Bar graph of the highest reported molar neutralization ratios (MNRs).

<p>MNRs were reported for monoclonal antibodies against HIV <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Zhang1" target="_blank">[26]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Klein2" target="_blank">[27]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Ofek1" target="_blank">[28]</a>, RSV <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Wu1" target="_blank">[32]</a>, and influenza <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Schofield1" target="_blank">[31]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Edwards1" target="_blank">[33]</a>. The MNR for each antibody was calculated as the IC₅₀ of the Fab divided by the IC₅₀ of the IgG derived from in vitro neutralization assays (IC₉₀s were reported for some influenza IgG/Fab comparisons <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Schofield1" target="_blank">[31]</a>, but IC₅₀ ratios would be nearly the same because the slopes of the inhibition curves were similar). MNRs for a particular IgG/Fab combination can vary with the strain of virus being tested because the degree to which cross-linking can benefit an IgG depends on the affinity of the Fab for its antigen. Differences in size between a Fab and IgG may also influence the MNR if steric factors play a role in the neutralization mechanism of a particular antibody. However, this effect is probably minor, as (Fab)′₂ fragments generally exhibit similar neutralization potencies to their parental IgGs <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Schofield1" target="_blank">[31]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Edwards1" target="_blank">[33]</a>. Not shown are high MNR values (∼70) derived for IgG/Fab comparisons involving HIV virions with a gp41 cytoplasmic tail truncation <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Crooks1" target="_blank">[70]</a>. The tail deletion, which is rarely observed in vivo, has been suggested to increase the mobility of envelope trimers <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Crooks1" target="_blank">[70]</a> and/or increase the number of spikes per virion <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000908#ppat.1000908-Zingler1" target="_blank">[71]</a>, so its effects on intra-spike cross-linking are not well understood.