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J. Virol. doi:10.1128/JVI.01792-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In vivo efficacy of HIV neutralizing antibodies: Estimates for protective titers

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland, Polymun Scientific, Vienna, Austria

^* To whom correspondence should be addressed. Email: alexandra.trkola{at}usz.ch.

	Abstract

Definition of plasma neutralizing antibody titers capable of controlling HIV infection in vivo is considered a critical step in vaccine development. Here we provide estimates for effective neutralization titers by assessing samples from a recent passive immunization trial with the neutralizing monoclonal antibodies (MAbs) 2G12, 2F5 and 4E10 using an analytic strategy that dissects the contribution of these MAbs to the total neutralization activity in patient plasma. Assessment of neutralization activity in 6 responding patients with partial or complete control of viremia during the MAb treatment and the 8 non-responding patients, revealed a significant difference in these groups: Amongst responders MAb mediated activity exceeded the autologous neutralization response by 1-2 logs (median-fold difference 43.3) while in the non-responder group the autologous activity prevailed (median-fold difference 0.63). In order to reach a 50% proportion of the responders in our study cohort, MAb neutralizing titers higher than 1:200 were required based on this analysis. Disease stage appears to have a significant input on the quantities needed as titers above 1:1000 were needed to reach the same effect in chronic infection.

Although our analysis is based on very small samples numbers and thus cannot be conclusive, our data provide a first estimate on how in vitro measured neutralizing antibody activity can relate to in vivo efficacy in controlling HIV infection and may therefore provide valuable information for vaccine development. Interestingly, lower neutralizing antibody levels showed effect in acute compared to chronic infection suggesting that in early disease stages therapeutic vaccination may show promise. Equally this raises hopes that preventive vaccine could become effective at comparatively lower neutralizing antibody titers.

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