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Journal of Virology, June 2005, p. 7059-7067, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7059-7067.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Systemic and Mucosal Cross-Clade Neutralizing Antibodies in BALB/c Mice Immunized with Human Immunodeficiency Virus Type 1 Clade A Virus-Like Particles Administered by Different Routes of Inoculation

L. Buonaguro,1 M. L. Visciano,1 M. L. Tornesello,1 M. Tagliamonte,1 B. Biryahwaho,2 and F. M. Buonaguro1*

Laboratory of Viral Oncology and AIDS Reference Center, Istituto Nazionale Tumori "Fondazione G. Pascale," Naples, Italy,1 ICSC-WL East African AIDS Research Centre, Uganda Virus Research Institute, Entebbe, Uganda2

Received 6 August 2004/ Accepted 7 February 2005

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model, based on virus-like particles (VLPs) expressing gp120 from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs), which shows the induction of neutralizing antibodies as well as cytotoxic T lymphocytes (CTL) in BALB/c mice by intraperitoneal (i.p.) administration. In the present study, immunization experiments based on a multiple-dose regimen have been performed with BALB/c mice to compare different routes of administration. i.p. and intranasal (i.n.), but not oral, administration induce systemic as well as mucosal (vaginal and intestinal) immunoglobulin G (IgG) and IgA responses. These immune sera exhibit >50% ex vivo neutralizing activity against both autologous and heterologous primary isolates. Furthermore, the administration of HIV-VLPAs by the i.n. immunization route induces a specific CTL activity, although at lower efficiency than the i.p. route. The HIV-VLPAs represent an efficient strategy to stimulate both arms of immunity; furthermore, the induction of specific humoral immunity at mucosal sites, which nowadays represent the main port of entry for HIV-1 infection, is of great interest. All these properties, and the possible cross-clade in vivo protection, could make these HIV-VLPAs a good candidate for a mono- and multicomponent worldwide preventive vaccine approach not restricted to high-priority regions, such as sub-Saharan countries.

* Corresponding author. Mailing address: Laboratory of Viral Oncology and AIDS Reference Center, Istituto Nazionale Tumori "Fond. G. Pascale," Via Mariano Semmola, 1, 80131 Naples, Italy. Phone: 39-081-5903.830. Fax: 39-081-5451276. E-mail: irccsvir{at}unina.it.

Journal of Virology, June 2005, p. 7059-7067, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7059-7067.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Buonaguro, L., Tornesello, M. L., Gallo, R. C., Marincola, F. M., Lewis, G. K., Buonaguro, F. M. (2009). Th2 Polarization in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus (HIV)-Infected Subjects, as Activated by HIV Virus-Like Particles. J. Virol. 83: 304-313 [Abstract] [Full Text]  
  • Buonaguro, L., Tornesello, M. L., Buonaguro, F. M. (2007). Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications. J. Virol. 81: 10209-10219 [Full Text]  
  • Skountzou, I., Quan, F.-S., Gangadhara, S., Ye, L., Vzorov, A., Selvaraj, P., Jacob, J., Compans, R. W., Kang, S.-M. (2007). Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- Macrophage Colony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles. J. Virol. 81: 1083-1094 [Abstract] [Full Text]  
  • Buonaguro, L., Tornesello, M. L., Tagliamonte, M., Gallo, R. C., Wang, L. X., Kamin-Lewis, R., Abdelwahab, S., Lewis, G. K., Buonaguro, F. M. (2006). Baculovirus-derived human immunodeficiency virus type 1 virus-like particles activate dendritic cells and induce ex vivo T-cell responses.. J. Virol. 80: 9134-9143 [Abstract] [Full Text]  


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