Covid-19 Vaccines — Immunity, Variants, Boosters

Abstract

T he coronavirus disease 2019 (Covid-19) pandemic has claimed an estimated 15 million lives, including more than 1 million lives in the United States alone.The rapid development of multiple Covid-19 vaccines has been a triumph of biomedical research, and billions of vaccine doses have been administered worldwide.Challenges facing the Covid-19 vaccine field include inequitable vaccine distribution, vaccine hesitancy, waning immunity, and the emergence of highly transmissible viral variants that partially escape antibodies.This review summarizes the current state of knowledge about immune responses to Covid-19 vaccines and the importance of both humoral and cellular immunity for durable protection against severe disease. A nti v ir a l Immunit yThe immune system is broadly divided into the innate and adaptive immune systems.Innate immune responses are the first line of defense against viruses and are rapidly triggered when cellular pattern-recognition receptors, such as toll-like receptors, recognize pathogen-associated molecular patterns.Innate antiviral immunity includes secretion of type I interferons, antiviral cytokines, and certain cellular responses, including neutrophils, monocytes and macrophages, dendritic cells, and natural killer cells. 1 Adaptive immune responses, the second line of defense against viruses, involve antigen-specific recognition of viral epitopes.Adaptive immunity includes two complementary branches of the immune system: humoral immunity and cellular immunity.Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) includes antibodies that bind the SARS-CoV-2 spike protein and either neutralize the virus or eliminate it through other effector mechanisms.2,3 Cellular immunity to SARS-CoV-2 includes virus-specific B cells and T cells, which provide long-term immunologic memory and rapidly expand on reexposure to antigen.B cells produce antibodies, CD8+ T cells directly eliminate virally infected cells, and CD4+ T cells provide help to support the immune responses.For acute viral infections, including SARS-CoV-2, it is likely that neutralizing antibodies are critical for blocking acquisition of infection, whereas a combination of humoral and cellular immune responses most likely controls viral replication after infection and prevents progression to severe disease, hospitalization, and death (Fig. 1).[4][5][6][7] For a highly transmissible SARS-CoV-2 variant that largely escapes neutralizing antibodies, cellular immunity may be particularly important for longterm protection against severe disease.