This Review, aimed at a broad scientific audience, provides an introductory guide to the history, development and immunological basis of vaccines, immunization and related issues to provide insight into the challenges facing immunologists who are designing the next generation of vaccines.
In this Collection, we bring you articles that highlight the latest research and insight into the immunology of SARS-CoV-2 and the associated disease COVID-19. They cover our emerging understanding of the immune response to this new coronavirus, prospects for vaccine development, immunopathology of COVID-19 and how it might be treated with immunomodulatory drugs.
Reviews & Perspectives
As the world races to develop vaccines against SARS-CoV-2, Dai and Gao highlight which viral targets are best to include in a vaccine and how this impacts the induced immune response and, ultimately, the safety and efficacy of a vaccine.
In this Perspective, Alon and colleagues discuss how insights into immune cell trafficking during pneumotropic influenza virus infections may inform our understanding of immune cell recruitment to the respiratory tract in patients with coronavirus disease 2019 (COVID-19). Moreover, they examine the emerging knowledge of vascular pathologies beyond the lung caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Are you new to virus research and trying to interpret the ever-expanding literature on immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Here, the authors compare the different assays and animal models used to measure immunity to SARS-CoV-2 infection and reconcile differences in apparent potency of antibodies assessed in different assays.
How does the discovery of SARS-CoV-2 cross-reactive T cells in unexposed individuals change our understanding of the COVID-19 pandemic? In this Perspective, the authors provide a thought experiment to explain why the discovery of cross-reactive T cells may affect disease severity in individuals, but is unlikely to change our estimate of the herd immunity threshold.
This Review outlines the guiding immunological principles for the design of coronavirus disease 2019 (COVID-19) vaccine strategies and analyses the current COVID-19 vaccine landscape and the challenges ahead.
Antibody-dependent enhancement (ADE) has been described as a mechanism that contributes to the pathogenesis of dengue virus infection. Limited evidence also suggests that it can also occur in other viral infections. Here, the authors explore the history of the ADE phenomenon, discuss the diversity of Fc effector functions and consider its potential relevance in the context of SARS-CoV-2 infection.
In this Progress article, Zeyu Chen and E. John Wherry summarize early reports of the T cell responses observed in patients with COVID-19, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.
Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.
Why are males more susceptible to severe COVID-19 than females? In this Perspective, Sabra Klein and colleagues consider the sex differences in the immune system that may contribute to this sex bias.
This Progress article from Merad and Martin examines our current understanding of the excessive inflammatory responses seen in patients with severe COVID-19. The authors focus on the emerging pathological roles of monocytes and macrophages and discuss the inflammatory pathways that are currently being targeted in the clinic.
In the short time since SARS-CoV-2 infections emerged in humans, much has been learned about the immunological processes that underlie the clinical manifestation of COVID-19. Here, the authors provide an overview of the pathophysiology of SARS-CoV-2 infection and discuss potential therapeutic approaches.
Here a group of leaders in the field define our current understanding of ‘trained immunity’, which refers to the memory-type responses that occur in the innate immune system. The authors discuss our current understanding of the key epigenetic and metabolic processes involved in trained immunity and consider its relevance in immune-mediated diseases and cancer.
Comments, Viewpoints, Web Watch
Somewhat surprisingly, individuals with asthma do not seem to have a greater risk of developing severe COVID-19. Here, the authors offer mechanistic insights to explain the epidemiological data.
In this World View article, eminent immunologist Peter Doherty suggests that we should consider the COVID-19 crisis as a training run for future, potentially worse pandemics and organize accordingly.
Here, Veldhoen and Simas discuss why immunity to SARS-CoV-2 in populations may ultimately be driven by the endemic presence of the virus and not rely on continued mass vaccination programmes.
In this Comment article, Sandy Douglas and Adrian Hill discuss the immunological considerations associated with a risk–benefit analysis for controlled human infection models of SARS-CoV-2.
Neurological symptoms are increasingly being observed in patients with COVID-19; this Comment article considers whether cross-reactive antibodies might contribute to the pathology associated with SARS-CoV-2 infection.
This Web Watch introduces the VaC tracker, a web resource that features an overview of the COVID-19 ‘vaccine landscape’, a clinical trials database and a ‘living review’ that distils the results of vaccine trials as they become available.
For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
During the current COVID-19 pandemic, the concept of herd immunity has become a topic of much debate. This Comment examines the factors that determine it, discusses how far we have come and considers what it will take to reach herd immunity safely.
