Generation and Characterization of a Preventive and Therapeutic HPV DNA Vaccine

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2007 Dec 22

PMID 18096279

Citations 35

Authors

Daejin Kim

Ratish Gambhira

Balasubramanyam Karanam

Archana Monie

Chien-Fu Hung

Richard Roden

T-C Wu

Affiliations

Soon will be listed here.

Abstract

Cervical cancer is one of the most common cancers in women worldwide. Persistent infection with human papillomavirus (HPV) is considered to be the etiological factor for cervical cancer. Therefore, an effective vaccine against HPV infections may lead to the control of cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infections as well as cell-mediated immunity to eliminate established infection or HPV-related disease. In the current study, we have generated a potential preventive and therapeutic HPV DNA vaccine using human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2). We found that vaccination with hCRTE6E7L2 DNA vaccine induced a potent E6/E7-specific CD8+ T cell immune response, resulting in a significant therapeutic effect against E6/E7 expressing tumor cells. In addition, vaccination with hCRTE6E7L2 DNA generated significant L2-specific neutralizing antibody responses, protecting against pseudovirion infection. Thus, the hCRTE6E7L2 DNA vaccines are capable of generating potent preventive and therapeutic effects in vaccinated mice. Our data has significant clinical implications.

Citing Articles

Treatment and Prevention of HPV-Associated Skin Tumors by HPV Vaccination.

Meyer T, Stockfleth E Vaccines (Basel). 2025; 12(12.

PMID: 39772099 PMC: 11680430. DOI: 10.3390/vaccines12121439.

Current status and future directions for the development of human papillomavirus vaccines.

Wang R, Huang H, Yu C, Li X, Wang Y, Xie L Front Immunol. 2024; 15:1362770.

PMID: 38983849 PMC: 11231394. DOI: 10.3389/fimmu.2024.1362770.

A safe and potentiated multi-type HPV L2-E7 nanoparticle vaccine with combined prophylactic and therapeutic activity.

Zhao X, Zhang Y, Trejo-Cerro O, Kaplan E, Li Z, Albertsboer F NPJ Vaccines. 2024; 9(1):119.

PMID: 38926425 PMC: 11208501. DOI: 10.1038/s41541-024-00914-z.

Prevention and Treatment of HPV-Induced Skin Tumors.

Hasche D, Akgul B Cancers (Basel). 2023; 15(6).

PMID: 36980594 PMC: 10046090. DOI: 10.3390/cancers15061709.

Control of Spontaneous HPV16 E6/E7 Expressing Oral Cancer in HLA-A2 (AAD) Transgenic Mice with Therapeutic HPV DNA Vaccine.

Tseng S, Liu L, Peng S, Kim J, Ferrall L, Hung C J Biomed Sci. 2021; 28(1):63.

PMID: 34517865 PMC: 8436567. DOI: 10.1186/s12929-021-00759-x.

References

Pastrana D, Buck C, Pang Y, Thompson C, Castle P, FitzGerald P . Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18. Virology. 2004; 321(2):205-16. DOI: 10.1016/j.virol.2003.12.027. View

Bosch F, Lorincz A, Munoz N, Meijer C, Shah K . The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002; 55(4):244-65. PMC: 1769629. DOI: 10.1136/jcp.55.4.244. View

Gao Q, Singh L, Kumar A, Srinivasan S, Wazer D, Band V . Human papillomavirus type 16 E6-induced degradation of E6TP1 correlates with its ability to immortalize human mammary epithelial cells. J Virol. 2001; 75(9):4459-66. PMC: 114197. DOI: 10.1128/JVI.75.9.4459-4466.2001. View

Trimble C, Lin C, Hung C, Pai S, Juang J, He L . Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe. Vaccine. 2003; 21(25-26):4036-42. DOI: 10.1016/s0264-410x(03)00275-5. View

