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A preliminary study on the immune responses of HPV16-E7 by combined intranasal immunization with lymphotoxin
Affiliations- The Second Affiliated Hospital of Nanjing Medical University,, Nanjing, China
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Abstract
Objectives: Human papillomavirus (HPV) ranks the first cause of cervical cancer. Cervical cancer has high prevalence rates
in women around the world. The HPV-E7 oncoprotein is expressed in cervical cancer and is a target of developing immunotherapies
against HPV-associated tumors. However, the antigenicity of this protein is low. Due to this reason, potent
adjuvants are required to enhance its therapeutic efficacy. This preliminary study aims to evaluate whether lymphotoxin
(LT) could act as an effective immune adjuvant for HPV infection in mice models.
Material and methods: Intranasal immunization was used to explore the effect of HPV-E7 and/or LT immune response.
After the third intranasal immunization, the titer for the HPV-E7 antibody was detected in serum and vaginal washing fluid.
Also, we assessed the expression of chemokine ligand 13 (CXCL13) and Peripheral Node Addressin (PNAd) in the lymph
nodes after intranasal immunization with immunohistochemical analysis.
Results: compared to HPV-E7 immunization, intranasal immunization with HPV-E7 plus LT significantly increased HPV-E7-specific
serum IgG and vaginal IgA titers. Furthermore, the combined use of HPV-E7 and LT strongly induced E7-specific CTL
responses.
Conclusions: LT can be effective for intranasal immunized HPV-E7 to improve E7-specific immune responses to HPV infection.
It is new approach to eradicate chronic HPV infection capable of inducing an effective anti-infection method.
Abstract
Objectives: Human papillomavirus (HPV) ranks the first cause of cervical cancer. Cervical cancer has high prevalence rates
in women around the world. The HPV-E7 oncoprotein is expressed in cervical cancer and is a target of developing immunotherapies
against HPV-associated tumors. However, the antigenicity of this protein is low. Due to this reason, potent
adjuvants are required to enhance its therapeutic efficacy. This preliminary study aims to evaluate whether lymphotoxin
(LT) could act as an effective immune adjuvant for HPV infection in mice models.
Material and methods: Intranasal immunization was used to explore the effect of HPV-E7 and/or LT immune response.
After the third intranasal immunization, the titer for the HPV-E7 antibody was detected in serum and vaginal washing fluid.
Also, we assessed the expression of chemokine ligand 13 (CXCL13) and Peripheral Node Addressin (PNAd) in the lymph
nodes after intranasal immunization with immunohistochemical analysis.
Results: compared to HPV-E7 immunization, intranasal immunization with HPV-E7 plus LT significantly increased HPV-E7-specific
serum IgG and vaginal IgA titers. Furthermore, the combined use of HPV-E7 and LT strongly induced E7-specific CTL
responses.
Conclusions: LT can be effective for intranasal immunized HPV-E7 to improve E7-specific immune responses to HPV infection.
It is new approach to eradicate chronic HPV infection capable of inducing an effective anti-infection method.
Keywords
human papillomavirus; HPV-E7; lymphotoxin; intranasal immunization; immunotherapy; lymphocyte homing
About this articleTitle
A preliminary study on the immune responses of HPV16-E7 by combined intranasal immunization with lymphotoxin
Journal
Issue
Article type
Research paper
Pages
301-307
Published online
2020-06-30
Page views
860
Article views/downloads
864
DOI
Pubmed
Bibliographic record
Ginekol Pol 2020;91(6):301-307.
Keywords
human papillomavirus
HPV-E7
lymphotoxin
intranasal immunization
immunotherapy
lymphocyte homing
Authors
Ya-Hong Liu
Hai-Lin Chen
Bo-Qun Xu
Kuang Wei
Xiao-Yan Ying
References (26)- Cohen P, Jhingran A, Oaknin A, et al. Cervical cancer. The Lancet. 2019; 393(10167): 169–182.
- World Health Organization (WHO). Human Papillomavirus and Related Cancers. SummaryReport Update. 2010.