Here, Cox and Brokstad briefly discuss T cell- and B cell-mediated immunity to SARS-CoV-2, stressing that a lack of serum antibodies does not necessarily equate with a lack of immunity to the virus.
In this Comment, Jeong Seok Lee and Eui-Cheol Shin discuss contradictory results regarding the downregulation or upregulation of type I interferon responses in patients with COVID-19 and the implications for therapies that target this pathway.
The corticosteroid dexamethasome has been shown to reduce mortality in patients hospitalized with COVID-19 who require mechanical ventilation. Here, the authors describe how this immunosuppressive drug might work.
In this Comment article, Becker and colleagues consider how the excessive release of reactive oxygen species by neutrophils may perpetuate red blood cell dysfunction, thrombosis and tissue damage in severe cases of COVID-19.
Recent studies have shown T cell reactivity to SARS-CoV-2 in 20–50% of unexposed individuals; it is speculated that this is due to T cell memory to common cold coronaviruses. Here, Crotty and Sette discuss the potential implications of these findings for disease severity, herd immunity and vaccine development.
In this Comment, Heidi Larson discusses the COVID-19 ‘infodemic’ and suggests the ways in which scientists can help to mitigate the spread of misinformation.
Why do some young and previously healthy individuals develop severe COVID-19? In this Comment, Casanova and colleagues suggest that monogenic inborn errors of immunity may be responsible based on lessons from other viral infections.
Rebecca Chandler from the Uppsala Monitoring Centre discusses how the COVID-19 pandemic could be the catalyst that propels vaccine safety surveillance into the twenty-first century.
In this Comment, Anne Rowley discusses what we know so far about the recently described multisystem inflammatory syndrome in older children associated with SARS-CoV-2 infection and how it differs from Kawasaki disease.
In this Comment, Jonathan Abraham highlights the potential of passive immunization strategies for COVID-19.
Beyond neutralization, antibodies have immune-modulating functions that can be protective but, in some cases, can enhance pathology. Understanding these functions is critical for the development of safe vaccines and antibody therapies for COVID-19.
Here, Peter Hotez and colleagues discuss the advantages of using an aluminium-based adjuvant in candidate COVID-19 vaccines.
In this Comment, Greg Lemke and Gregg Silverman propose that the excessive blood clotting and immune activation seen in severe COVID-19 may be mechanistically linked through protein S, a ligand for the immunosuppressive TAM receptor family.
In this Viewpoint article, members of the Optimmunize consortium discuss the evidence for non-specific and sex-differential effects of vaccines and how this information might inform vaccine design and policy, including in relation to the COVID-19 pandemic.
In this Comment, Michaela Gack and colleagues discuss how the dysregulation of type I interferon responses may contribute to COVID-19 pathology.
Here, Carmeliet and colleagues discuss the role of endothelial cells in inflammation and viral infection and propose novel therapeutic strategies for COVID-19.
Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.
Levels of the cytokine IL-17 positively correlate with disease severity in COVID-19. Here, the authors argue that existing anti-IL-17 therapies should be considered for the treatment of severe COVID-19.
Helminth co-infections can skew systemic immunity towards type 2 responses. Here, Bradbury and colleagues consider how this may impact the severity of COVID-19 in helminth-endemic regions.
Here, Hotez and colleagues highlight the two ‘faces’ of immune enhancement that could impact COVID-19 vaccine design.
This Comment article from Lambris and colleagues considers the therapeutic potential of targeting the complement system in patients with COVID-19.
This Comment article from the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describes their efforts to provide critical reviews of COVID-19 articles posted daily on the preprint servers bioRxiv and medRxiv.
Here, Iwasaki and Yang highlight the potential dangers of inducing suboptimal antibody responses to SARS-CoV-2. They stress the need for proper safety evaluation of candidate vaccines for COVID-19.
Immune-mediated inflammatory diseases are often treated with cytokine blocking therapy. This comment discusses whether such therapies may pose a risk — or even a benefit — in the context of the current COVID-19 pandemic.
In the short time since SARS-CoV2 emerged, much has been learned about the immunopathology of the infection. Here, Xuetao Cao discusses what these early insights imply for drug discovery and clinical management.
This preprint further characterizes a superantigen motif identified in SARS-CoV-2 spike protein and evaluates a monoclonal antibody targeting this region that can neutralize live virus.
Highlights and In Briefs
Two studies from the Oxford COVID-19 vaccine team describe the immune responses that develop in healthy adults following a single dose or two doses of their adenovirus vector-based COVID-19 vaccine.