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167 Magnitude and Breadth of the Neutralizing Antibody Response in RV144

Karnasuta, Chitraporn1; McLinden, Robert2; Souza, Mark de1; Karasavva, Nicos1; Tovanabutra, Sodsai2; Laurence-Chenine, Agnes2; Sanders-Buell, Eric2; Ochsenbauer, Christina3; Kappes, John3; Polonis, Victoria2; Michael, Nelson2; Kim, Jerome2; Montefiori, David4

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 71
doi: 10.1097/01.qai.0000397354.61168.bc

1U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; 2U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, MD; 3University of Alabama at Birmingham, Birmingham, AL; and 4Duke University Medical Center, Durham, NC

RV144 is a recently completed efficacy trial in Thailand of a candidate HIV-1 Env-containing vaccine that provided modest protection against the acquisition of HIV-1 infection in subjects who were mostly at risk of heterosexually acquired infection with CRF01_AE HIV-1 (Rerks-Ngarm S, et al., N. Engl. J. Med. 361:2209-2220, 2009). We assessed the magnitude and breadth of the neutralizing antibody response in a TZM-bl assay against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of virus at two weeks post final immunization in this trial. Moderate neutralizing activity was detected against 3 of 5 tier 1 viruses (MN.3, SF162.LS, MW965.26). No positive neutralization of tier 2 CRF01_AE Env-pseudotyped viruses was detected. The overall neutralizing antibody response as assessed in TZM-bl cells was weaker than the response seen in two earlier clinical trials of protein subunit Env vaccines (Vax003, Vax004) that failed to show a measurable level of protection.

In contrast to the negative results obtained for tier 2 viruses in the TZM-bl assay, plasma samples from RV144 exhibited sporadic positive neutralizing activity against tier 2 CRF01_AE viruses when A3R5 cells (CEM human lymphoblastoid cell origin) were used as targets for infection in the assay. The A3R5 cell line also appears to be about 10-times more sensitive than TZM-bl cells for detecting neutralization by monoclonal antibodies and sera from chronically HIV-1-infected individuals. We are currently using the A3R5 assay to assess the neutralizing antibody response in Vax003 and Vax004 for direct comparison to RV144.

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