Companion to Cracking the Glycan Shield

Coverage Explorer.

Switch antibodies on and off and watch how many of 525 real viruses the set still reaches (524 when 10E8 is in the set). Each square is one virus; hollow squares are the ones nothing in your selection neutralizes.

525 real viruses7 antibodies127 combinations checked← Back to the main report

VRC01 rule

Would the project recommend this set?

The project’s standing selection rule never surfaces a VRC01-containing combination when a VRC01-free one reaches equal or better coverage on the same 525 viruses. VRC01 underperformed in the AMP prevention trials because most circulating viruses were not sensitive to it^1,2. The rule checks seven combinations, and 10E8 is not part of it. This panel applies the same rule to whatever you select, comparing against every VRC01-free set with no more antibodies than yours.

Method

How these numbers were made

Viruses: the 525 viruses in the LANL CATNAP download that have at least one neutralization record against all six original antibodies^3,4,5,6,7. Records are from the LANL CATNAP database⁸. Clade C is 301 of them and clade B is 96, so the panel is not a global sample.
10E8: a seventh antibody that targets the membrane-proximal external region (MPER) of gp41⁹. It was tested on 524 of the 525 viruses. Any set that includes 10E8 is scored out of 524, and the one untested virus is shown as not covered by 10E8. 10E8 is sensitive for 372 of the 524 (71.0%). It is not one of the six antibodies in the project’s original analysis.
Sensitive: a virus counts as covered by an antibody if any of its records gives IC50 at or below 1 µg/mL, including left-censored values such as <0.05. Records such as >0.5 say nothing about the 1 µg/mL threshold and are ignored. This is the project’s corrected-censoring rule, and it reproduces the project’s counts exactly: 330, 349, 323, 294, 275, and 332 for the six antibodies, and 502 for the standing four-antibody pick. The 10E8 result uses the same rule.
Combinations: a set covers a virus if any member does (OR logic). This does not model synergy or the lower potency of an antibody mixed at fixed dose, and it says nothing about escape or resistance in a person.

References

Sources

1.Corey L, et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N Engl J Med 2021;384:1003–1014. doi:10.1056/NEJMoa2031738
2.Mkhize NN, et al. Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. PLoS Pathog 2023;19:e1011469. doi:10.1371/journal.ppat.1011469
3.Wu X, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 (VRC01). Science 2010;329:856–861. doi:10.1126/science.1187659
4.Scheid JF, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding (3BNC117). Science 2011;333:1633–1637. doi:10.1126/science.1207227
5.Mouquet H, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies (10-1074). Proc Natl Acad Sci U S A 2012;109:E3268–E3277. doi:10.1073/pnas.1217207109
6.Walker LM, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies (PGT121, PGT122, PGT128). Nature 2011;477:466–470. doi:10.1038/nature10373
7.Sok D, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex (PGDM1400). Proc Natl Acad Sci U S A 2014;111:17624–17629. doi:10.1073/pnas.1415789111
8.Yoon H, et al. CATNAP: a tool to compile, analyze and tally neutralizing antibody panels. Nucleic Acids Res 2015;43:W213–W219. doi:10.1093/nar/gkv404. Data: Los Alamos HIV Database, hiv.lanl.gov/catnap (assay and virus tables as downloaded).
9.Huang J, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody (10E8). Nature 2012;491:406–412. doi:10.1038/nature11544

Coverage Explorer.

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How these numbers were made

Sources