Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses
Mitch Brinkkemper, Tim S. Veth, Philip J. M. Brouwer, Hannah L. Turner, Meliawati Poniman, Judith A. Burger, Joey H. Bouhuijs, Wouter Olijhoek, Ilja Bontjer, Jonne L. Snitselaar, Tom G. Caniels, Cynthia A. van der Linden, Rashmi Ravichandran, Julien Villaudy, Yme U. van der Velden, Kwinten Sliepen, Marit J. van Gils, Andrew B. Ward, Neil P. King, Albert J. R. Heck, Rogier W. Sanders
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses. Inclusion of Beta spike improved neutralizing antibody responses against SARS-CoV-2 Beta, Gamma, and Omicron BA.1 and BA.4/5. A third vaccination with ancestral SARS-CoV-2 spike also improved cross-neutralizing antibody responses against SARS-CoV-2 variants, in particular against the Omicron sublineages. Second, we combined SARS-CoV and SARS-CoV-2 spike proteins to broaden sarbecovirus immune responses. Adding SARS-CoV spike to a SARS-CoV-2 spike vaccine improved neutralizing responses against SARS-CoV and SARS-like bat sarbecoviruses SHC014 and WIV1. These results should inform the development of broadly active SARS-CoV-2 and pan-sarbecovirus vaccines and highlight the versatility of two-component nanoparticles for displaying diverse antigens.