Enhancement of protective humoral (Th2) and cell-mediated (Th1) immune responses against herpes simplex virus-2 through co-delivery of granulocyte-macrophage colony-stimulating factor expression cassettes

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Abstract
Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) could in theory attract antigen‐presenting cells in muscle following intramuscular DNA immunization, resulting in enhanced antigen‐specific immune responses. Thus, such adjuvants could constitute an important addition to a herpes vaccine by amplifying specific immune responses. Here we investigate the utility of GM‐CSF cDNA as a vaccine adjuvant for herpes simplex virus (HSV)‐2 in a mouse challenge model. GM‐CSF cDNA co‐injection enhanced levels of specific IgG, IgE and IgA against HSV‐2 gD protein significantly higher than gD plasmid vaccination alone. Moreover, GM‐CSF co‐injection induced a dramatic increase in IgG1 levels, as compared to IgG2a levels, suggesting a Th2 bias in the response. T helper cell proliferation and secretion of cytokines (IL‐2 and IFN‐γ) were significantly increased by GM‐CSF cDNA co‐injection. When challenged with a lethal dose of HSV‐2, GM‐CSF co‐injection increased survival rates to 90 %, an improvement as compared to gD vaccination alone (60 – 63 %). Furthermore, GM‐CSF cDNA co‐injection reduced herpetic lesions and resulted in a faster recovery from lesions. These data indicate that GM‐CSF cDNA enhances both humoral and cellular immune responses and enhances vaccine efficacy, resulting in reduced HSV‐2‐derived morbidity as well as mortality.