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Journal of Virology, December 2002, p. 12596-12602, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12596-12602.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Trachea, Lung, and Tracheobronchial Lymph Nodes Are the Major Sites Where Antigen-Presenting Cells Are Detected after Nasal Vaccination of Mice with Human Papillomavirus Type 16 Virus-Like Particles

Carole Balmelli,1,{dagger} Stéphane Demotz,2,{ddagger} Hans Acha-Orbea,2,3 Pierre De Grandi,1 and Denise Nardelli-Haefliger1*

Department of Gynecology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne,1 Institute of Biochemistry,2 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland3

Received 7 June 2002/ Accepted 18 September 2002

Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4+ T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.

* Corresponding author. Mailing address: Département de Gynécologie, c/o Institut de Microbiologie, Bugnon 44, 1011 Lausanne, Switzerland. Phone: 41 021/314 40 81. Fax: 41 021/314 40 95. E-mail: dnardell{at}hola.hospvd.ch.

{dagger} Present address: Institute of Virology and Immunoprophylaxis, 3147 Mittelhäusern, Switzerland.

{ddagger} Present address: DICTAGENE, 1066 Epalinges, Switzerland.

Journal of Virology, December 2002, p. 12596-12602, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12596-12602.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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