ABSTRACT
Most gene-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are nonreplicating vectors. They deliver the gene or messenger RNA to the cell to express the spike protein but do not replicate to amplify antigen production. This study tested the utility of replication in a vaccine by comparing replication-defective adenovirus (RD-Ad) and replicating single-cycle adenovirus (SC-Ad) vaccines that express the SARS-CoV-2 spike protein. SC-Ad produced 100 times more spike protein than RD-Ad and generated significantly higher antibodies against the spike protein than RD-Ad after single immunization of Ad-permissive hamsters. SC-Ad-generated antibodies climbed over 14 weeks after single immunization and persisted for more than 10 months. When the hamsters were challenged 10.5 months after single immunization, a single intranasal or intramuscular immunization with SC-Ad-Spike reduced SARS-CoV-2 viral loads and damage in the lungs and preserved body weight better than vaccination with RD-Ad-Spike. This demonstrates the utility of harnessing replication in vaccines to amplify protection against infectious diseases.
ABSTRACT
Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/µl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.