Parenteral and oral immunization with a plasmid DNA expressing the human papillomavirus 16-L1 gene induces systemic and mucosal antibodies and cytotoxic T lymphocyte responses

The association of human papillomavirus (HPV) infection and cervical cancer has been demonstrated. The development of a prophylactic vaccine to protec t against primary HPV infection may therefore be an efficient means to redu ce the incidence of this cancer worldwide. To assess the capacity of a plas mid DNA that expresses the Ll gene of HPV type 16 to induce a protective im mune response, mice were immunized by parenteral and oral routes. Animals t hat received the DNA vaccine intramuscularly, subcutaneously and orally, de veloped systemic anti-Li IgG antibodies. Antibodies developed in mice vacci nated subcutaneously were detectable twelve months post-immunization. Speci fic IgA antibodies were also found in vaginal washes from immunized mice. B oth systemic and local antibodies proved effective in a surrogate neutraliz ation assay. Splenic T cells extracted from experimental mice showed cytoto xic T lymphocytes (CTL) activity mediated by CD8 + cells. Mice were challen ged with a syngeneic melanoma cell line, engineered to express the HPV16-L1 protein, tumours in vaccinated animals showed slower growth rate, correlat ed directly with a longer survival of mice. The results suggest that the Ll -based DNA vaccine may be useful for the prevention of primary infections b y HPV16. (C) 2002 Wiley-Liss, Inc.