Affinity of anti-spike antibodies to three major SARS-CoV-2 variants in recipients of three major vaccines

BACKGROUND: Measuring anti-viral antibody affinity in blood plasma or serum is a rational quantitative approach to assess humoral immune response and acquired protection. Three common vaccines against SARS-CoV-2—Comirnaty developed by Pfizer/BioNTech, Spikevax developed by Moderna/NIAID, and Jcovden (previously Janssen COVID-19 Vaccine) developed by Johnson & Johnson/Janssen (J&J)—induce antibodies to a variety of immunogenic epitopes including the epitopes located in the ACE2 receptor-binding domain (RBD) of the spike protein. Blocking RBD with antibodies interferes with the binding of the virus to ACE2 thus protecting against infection. METHODS: We perform measurements in the serum of the recipients of Pfizer, Moderna, and J&J vaccines, and we compare the apparent affinities of vaccine-induced antibodies against the RBD of the ancestral SARS-CoV-2 virus and the Delta and Omicron variants. We use our recently published method to determine the apparent affinity of anti-spike protein antibodies directly in human serum. This involves probing antibody-antigen equilibria with a small number of antigen-coated magnetic microparticles and imaging them on a fluorescence microscope. RESULTS: Recipients of two-dose Pfizer and Moderna vaccines, as well as recipients of the single-dose J&J vaccine, develop high-affinity antibodies toward RBD derived from ancestral SARS-CoV-2. Affinities of these antibodies to Delta-RBD are approximately 10 times weaker, and even more drastically reduced (∼1000-fold) toward Omicron-RBD. CONCLUSIONS: Vaccine-induced antibodies against ancestral SARS-CoV-2 RBD demonstrate ~10-fold and ~1000-fold weaker affinities toward Delta- and Omicron-RBD, respectively. Our approach offers a direct means for evaluating vaccine-induced adaptive immunity and can be helpful in designing or updating vaccines.