The COVID-19 Textbook



Antibodies in COVID-19

Mehak Zahoor Khan • Rachel Leeson • Carole Henry • Galit Alter

Introduction Antibodies Fc-Receptors Antibody Effector Functions Fc-Mediated Effector Functions Importance of Antibodies in Control of COVID-19 Role of Antibodies Following Vaccination Next-Generation Vaccine Challenges for COVID and Beyond Variants of Concern Preventing Transmission Optimized Boosting Monoclonal Antibodies as Therapeutics mAb Targets Next-Generation Monoclonal Antibodies Newer Gene Delivery Strategies Conclusion

INTRODUCTION Antibodies, or immunoglobulins (Igs), were first mentioned in the literature in 1890, when Emil von Behring and Shibasaburo Kitasato published diphtheria serum transfer studies, referring to neu tralizing agents, or “antikörper,” in the blood of immunized animals that conferred pathogen-specific immunity. 1,2 A decade later, Paul Ehrlich proposed the side-chain theory, describing antibodies as branched molecules containing multiple “lock-and-key” binding sites. Although it was incorrectly described as “chains” that grew out from the cell, the lock-and-key mechanism was confirmed in the 1940s by Linus Pauling, 3 who demonstrated the exquisite specificity conferred by these serum pro teins. Molecular structural work on antibodies was published in 1959, in independent studies from Gerald Edelman and Rodney Porter. 4,5 In 1948, Astrid Fagraeus deepened the understanding of the source of these molecules, demonstrating the highly specialized role of plasma cells that produce an tibodies. This was followed by the publication by Frank Burnet and David Talmage describing clonal selection theory in 1957, 6 a theory that was experimentally confirmed in a 1958 publication by Gustav Nossal and Joshua Lederberg. 7 However, the major explosion in antibody research occurred after Georges Köhler and César Milstein developed a method to produce monoclonal antibodies (mAbs) in vitro, 8 in 1975, greatly expanding our ability to study antibodies and explore their ther apeutic and research applications. mAbs now represent the fastest growing class of drugs, 9,10 with

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