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1.
Clin Exp Immunol ; 202(2): 162-192, 2020 11.
Article in English | MEDLINE | ID: mdl-32935331

ABSTRACT

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/immunology , Humans , Pneumonia, Viral/immunology , SARS-CoV-2 , Vaccination
2.
Mucosal Immunol ; 11(1): 290, 2018 01.
Article in English | MEDLINE | ID: mdl-28853440

ABSTRACT

This corrects the article DOI: 10.1038/mi.2017.46.

3.
Mucosal Immunol ; 11(1): 249-256, 2018 01.
Article in English | MEDLINE | ID: mdl-28537249

ABSTRACT

Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8+ Trm cells (CD103+/CD69+) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased interferon-γ in the airways of recipient mice, while CD4 transfer reduced tumor necrosis factor-α in the airways. Because DNA vaccines induce a systemic T-cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV-specific CD8 T cells, but they were immunopathogenic and not protective. Notably, there was a marked difference in the induction of Trm cells; infection but not immunization induced antigen-specific Trm cells in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen-specific airway cells.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Lung/immunology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/physiology , Respiratory System/immunology , Viral Vaccines/immunology , Adoptive Transfer , Animals , Cells, Cultured , Female , Humans , Immunologic Memory , Interferon-gamma/metabolism , Lung/virology , Mice , Mice, Inbred BALB C , Respiratory System/virology , Tumor Necrosis Factor-alpha/metabolism , Vaccination , Vaccines, DNA , Viral Load
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