Broader neutralization of CT-P27 against influenza A subtypes by combining two human monoclonal antibodies

Abstract

There are several broadly neutralizing monoclonal antibodies that neutralize influenza viruses with different mechanisms from traditional polyclonal antibodies induced by vaccination. CT149, which is one of the broadly neutralizing antibodies, was also previously reported to neutralize group 2 and some of group 1 influenza viruses (13 out of 13 tested group 2 viruses and 5 out of 11 group 1 viruses). In this study, we developed another antibody with the aim of compensating partial coverage of CT149 against group 1 influenza viruses. CT120 was screened among different antibody candidates and mixed with CT149. Importantly, although the binding sites of CT120 and CT149 are close to each other, the two antibodies do not interfere. The mixture of CT120 and CT149, which we named as CT-P27, showed broad efficacy by neutralizing 37 viruses from 11 different subtypes, of both group 1 and 2 influenza A viruses. Moreover, CT-P27 showed in vivo therapeutic efficacy, long prophylactic potency, and synergistic effect with oseltamivir in influenza virus-challenged mouse models. Our findings provide a novel therapeutic opportunity for more efficient treatment of influenza.

Fig 1. In vivo efficacy of CT-P27.

Therapeutic and prophylactic efficacy of CT-P27 was observed in mice infected with a lethal dose of mouse-adapted A/California/04/2009 (H1N1) or A/Philippines/2/1982 (H3N2). Antibodies were administered 1 day after infection (A) or 14 to 1 day before virus challenge (B) and survival endpoints were monitored. Co-treatment effect of CT-P27 with oseltamivir was also investigated in mice. One day after challenging mouse-adapted A/California/04/2009 (H1N1), CT-P27 was administered once through intraperitoneal injection, with or without oral administration of oseltamivir for 5 days (C). This is a representative data from 2 repeated experiments.

Fig 2. Fc function for in vivo efficacy of CT-P27.

Mice were challenged with mouse-adapted A/California/04/2009 (H1N1) or A/Philippines/2/1982 (H3N2), and CT120, CT149, or double mutant was administered intraperitoneally after 24 hours. The survival rates were monitored for 15 days. This is a representative data from 2 repeated experiments.