Breadth of Vaccinated Cancer Patient Humoral Response to SARS-CoV-2 Spike Protein and RBD Variants

Abstract

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original Wuhan strain. (Breckenridge, 2021). B.1.351 RBD-foldon 2.2 antigen is identical to RBD-foldon 2.2, except it uses the B.1.351 variant RBD sequence. Using cancer patient sera samples, the breadth and robustness of response was examined in comparison to patients that indicated “no chronic conditions”. We hypothesized there would be a difference in humoral response to RBD-variant antigens in COVID-19 vaccinated cancer patients undergoing treatment vs patients with no chronic conditions. For sample selection, cancer patients were age/sex matched to individuals with no underlying health conditions, that received the same mRNA vaccine within 2 weeks of each other. To quantify antibody levels, ELISA end-point titers were performed. ELISAs detected levels of IgG and IgA antibodies against Spike, RBD-foldon, RBD-foldon 2.2, and RBD-foldon B.1.351. (Bushau, 2021). The statistical analysis used was a two-tailed student’s t-test to compare mean value of end-point titers between experimental and control groups. No significant difference between experimental and control groups for any antibody-antigen combination. B.1.351 RBD-foldon appears to elicit a lower response than RBD-foldon 2.2. Lower response may be explained by the mRNA sequence used in current vaccines encodes for original Wuhan SARS-CoV-2 spike protein. The platform is predictive of the level of antibody protection for variant screening

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