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.
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-VLP(A)s), 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-VLP(A)s by the i.n. immunization route induces a specific CTL activity, although at lower efficiency than the i.p. route. The HIV-VLP(A)s 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-VLP(A)s a good candidate for a mono- and multicomponent worldwide preventive vaccine approach not restricted to high-priority regions, such as sub-Saharan countries.
Buonaguro
L
L
Laboratory of Viral Oncology and AIDS Reference Center, Istituto Nazionale Tumori Fond. G. Pascale, Via Mariano Semmola, 1, 80131 Naples, Italy.
Visciano
M L
ML
Tornesello
M L
ML
Tagliamonte
M
M
Biryahwaho
B
B
Buonaguro
F M
FM
D016915:AIDS Vaccines / Q000008:administration & dosage; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000939:Epitopes; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015488:HIV Antigens; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014454:Uganda; D014621:Vagina / Q000276:immunology; D014771:Virion / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens