Cellular immunogenicity of an Ad35GGRIN+ENV and MVA-CMDR prime-boost vaccine regimen. (42.3)

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Abstract Newer HIV-1 vaccine strategies use heterologous prime-boost regimens to stimulate broader immune responses. We tested 2 heterologous vectors with heterologous HIV-1 gene inserts: Ad35GRIN+Ad35ENV and MVA-CMDR. The Ad35GRIN+Ad35ENV vaccine is comprised of two vectors containing sequences from HIV-1 subtype A (GRIN=gag, rt, int and nef and ENV=env). MVA-CMDR contains genes from HIV-1 subtype CRF01_AE (gag, env and pol). Balb/c mice (5/group) were immunized according to the following schema: Group 1:MVA-CMDR-MVA-CMDR; Group 2:MVA-CMDR-Ad35GRIN+ENV; Group 3:Ad35GRIN+ENV-MVA-CMDR; Group 4:Ad35GRIN+ENV-Ad35GRIN+ENV. Immunogenicity testing was performed at 2 weeks post boost: ELISPOT, ICS (CD107a, IFNγ, TNFα and IL-2) and pentamer (H-2Kd) Gag epitope staining were used. A variety of stimuli were used to define responses to inserts and vectors. Insert-specific immune responses were detected in all groups. The best combination was Group 3. Notably, there was a shift from a focused vector response in Group 1 to an insert response in Group 3 (0.78% CD8+INFγ gag pool response and 4.24% CD8+INFγ MVA response in Group 1 vs 5.74% CD8+INFγ gag pool response and 0.61% CD8+INFγ MVA response in Group 3). The relative contributions of vector versus insert are not clear. It appears that the insert response is dominant in the heterologous vector format and that subtle differences in cross-reactive populations can be revealed using the pentamer (H-2Kd) Gag epitope staining.