Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure

Abstract

The evolution of circulating viruses is shaped by their need to evade the adaptive immune system. The spike protein which mediates entry to the host cell is the main target of antibody response. Because of the dense presentation of spikes on the viral surface, not all antigenic sites are targeted equally by antibodies, leading to complex immunodominance patterns. We used 3D coarse-grained computational models to estimate the antibody pressure on the seasonal flu H1N1 and the SARS subgenus spikes. Analyzing publically available sequences, we show that antibody pressure, through the geometrical organization of these spikes on the viral surface, shaped their mutability. Studying the mutability patterns of SARS-CoV-2 and the 2009 H1N1 pandemic spikes, we find that they are not predominantly shaped by antibody pressure. However, for SARS-CoV-2, we find that over time, it acquired, at low frequency, several mutations at antibody-accessible positions, which could indicate possible escape as define by our model. Hence, we offer a geometry-based approach to estimate and assess whether a pandemic virus is changing its mutational pattern to that indicative of a circulating virus.

Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants

“…Electron tomography estimates that SARS-CoV-2 virions have 25-127 spikes and a diameter of 80 nm ( Klein et al ( 2020 )). Even at the dense estimate of 127 spikes, this produces a density of 0.6 spikes per 100 nm2, which is half as dense as influenza (1.2 spikes per 100 nm2) ( Harris et al ( 2013 ); Amitai ( 2020 )). Thus, compared to the broadly neutralizing epitope on the stem of the influenza hemagglutinin spike, from a steric point of view, generating antibodies to the stem of the coronavirus spike may be more feasible.…”

“…Previous computational models of AM have focused on the response to single antigens ( Kepler and Perelson ( 1993 ); Oprea ( 1997 ); Brink ( 2007 ); Chan et al ( 2013 ); Meyer-Hermann et al ( 2012 ); Celada and Seiden ( 1996 )) or the development of broadly neutralizing antibodies (bnAbs) for influenza and human immunodeficiency virus (HIV) upon immunization with variant antigens ( Wang et al ( 2015 ); Sprenger et al ( 2020 ); Shaffer et al ( 2016 ); Amitai et al ( 2020 ); Chaudhury et al ( 2014 ); Childs et al ( 2015 ); Luo and Perelson ( 2015 ); Ganti and Chakraborty ( 2021 ); Sachdeva et al ( 2020 )). The latter studies aimed to study strategies for induction of bnAbs that target the conserved residues of the viral spike.…”