Listeria monocytogenes delivery of HPV-16 major capsid protein L1 induces systemic and mucosal cell-mediated CD4+ and CD8+ T-cell responses after oral immunization.
Neutralizing antibodies are thought to be required at mucosal surfaces to prevent human papillomavirus (HPV) transmission. However, the potential for cell-mediated immunity in mediating protection against HPV infection has not been well explored. We generated recombinant Listeria monocytogenes (Lm) constructs that secrete listeriolysin O (LLO) fused with overlapping N-terminal (LLO-L1(1-258)) or C-terminal (LLO-L1(238-474)) fragments of HPV type 16 major capsid protein L1 (HPV-16-L1). Oral immunization of mice with either construct induced IFN-gamma-producing CD8+ and CD4+ T cells in the spleen and in the Peyer's patches with the C-terminal construct. Oral immunization with both constructs resulted in diminished viral titers in the cervix and uterus of mice after intravaginal challenge with vaccinia virus expressing HPV-16-L1.
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Waleed
W
Mustafa
Paulo Cesar
PC
Maciag
Zhen-kun
ZK
Pan
Jessica R
JR
Weaver
Yuhong
Y
Xiao
Stuart N
SN
Isaacs
Yvonne
Y
Paterson
D000284:Administration, Oral; D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D016233:Immunotherapy, Active / Q000379:methods*; D008089:Listeria monocytogenes / Q000378:metabolism*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
D001427:Bacterial Toxins; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; C038705:hlyA protein, Listeria monocytogenes