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 protect against primary HPV infection may therefore be an efficient means to reduce the incidence of this cancer worldwide. To assess the capacity of a plasmid DNA that expresses the Ll gene of HPV type 16 to induce a protective immune response, mice were immunized by parenteral and oral routes. Animals that received the DNA vaccine intramuscularly, subcutaneously and orally, developed systemic anti-Li IgG antibodies. Antibodies developed in mice vaccinated subcutaneously were detectable twelve months post-immunization. Specific IgA antibodies were also found in vaginal washes from immunized mice. Both systemic and local antibodies proved effective in a surrogate neutralization assay. Splenic T cells extracted from experimental mice showed cytotoxic T lymphocytes (CTL) activity mediated by CD8 + cells. Mice were challenged with a syngeneic melanoma cell line, engineered to express the HPV16-L1 protein, tumours in vaccinated animals showed slower growth rate, correlated 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 by HPV16. (C) 2002 Wiley-Liss, Inc.