Aerosol Delivery of Virus-like Particles to the Genital Tract Induces Local and Systemic Antibody Responses

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2011 May 10

PMID 21549786

Citations 9

Authors

Zoe Hunter

Ebenezer Tumban

Agnieszka Dziduszko

Bryce Chackerian

Affiliations

Soon will be listed here.

Abstract

The induction of mucosal immune responses in the genital tract may be important for increasing the effectiveness of vaccines for sexually transmitted infections (STIs). In this study, we asked whether direct immunization of the mouse genital tract with a non-replicating virus-like particle (VLP)-based vaccine could induce local mucosal as well as systemic antibody responses. Using VLPs derived from two bacteriophages, Qβ and PP7, and from a mammalian virus that normally infects the genital tract, human papillomavirus (HPV), we show that intravaginal aerosol administration of VLPs can induce high titer IgG and IgA antibodies in the female genital tract as well as IgG in the sera. Using a mouse model for HPV infection, we show that intravaginal immunization with either HPV type 16 VLPs or with PP7 bacteriophage VLPs displaying a peptide derived from the HPV minor capsid protein L2 could protect mice from genital infection with an HPV16 pseudovirus. These results provide a general method for inducing genital mucosal and systemic antibody responses using VLP-based immunogens.

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References

Storni T, Ruedl C, Schwarz K, Schwendener R, Renner W, Bachmann M . Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol. 2004; 172(3):1777-85. DOI: 10.4049/jimmunol.172.3.1777. View

Echchannaoui H, Bianchi M, Baud D, Bobst M, Stehle J, Nardelli-Haefliger D . Intravaginal immunization of mice with recombinant Salmonella enterica serovar Typhimurium expressing human papillomavirus type 16 antigens as a potential route of vaccination against cervical cancer. Infect Immun. 2008; 76(5):1940-51. PMC: 2346685. DOI: 10.1128/IAI.01484-07. View

Di Tommaso A, Saletti G, Pizza M, Rappuoli R, Dougan G, Abrignani S . Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant. Infect Immun. 1996; 64(3):974-9. PMC: 173865. DOI: 10.1128/iai.64.3.974-979.1996. View

Morrison L, Da Costa X, Knipe D . Influence of mucosal and parenteral immunization with a replication-defective mutant of HSV-2 on immune responses and protection from genital challenge. Virology. 1998; 243(1):178-87. DOI: 10.1006/viro.1998.9047. View

Vancott T, Kaminski R, Mascola J, Kalyanaraman V, Wassef N, Alving C . HIV-1 neutralizing antibodies in the genital and respiratory tracts of mice intranasally immunized with oligomeric gp160. J Immunol. 1998; 160(4):2000-12. View

Lowy D, Schiller J . Prophylactic human papillomavirus vaccines. J Clin Invest. 2006; 116(5):1167-73. PMC: 1451224. DOI: 10.1172/JCI28607. View

Bachmann M, Schwarz K, Wolint P, Meijerink E, Martin S, Manolova V . Cutting edge: distinct roles for T help and CD40/CD40 ligand in regulating differentiation of proliferation-competent memory CD8+ T cells. J Immunol. 2004; 173(4):2217-21. DOI: 10.4049/jimmunol.173.4.2217. View

Lenz P, Day P, Pang Y, FRYE S, JENSEN P, Lowy D . Papillomavirus-like particles induce acute activation of dendritic cells. J Immunol. 2001; 166(9):5346-55. DOI: 10.4049/jimmunol.166.9.5346. View

Kozlowski P, Williams S, Lynch R, Flanigan T, Patterson R, Cu-Uvin S . 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):566-74. DOI: 10.4049/jimmunol.169.1.566. View

10.

Caldeira J, Medford A, Kines R, Lino C, Schiller J, Chackerian B . Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7. Vaccine. 2010; 28(27):4384-93. PMC: 2881612. DOI: 10.1016/j.vaccine.2010.04.049. View

11.

Cuburu N, Kweon M, Hervouet C, Cha H, Pang Y, Holmgren J . Sublingual immunization with nonreplicating antigens induces antibody-forming cells and cytotoxic T cells in the female genital tract mucosa and protects against genital papillomavirus infection. J Immunol. 2009; 183(12):7851-9. PMC: 7370923. DOI: 10.4049/jimmunol.0803740. View

12.

Roberts J, Buck C, Thompson C, Kines R, Bernardo M, Choyke P . Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nat Med. 2007; 13(7):857-61. DOI: 10.1038/nm1598. View

13.

Alphs H, Gambhira R, Karanam B, Roberts J, Jagu S, Schiller J . Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2. Proc Natl Acad Sci U S A. 2008; 105(15):5850-5. PMC: 2299222. DOI: 10.1073/pnas.0800868105. View

14.

Fraillery D, Zosso N, Nardelli-Haefliger D . Rectal and vaginal immunization of mice with human papillomavirus L1 virus-like particles. Vaccine. 2009; 27(17):2326-34. DOI: 10.1016/j.vaccine.2009.02.029. View

15.

Hervouet C, Luci C, Cuburu N, Cremel M, Bekri S, Vimeux L . Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract. Vaccine. 2010; 28(34):5582-90. DOI: 10.1016/j.vaccine.2010.06.033. View

16.

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

17.

Hunter Z, Smyth H, Durfee P, Chackerian B . Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a virus-like particle based vaccine. Vaccine. 2009; 28(2):403-14. PMC: 2789199. DOI: 10.1016/j.vaccine.2009.10.035. View

18.

Chackerian B, Durfee M, Schiller J . Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol. 2008; 180(9):5816-25. PMC: 3493123. DOI: 10.4049/jimmunol.180.9.5816. View

19.

Wira C, Fahey J, Sentman C, Pioli P, Shen L . Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev. 2005; 206:306-35. DOI: 10.1111/j.0105-2896.2005.00287.x. View

20.

Plummer E, Manchester M . Viral nanoparticles and virus-like particles: platforms for contemporary vaccine design. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010; 3(2):174-196. PMC: 7169818. DOI: 10.1002/wnan.119. View