Induction of neutralizing antibodies and cytotoxic T lymphocytes in Balb/c mice immunized with virus-like particles presenting a gp120 molecule from a HIV-1 isolate of clade A

被引:64
作者
Buonaguro, L
Racioppi, L
Tornesello, ML
Arra, C
Visciano, ML
Biryahwaho, B
Sempala, SDK
Giraldo, G
Buonaguro, FM
机构
[1] Ist Naz Tumori Fond G Pascale, Div Viral Oncol, I-80131 Naples, Italy
[2] Ist Naz Tumori Fond G Pascale, AIDS Reference Ctr, I-80131 Naples, Italy
[3] Univ Naples, Dept Cellular & Mol Biol & Pathol, Naples, Italy
[4] Ist Naz Tumori Fond G Pascale, Div Anim Facil, Naples, Italy
[5] Uganda Virus Res Inst, WL E African AIDS Res Ctr, ICSC, Entebbe, Uganda
基金
英国医学研究理事会;
关键词
vaccine; HIV-1; clade A; virus-like particles;
D O I
10.1016/S0166-3542(02)00004-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have recently developed a candidate HIV-1 vaccine based on virus-like particles (VLPs) expressing a gp120 from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). In vivo immunogenicity experiments were performed in Balb/c mice, with an immunization schedule based on a multiple-dose regimen of HIV-VLP(A)s without adjuvants, showing a significant induction of both humoral and cellular immunity. The Env-specific cellular response was investigated in vitro, scoring for both the proliferative response of T helper cells and the cytolytic activity of cytotoxic T lymphocytes (CTLs). Furthermore, immune sera showed > 50% neutralization activity against both the autologous field isolate and the heterologous T cell adapted B-clade HIV-1(IIIB) viral strain. This is one of the first examples of HIV-1 vaccines based on antigens derived from the A clade, which represents > 25% of all isolates identified world wide. In particular, the A clade is predominant in sub-Saharan countries, where 70% of the global HIV-1 infections occur, and where vaccination is the only rational strategy for an affordable prevention against HIV-1 infection. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:189 / 201
页数:13
相关论文
共 61 条
[31]   Expression and self-assembly of empty virus-like particles of hepatitis E virus [J].
Li, TC ;
Yamakawa, Y ;
Suzuki, K ;
Tatsumi, M ;
Razak, MAA ;
Uchida, T ;
Takeda, N ;
Miyamura, T .
JOURNAL OF VIROLOGY, 1997, 71 (10) :7207-7213
[32]   Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies [J].
Mascola, JR ;
Lewis, MG ;
Stiegler, G ;
Harris, D ;
VanCott, TC ;
Hayes, D ;
Louder, MK ;
Brown, CR ;
Sapan, CV ;
Frankel, SS ;
Lu, YC ;
Robb, ML ;
Katinger, H ;
Birx, DL .
JOURNAL OF VIROLOGY, 1999, 73 (05) :4009-4018
[33]  
McCutchan FE, 2000, AIDS, V14, pS31
[34]   Expression and immunogenicity of human immunodeficiency virus type 1 Gag expressed by a replication-competent rhabdovirus-based vaccine vector [J].
McGettigan, JP ;
Sarma, S ;
Orenstein, JM ;
Pomerantz, RJ ;
Schnell, MJ .
JOURNAL OF VIROLOGY, 2001, 75 (18) :8724-8732
[35]  
MONEFIORI DC, 2001, J VIROL, V75, P5879
[36]   Evidence that antibody-mediated neutralization of human immunodeficiency virus type 1 by sera from infected individuals is independent of coreceptor usage [J].
Montefiori, DC ;
Collman, RG ;
Fouts, TR ;
Zhou, JY ;
Bilska, M ;
Hoxie, JA ;
Moore, JP ;
Bolognesi, DP .
JOURNAL OF VIROLOGY, 1998, 72 (03) :1886-1893
[37]   Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors [J].
Montefiori, DC ;
Pantaleo, G ;
Fink, LM ;
Zhou, JT ;
Zhou, JY ;
Bilska, M ;
Miralles, GD ;
Fauci, AS .
JOURNAL OF INFECTIOUS DISEASES, 1996, 173 (01) :60-67
[38]   Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals [J].
Moog, C ;
Fleury, HJA ;
Pellegrin, I ;
Kirn, A ;
Aubertin, AM .
JOURNAL OF VIROLOGY, 1997, 71 (05) :3734-3741
[39]   Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection [J].
Musey, L ;
Hughes, J ;
Schacker, T ;
Shea, T ;
Corey, L ;
McElrath, MJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (18) :1267-1274
[40]   HIV-1 GAG-SPECIFIC CYTO-TOXIC LYMPHOCYTES-T DEFINED WITH RECOMBINANT VACCINIA VIRUS AND SYNTHETIC PEPTIDES [J].
NIXON, DF ;
TOWNSEND, ARM ;
ELVIN, JG ;
RIZZA, CR ;
GALLWEY, J ;
MCMICHAEL, AJ .
NATURE, 1988, 336 (6198) :484-487