TY - JOUR
T1 - Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials
AU - Montefiori, David C.
AU - Karnasuta, Chitraporn
AU - Huang, Ying
AU - Ahmed, Hasan
AU - Gilbert, Peter
AU - De Souza, Mark S.
AU - McLinden, Robert
AU - Tovanabutra, Sodsai
AU - Laurence-Chenine, Agnes
AU - Sanders-Buell, Eric
AU - Moody, M. Anthony
AU - Bonsignori, Mattia
AU - Ochsenbauer, Christina
AU - Kappes, John
AU - Tang, Haili
AU - Greene, Kelli
AU - Gao, Hongmei
AU - Labranche, Celia C.
AU - Andrews, Charla
AU - Polonis, Victoria R.
AU - Rerks-Ngarm, Supachai
AU - Pitisuttithum, Punnee
AU - Nitayaphan, Sorachai
AU - Kaewkungwal, Jaranit
AU - Self, Steve G.
AU - Berman, Phillip W.
AU - Francis, Donald
AU - Sinangil, Faruk
AU - Lee, Carter
AU - Tartaglia, Jim
AU - Robb, Merlin L.
AU - Haynes, Barton F.
AU - Michael, Nelson L.
AU - Kim, Jerome H.
N1 - Funding Information:
Financial support. This study was supported by the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, by the Center for HIV/AIDS Vaccine Immunology (grant AI678501 from the Division of Acquired Immunodeficiency Syndrome, NIAID, NIH), and by an interagency agreement (Y1-AI-2642-12) between the US Army Medical Research and Materiel Command and the NIAID. This work was also supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense.
PY - 2012/8/1
Y1 - 2012/8/1
N2 - 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. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
AB - 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. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
UR - http://www.scopus.com/inward/record.url?scp=84863932778&partnerID=8YFLogxK
U2 - 10.1093/infdis/jis367
DO - 10.1093/infdis/jis367
M3 - Article
C2 - 22634875
AN - SCOPUS:84863932778
SN - 0022-1899
VL - 206
SP - 431
EP - 441
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -