In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. 2008

Alexandra Trkola, and Herbert Kuster, and Peter Rusert, and Viktor von Wyl, and Christine Leemann, and Rainer Weber, and Gabriela Stiegler, and Hermann Katinger, and Beda Joos, and Huldrych F Günthard
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. alexandra.trkola@usz.ch.

The definition of plasma neutralizing antibody titers capable of controlling human immunodeficiency virus (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 contributions of these MAbs to the total neutralization activity in patient plasma. Assessment of neutralization activities for six responding patients with partial or complete control of viremia during the MAb treatment and for the eight nonresponding patients revealed a significant difference between these groups: Among responders, MAb-mediated activity exceeded the autologous neutralization response by 1 to 2 log units (median difference, 43.3-fold), while in the nonresponder group, the autologous activity prevailed (median difference, 0.63-fold). 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. The disease stage appears to have a significant impact on the quantities needed, since titers above 1:1,000 were needed to reach the same effect in chronic infection. Although our analysis is based on very small sample 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 an effect in acute compared to chronic infection, suggesting that in early disease stages, therapeutic vaccination may show promise. Equally, this raises hopes that a preventive vaccine could become effective at comparatively lower neutralizing antibody titers.

UI MeSH Term Description Entries
D007116 Immunization, Passive Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER). Convalescent Plasma Therapy,Immunoglobulin Therapy,Immunotherapy, Passive,Normal Serum Globulin Therapy,Passive Antibody Transfer,Passive Transfer of Immunity,Serotherapy,Passive Immunotherapy,Therapy, Immunoglobulin,Antibody Transfer, Passive,Passive Immunization,Therapy, Convalescent Plasma,Transfer, Passive Antibody
D009500 Neutralization Tests The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50). Neutralization Test,Test, Neutralization,Tests, Neutralization
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D013223 Statistics as Topic Works about the science and art of collecting, summarizing, and analyzing data that are subject to random variation. Area Analysis,Estimation Technics,Estimation Techniques,Indirect Estimation Technics,Indirect Estimation Techniques,Multiple Classification Analysis,Service Statistics,Statistical Study,Statistics, Service,Tables and Charts as Topic,Analyses, Area,Analyses, Multiple Classification,Area Analyses,Classification Analyses, Multiple,Classification Analysis, Multiple,Estimation Technic, Indirect,Estimation Technics, Indirect,Estimation Technique,Estimation Technique, Indirect,Estimation Techniques, Indirect,Indirect Estimation Technic,Indirect Estimation Technique,Multiple Classification Analyses,Statistical Studies,Studies, Statistical,Study, Statistical,Technic, Indirect Estimation,Technics, Estimation,Technics, Indirect Estimation,Technique, Estimation,Technique, Indirect Estimation,Techniques, Estimation,Techniques, Indirect Estimation
D014766 Viremia The presence of viruses in the blood. Viremias
D015483 HIV Antibodies Antibodies reactive with HIV ANTIGENS. AIDS Antibodies,HIV-Associated Antibodies,HTLV-III Antibodies,HTLV-III-LAV Antibodies,LAV Antibodies,Lymphadenopathy-Associated Antibodies,T-Lymphotropic Virus Type III Antibodies, Human,HIV Associated Antibodies,HTLV III Antibodies,HTLV III LAV Antibodies,Lymphadenopathy Associated Antibodies,T Lymphotropic Virus Type III Antibodies, Human,Antibodies, AIDS,Antibodies, HIV,Antibodies, HIV Associated,Antibodies, HIV-Associated,Antibodies, HTLV III,Antibodies, HTLV-III,Antibodies, HTLV-III-LAV,Antibodies, LAV,Antibodies, Lymphadenopathy Associated,Antibodies, Lymphadenopathy-Associated
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human

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