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 L1 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-L1 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 L1-based DNA vaccine may be useful for the prevention of primary infections by HPV16.
Rocha-Zavaleta
Leticia
L
Department of Molecular Biology, Institute of Biomedical Research, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. lrochaz@servidor.unam.mx
Alejandre
Jorge E
JE
Garcia-Carranca
Alejandro
A
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins; D003602:Cytotoxicity, Immunologic; D005260:Female; D006385:Hemagglutination Inhibition Tests; D018928:Immunity, Mucosal; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D010957:Plasmids / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines; C063317:L1 protein, Human papillomavirus type 16