Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials

被引：242

作者：

Montefiori, David C. ^{[1
]}

Karnasuta, Chitraporn ^{[2
]}

Huang, Ying ^{[3
]}

Ahmed, Hasan ^{[3
]}

Gilbert, Peter ^{[3
]}

de Souza, Mark S. ^{[2
]}

McLinden, Robert ^{[4
]}

Tovanabutra, Sodsai ^{[4
]}

Laurence-Chenine, Agnes ^{[4
]}

Sanders-Buell, Eric ^{[4
]}

Moody, M. Anthony

Bonsignori, Mattia

Ochsenbauer, Christina ^{[5
]}

Kappes, John ^{[5
]}

Tang, Haili

Greene, Kelli

Gao, Hongmei

LaBranche, Celia C.

Andrews, Charla ^{[4
]}

Polonis, Victoria R. ^{[4
]}

Rerks-Ngarm, Supachai ^{[6
]}

Pitisuttithum, Punnee ^{[7
]}

Nitayaphan, Sorachai ^{[2
]}

Kaewkungwal, Jaranit ^{[7
]}

Self, Steve G. ^{[3
]}

Berman, Phillip W. ^{[8
]}

Francis, Donald ^{[9
]}

Sinangil, Faruk ^{[9
]}

Lee, Carter ^{[9
]}

Tartaglia, Jim ^{[10
]}

Robb, Merlin L. ^{[4
]}

Haynes, Barton F.

Michael, Nelson L. ^{[4
]}

Kim, Jerome H. ^{[4
]}

机构：

[1] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[2] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand

[3] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[4] Walter Reed Army Inst Res, US Mil HIV Res Program, Rockville, MD USA

[5] Univ Alabama Birmingham, Birmingham, AL USA

[6] Minist Publ Hlth, Dept Dis Control, Bangkok, Thailand

[7] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand

[8] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA

[9] Global Solut Infect Dis, San Francisco, CA USA

[10] Sanofi Pasteur, Toronto, ON, Canada

来源：

JOURNAL OF INFECTIOUS DISEASES | 2012年 / 206卷 / 03期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; CHIMERIC VIRUS; DOUBLE-BLIND; SUBTYPE-B; INFECTION; PROTECTION; THAILAND; PHASE-3; BINDING;

D O I：

10.1093/infdis/jis367

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials. Methods. Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells. Results. Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120. vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells. Conclusion. The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.

引用

页码：431 / 441

页数：11

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