Macrophage inflammatory protein-1alpha expression plasmid enhances DNA vaccine-induced immune responses against HSV-2

In this study, we examined the effectiveness of macrophage inflammatory protein (MIP)-1alpha cDNA as a HSV-2 DNA vaccine adjuvant. pcDNA3-gD (pgD) and pcDNA3-MIP-1alpha (pMIP-1alpha) were co-injected to examine the modulatory effects of MIP-1alpha on immune phenotype and protection against lethal challenge with HSV-2. We found that Th-cell proliferative responses were dramatically enhanced by co-injection of pgD and pMIP-1alpha compared with injection of pgD alone. The secretion of IL-2 and IFN-gamma was also significantly increased by pgD and pMIP-1alpha co-injection; however, the production of cytokines IL-4 and IL-10 was not affected by co-injection. pgD and pMIP-1alpha co-injection resulted in a moderate enhancement of systemic gD-specific antibody level, but mucosal secretory IgA was markedly enhanced. When BALB/c mice were challenged intravaginally with 100 LD50 of HSV-2 strain Sav, pMIP-1alpha co-injection with pgD improved their survival rate and significantly reduced both the number of mice with lesions and the lesion severity. Therefore, MIP-1alpha cDNA as a HSV-2 DNA vaccine adjuvant drives antigen-specific Th1-type responses, reducing HSV-2-derived morbidity and mortality.