Potent CD4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF

DH Barouch, S Santra, K Tenner-Racz… - The Journal of …, 2002 - journals.aai.org
DH Barouch, S Santra, K Tenner-Racz, P Racz, MJ Kuroda, JE Schmitz, SS Jackson…
The Journal of Immunology, 2002journals.aai.org
Virus-specific CD4+ T cell responses have been shown to play a critical role in controlling
HIV-1 replication. Candidate HIV-1 vaccines should therefore elicit potent CD4+ as well as
CD8+ T cell responses. In this report we investigate the ability of plasmid GM-CSF to
augment CD4+ T cell responses elicited by an HIV-1 gp120 DNA vaccine in mice.
Coadministration of a plasmid expressing GM-CSF with the gp120 DNA vaccine led to only
a marginal increase in gp120-specific splenocyte CD4+ T cell responses. However …
Abstract
Virus-specific CD4+ T cell responses have been shown to play a critical role in controlling HIV-1 replication. Candidate HIV-1 vaccines should therefore elicit potent CD4+ as well as CD8+ T cell responses. In this report we investigate the ability of plasmid GM-CSF to augment CD4+ T cell responses elicited by an HIV-1 gp120 DNA vaccine in mice. Coadministration of a plasmid expressing GM-CSF with the gp120 DNA vaccine led to only a marginal increase in gp120-specific splenocyte CD4+ T cell responses. However, immunization with a bicistronic plasmid that coexpressed gp120 and GM-CSF under control of a single promoter led to a dramatic augmentation of vaccine-elicited CD4+ T cell responses, as measured by both cellular proliferation and ELISPOT assays. This augmentation of CD4+ T cell responses was selective, since vaccine-elicited Ab and CD8+ T cell responses were not significantly changed by the addition of GM-CSF. A 100-fold lower dose of the gp120/GM-CSF bicistronic DNA vaccine was required to elicit detectable gp120-specific splenocyte proliferative responses compared with the monocistronic gp120 DNA vaccine. Consistent with these findings, im injection of the gp120/GM-CSF bicistronic DNA vaccine evoked a more extensive cellular infiltrate at the site of inoculation than the monocistronic gp120 DNA vaccine. These results demonstrate that bicistronic DNA vaccines containing GM-CSF elicit remarkably potent CD4+ T cell responses and suggest that optimal Th cell priming requires the precise temporal and spatial codelivery of Ag and GM-CSF.
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