Introductory article for Immunological Reviews, Vol 310 (2022)

The emergence of a coronavirus, SARS-CoV-2, first identified in Wuhan, China, at the end of 2019, has had a devastating effect on humanity. It is estimated that approximately 15 million have died of COVID-19 disease to date, and morbidity is many fold higher. The economic damage caused by the pandemic is huge. It has been estimated that the costs in terms of lost global GDP will amount to $22 trillion dollars by 2025. However, there is little doubt that the death toll and the damage could have been much worse were it not for the rapid development of vaccines and therapies to respond to SARS-CoV-2. These rapid developments were undoubtably facilitated by research that has gone on understanding viruses and the interplay between viruses and the immune system in the last two decades. In particular, it is noteworthy that HIV researchers have made some of the key contributions to our understanding and response to SARS-CoV-2. The emergence of variants of concern shows that there is still some way to go in gaining acceptable control of the pandemic, so that continued research will be necessary. Furthermore, the COVID pandemic is a wakeup call with regard to the vulnerability of our global population to rapidly spreading infectious disease. We need to prioritize greater understanding of pathogens with pandemic potential and develop the tools to respond to them to an even higher level than we have today. In this volume, we bring together contributions from a number of leading scientists in the response and understanding of SARS-CoV-2. In the first chapter, Stanley Plotkin and his colleagues David Goldblatt, Galit Alter, and Shane Crotty1 consider the correlates of protection for SARS-CoV-2. They discuss the importance of protective antibodies but also consider cellular responses and the importance of mucosal responses. Alexandra Sette and Shane Crotty2 then consider in detail immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. They refer to the unique opportunities provided by the pandemic to carry out detailed human longitudinal and cross-sectional studies comparing infection and vaccines from multiple platforms and in multiple cohorts of individuals. The knowledge gained from this pandemic will undoubtably help us in approaches to future pandemics. One of the great successes of the SARS-CoV-2 pandemic responses has been the rapid development of vaccines to protect against infection. Hanneke Schuitemaker and her colleagues Mathieu Le Gars, Jenny Hendriks, Jerald Sadoff, Martin Ryser, Frank Struyf, and Macaya Douoguih3 explore the immunogenicity and efficacy of an Ad26 adenoviral vector-based COVID-19 vaccine. This vaccine was employed quickly and is an important part of booster regimens to support ongoing efforts in the pandemic. One of the active centers for research during the COVID-19 pandemic has been South Africa, where early warning was given to the emergence of variants of concern. In their chapter, Jinal Bhiman and Penny Moore4 describe how existing global virology and immunology networks built for HIV vaccine research proved extremely important in response to the SARS-CoV-2 pandemic. Much of the infrastructure and expertise established in South Africa has been invaluable in mapping and preparing for shifts in the pandemic. Another important aspect of responses to the pandemic has been the ability to understand neutralizing antibody responses to the virus at the molecular level. Hejun Liu and Ian Wilson5 describe current molecular understanding of how the virus enters host cells and how the antibody system, through neutralizing antibodies, is able to prevent or reduce infection. Characterization of neutralizing epitopes is crucial, as we seek to design next-generation vaccines and therapeutics to respond to the development of variants of concern and to establish platforms for pandemic responses in general.