Seder R, Gurunathan S . DNA vaccines--designer vaccines for the 21st century. N Engl J Med. 1999; 341(4):277-8. DOI: 10.1056/NEJM199907223410410. View

Peng S, Tomson T, Trimble C, He L, Hung C, Wu T . A combination of DNA vaccines targeting human papillomavirus type 16 E6 and E7 generates potent antitumor effects. Gene Ther. 2005; 13(3):257-65. PMC: 2174916. DOI: 10.1038/sj.gt.3302646. View

Cheng W, Hung C, Chai C, Hsu K, He L, Ling M . Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J Clin Invest. 2001; 108(5):669-78. PMC: 209378. DOI: 10.1172/JCI12346. View

Gambhira R, Jagu S, Karanam B, Gravitt P, Culp T, Christensen N . Protection of rabbits against challenge with rabbit papillomaviruses by immunization with the N terminus of human papillomavirus type 16 minor capsid antigen L2. J Virol. 2007; 81(21):11585-92. PMC: 2168774. DOI: 10.1128/JVI.01577-07. View

Walboomers J, Jacobs M, Manos M, Bosch F, Kummer J, Shah K . Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189(1):12-9. DOI: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. View

10.

Buck C, Pastrana D, Lowy D, Schiller J . Efficient intracellular assembly of papillomaviral vectors. J Virol. 2003; 78(2):751-7. PMC: 368835. DOI: 10.1128/jvi.78.2.751-757.2004. View

11.

Gurunathan S, Klinman D, Seder R . DNA vaccines: immunology, application, and optimization*. Annu Rev Immunol. 2000; 18:927-74. DOI: 10.1146/annurev.immunol.18.1.927. View

12.

Gambhira R, Gravitt P, Bossis I, Stern P, Viscidi R, Roden R . Vaccination of healthy volunteers with human papillomavirus type 16 L2E7E6 fusion protein induces serum antibody that neutralizes across papillomavirus species. Cancer Res. 2006; 66(23):11120-4. DOI: 10.1158/0008-5472.CAN-06-2560. View

13.

van der Burg S, Kwappenberg K, ONeill T, BRANDT R, Melief C, Hickling J . Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens. Vaccine. 2001; 19(27):3652-60. DOI: 10.1016/s0264-410x(01)00086-x. View

14.

Ho G, Studentsov Y, Bierman R, Burk R . Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev. 2004; 13(1):110-6. DOI: 10.1158/1055-9965.epi-03-0191. View

15.

Dalal S, Gao Q, Androphy E, Band V . Mutational analysis of human papillomavirus type 16 E6 demonstrates that p53 degradation is necessary for immortalization of mammary epithelial cells. J Virol. 1996; 70(2):683-8. PMC: 189867. DOI: 10.1128/JVI.70.2.683-688.1996. View

16.

Hung C, Cheng W, Hsu K, Chai C, He L, Ling M . Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen. Cancer Res. 2001; 61(9):3698-703. View

17.

Kim T, Lee J, Hung C, Peng S, Roden R, Wang M . Generation and characterization of DNA vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus. J Virol. 2004; 78(9):4638-45. PMC: 387705. DOI: 10.1128/jvi.78.9.4638-4645.2004. View

18.

Spee P, Neefjes J . TAP-translocated peptides specifically bind proteins in the endoplasmic reticulum, including gp96, protein disulfide isomerase and calreticulin. Eur J Immunol. 1997; 27(9):2441-9. DOI: 10.1002/eji.1830270944. View

19.

Ji H, Wang T, Chen C, Pai S, Hung C, Lin K . Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors. Hum Gene Ther. 1999; 10(17):2727-40. DOI: 10.1089/10430349950016474. View

20.

De Jong A, ONeill T, Khan A, Kwappenberg K, Chisholm S, Whittle N . Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine. Vaccine. 2002; 20(29-30):3456-64. DOI: 10.1016/s0264-410x(02)00350-x. View