Immunostimulatory sequence oligodeoxynucleotide: A novel mucosal adjuvant

The majority of infectious agents enter the body via mucosal surfaces. Therefore, there is great interest in developing vaccination strategies that lead to mucosal immunity. However, to generate strong mucosal immune responses to nonreplicating immunogens, mucosal delivery with an adjuvant is required, and no safe and effective mucosal adjuvants are presently available for use in humans. Recently, immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) has been shown to be a potent mucosal adjuvant. Intranasal (i.n.) delivery of antigen with ISS-ODN elicits a secretory IgA response both locally in respiratory secretions and distally in intestinal and vaginal secretions. In this regard, ISS-ODN has been shown to be as effective as cholera toxin (CT), but unlike CT, ISS-ODN has not been shown to have significant toxicity. Furthermore, i.n. antigen/ISS-ODN coimmunization induces a strong Th(1)-biased systemic immune response with cytotoxic T lymphocyte activity. These observations suggest that ISS-ODN would be an ideal mucosal adjuvant for development of vaccines against mucosal pathogens.