Immunity to SARS‐CoV‐2 infection

Over the past two and a half years, the SARSCoV2 pandemic has taken a heavy toll on human health worldwide. As of summer 2022, it is estimated that over 500 million people have been infected with SARSCoV2, and over 6 million people have died of COVID19.1 Yet in the midst of this overwhelming human tragedy, the SARSCoV2 pandemic has provided an unprecedented opportunity to study immune responses to a novel pathogen, its variants, and vaccines. These studies guided lifesaving COVID19 public health strategies, allowed for the realtime identification of immuneevasive variants, and revealed correlates of immune protection. Decades of prior research in virology, vaccinology, epidemiology, and immunology provided the foundation for these advances and for the rapid generation of SARSCov2 vaccines, over 11 billion doses of which have been administered. These vaccines, along with newly developed therapeutics, have saved millions of lives. During the time that these foundational scientific concepts were being built, not only were there very few women scientists, but those who contributed scientific findings were often not given due credit. During the SARSCoV2 pandemic, however, although still proportionately unjust,2,3 the contributions and impact of women's voices were immense. Women scientists, journalists, clinicians, and public health officials contributed to our daily understanding of this pandemic in previously unprecedented ways. In this issue, we celebrate the efforts and contributions of just a few of the outstanding scientists who also happen to be women, who have contributed to our understanding of the biology of SARSCoV2 infection, immunity to this pathogen, and production of lifesaving vaccines. Woven throughout these reviews one can also recognize the ongoing struggle for funding, recognition, collaborators, and even acceptance of the significance of specific lines of investigation. While my group did not contribute a review to this edition, we have contributed a cover image generated by Anna Hooser from the Benaroya Research Institute that was initially developed to represent our work exploring immunological mechanisms of “hybrid immunity”. 4 Hybrid immunity is the synergism between the responses to infection and subsequent vaccination that together promote the most robust and durable immunity against disease.5 Our team of extraordinary, collegial scientists, clinicians, research coordinators, and volunteers in Seattle first published evidence for lasting, functional immunological memory in response to SARSCoV2 infection within months of the beginning of the pandemic.6 We next embarked on understanding why individuals who were either previously infected or vaccinated were less protected than those who were infected first and then vaccinated thereafter. We found that the protective advantage of hybrid immunity likely stems from a combination of higher numbers of SARSCoV2specific memory B cells, higher neutralizing antibody titers, and infectionimprinted IFNgamma and IL10 cytokine production from CD4+ T cells. And while some of these different qualities could be normalized by additional antigen exposure via vaccination, others were not. The cover image is associated with this work, representing the immune response to SARSCOV2 infection (red) then to COVID vaccination (blue) and most recently to hybrid immunity (purple). The “sculpture” of the human immune response to SARSCoV2 became more complete as the pandemic and our immunological investigations continued. As stated by cofirst author Dr. Peter Morawski, who conceptualized the image, “Ivy is seen as a vigorous and aggressive plant, invasive and destructive, as was COVID19 on the world. The tallest pillar, hybrid immunity, rises the furthest above the ivy. ” After reading the reviews in this edition, I realized that this image, albeit originally for a different purpose, was also an appropriate analogy to highlight the importance of diverse responses as opposed to the homogeneous. Each investigator focuses on revealing a different part of the whole, and when their contributions are combined, a more complete picture emerges. Diverse responses are not only important in immunity but also in our research communities and study focus. Ensuring that we include diverse voices in science allows us to see the complete picture more efficiently.