Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies
Fig 4
Resistance to one set of VRC01-class antibodies renders the viruses resistant to other antibodies in the same class.
(A) NIH45-46 passage 5 swarm was further passaged 5 times in the presence of NIH45-46 and 3BNC117 at the concentrations shown in S2A Fig. The resulting 3BNC117 passage 5 swarm was assessed for its sensitivity against the indicated antibodies. ‘Control passage 10’ is the parental library swarm passaged 10 times in total in the absence of any antibody. (B) Neutralization assays of the VRC07 passage 5 swarm using the indicated VRC01-class bNAbs. VRC07 passage 5 swarm was obtained by passaging the NIH45-46 passage 5 swarm 5 times each against 3BNC117 and VRC07. As a control (‘Control passage 15’), the parental virus library was passaged the same number of times (15) in the absence of any antibody. Statistical significance was calculated by two-way ANOVA and p value was <0.001 for each antibody. (C) Neutralizing assays of the same swarm as shown in (B) using non-VRC01 class CD4bs antibody b12 and non-CD4bs bNAbs 10–1074, 10E8 and PGDM1400. 10–1074 recognizes a V3-loop proximal glycan, 10E8 binds the gp41 MPER region, and PGDM1400 recognizes the apex of the Env oligomer. The table below the graphs shows the IC50 values of the indicated antibodies, calculated from the neutralization assays, for the control passage 15 and VRC07 passage 5 swarms. Dotted lines in (A-C) represent average IC80 values of the antibodies for ADA isolate, and were obtained from the LANL database CATNAP (http://hiv.lanl.gov/catnap). In the case of the N6 and 10–1074, only IC50 values are available: 0.074 μg/ml and 0.003 μg/ml, respectively. Averages ± SD of three independent experiments performed in duplicates are shown.