- de Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol. 2018; 47: 2–13.
- Li Y, Xu C. Human Papillomavirus-Related Cancers. Adv Exp Med Biol. 2017; 1018: 23–34.
- Banister CE, Liu C, Pirisi L, et al. Identification and characterization of HPV-independent cervical cancers. Oncotarget. 2017; 8(8): 13375–13386.
- Mittal S, Banks L. Molecular mechanisms underlying human papillomavirus E6 and E7 oncoprotein-induced cell transformation. Mutat Res Rev Mutat Res. 2017; 772: 23–35.
- Dorta-Estremera S, Chin RL, Sierra G, et al. Mucosal HPV E6/E7 Peptide Vaccination in Combination with Immune Checkpoint Modulation Induces Regression of HPV Oral Cancers. Cancer Res. 2018; 78(18): 5327–5339.
- Yang Y, Che Y, Zhao Y, et al. Prevention and treatment of cervical cancer by a single administration of human papillomavirus peptide vaccine with CpG oligodeoxynucleotides as an adjuvant in vivo. Int Immunopharmacol. 2019; 69: 279–288.
- Einstein MH, Schiller JT, Viscidi RP, et al. Clinician's guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis. 2009; 9(6): 347–356.
- Upadhyay V, Fu YX. Lymphotoxin signalling in immune homeostasis and the control of microorganisms. Nat Rev Immunol. 2013; 13(4): 270–279.
- Kozlowski PA, Williams SB, Lynch RM, et al. Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle. J Immunol. 2002; 169(1): 566–574.
- Johansson EL, Wassén L, Holmgren J, et al. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect Immun. 2001; 69(12): 7481–7486.
- Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69–90.
- van der Burg SH, Melief CJM. Therapeutic vaccination against human papilloma virus induced malignancies. Curr Opin Immunol. 2011; 23(2): 252–257.
- Eberl G. A new vision of immunity: homeostasis of the superorganism. Mucosal Immunol. 2010; 3(5): 450–460.
- Gardella B, Iacobone AD, Musacchi V, et al. The Mucosal Innate Immune Response in Primary Human Papillomavirus Infection: A Pilot Study. J Low Genit Tract Dis. 2016; 20(4): 338–342.
- Yuki Y, Kiyono H. New generation of mucosal adjuvants for the induction of protective immunity. Rev Med Virol. 2003; 13(5): 293–310.
- Longet S, Lundahl MLE, Lavelle EdC. Targeted Strategies for Mucosal Vaccination. Bioconjug Chem. 2018; 29(3): 613–623.
- Bernocchi B, Carpentier R, Betbeder D. Nasal nanovaccines. Int J Pharm. 2017; 530(1-2): 128–138.
- Nardelli-Haefliger D, Lurati F, Wirthner D, et al. Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine. Vaccine. 2005; 23(28): 3634–3641.
- Koroleva EP, Fu YX, Tumanov AV. Lymphotoxin in physiology of lymphoid tissues - Implication for antiviral defense. Cytokine. 2018; 101: 39–47.
- Ying X, Chan K, Shenoy P, et al. Lymphotoxin Plays a Crucial Role in the Development and Function of Nasal-Associated Lymphoid Tissue through Regulation of Chemokines and Peripheral Node Addressin. Am J Pathol. 2005; 166(1): 135–146.
- Liu F, Kozlovskaya V, Zavgorodnya O, et al. Encapsulation of anticancer drug by hydrogen-bonded multilayers of tannic acid. Soft Matter. 2014; 10(46): 9237–9247.
- Kozlovskaya V, Xue B, Lei W, et al. Hydrogen-bonded multilayers of tannic acid as mediators of T-cell immunity. Adv Healthc Mater. 2015; 4(5): 686–694.
- Rosen SD. Ligands for L-selectin: homing, inflammation, and beyond. Annu Rev Immunol. 2004; 22: 129–156.
- Hemmerich S, Butcher EC, Rosen SD. Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody. J Exp Med. 1994; 180(6): 2219–2226.
