Influenza Vaccines; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; D000099181:Dectin-1; C093569:DEC-205 receptor; C526731:Dcir protein, mouse; C488936:M1 protein, Influenza A virus
Cytotoxic T cells; Dendritic cell targeted vaccines; Human dendritic cells; Humanized mice