Pre-exposure antibody prophylaxis protects macaques from severe influenza.

Influenza virus pandemics and seasonal epidemics have claimed countless lives. Recurrent zoonotic spillovers of influenza viruses with pandemic potential underscore the need for effective countermeasures. In this study, we show that pre-exposure prophylaxis with broadly neutralizing antibody (bnAb) MEDI8852 is highly effective in protecting cynomolgus macaques from severe disease caused by aerosolized highly pathogenic avian influenza H5N1 virus infection.

Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem-specific human B cells.

The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10).

Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad Neuraminidase Inhibition by Human Antibodies.

Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedness and effective countermeasures, including monoclonal antibodies (mAbs). Here, we characterize human mAbs that target the highly conserved catalytic site of viral neuraminidase (NA), termed NCS mAbs, and the molecular basis of their broad specificity.

Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem.

Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response.