Evidence before this study
tetanus, RBD
TETANUS
Early in the COVID-19 pandemic, there were authoritative calls for RBD-based SARS-CoV-2 vaccines that would potentially reduce the risk of vaccine escape and imprinting, and provide a more efficient basis for mass production to meet global vaccine needs.Recent post-marketing studies of omicron-directed whole Spike bivalent mRNA booster vaccines have shown only modest increases in immune responses to omicron variants compared to ancestral vaccine boosts. It is possible that imprinting is an important attenuating factor, and that it may become progressively more impactful as successive boosts are delivered.We developed two RBD-based vaccines: a recombinant protein beta variant RBD-Fc vaccine, combined with MF59® adjuvant, and an mRNA-beta variant RBD vaccine delivered in a liponanoparticle solution. Our preclinical studies showed that these vaccines induce strong protection in mice when challenged with both beta and a mouse-tropic ancestral strain. Furthermore, a heterologous third dose booster following immunisation with whole Spike vaccine, induced increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5.Several other RBD vaccines are in various stages of clinical trials or implementation. Some key examples are: (1) ZF2001 is now approved for emergency use in China and some other countries. This dimeric RBD vaccine has two RBD subunits linked via an engineered single-chain construct and administered with alum adjuvant. (2) A similar dimeric RBD vaccine, combined with tetanus toxoid plus alum, is also approved in Cuba and Iran. (3) An RBD human IgG1-Fc dimer, fused to IFN-α and an MHC class–II binding element, combined with alum, has recently been in phase III clinical trial. (4) An RBD-human IgGNone of these recombinant protein vaccine trials has investigated RBD constructs targeting the beta SARS-CoV-2, as a fourth dose heterologous boost, and none has compared protein to mRNA RBD vaccines in the same trial.