Seminars in immunology
-
SARS-CoV-2, the virus that causes COVID-19, emerged in late 2019, and was declared a global pandemic on March 11th 2020. With over 50 million cases and 1.2 million deaths around the world, to date, this pandemic represents the gravest global health crisis of our times. Thus, the race to develop a COVID-19 vaccine is an urgent global imperative. ⋯ In this review, we discuss emerging insights about the human immune response to SARS-CoV-2, and their implications for vaccine design. We then review emerging knowledge of the immunogenicity of the numerous vaccine candidates that are currently being tested in the clinic and discuss the range of immune defense mechanisms that can be harnessed to develop novel vaccines that confer durable protection against SARS-CoV-2. Finally, we conclude with a discussion of the potential role of a systems vaccinology approach in accelerating the clinical testing of vaccines, to meet the urgent needs posed by the pandemic.
-
Current management of severe asthma relying either on guidelines (bulk approach) or on disease phenotypes (stratified approach) did not improve the burden of the disease. Several severe phenotypes are described: clinical, functional, morphological, inflammatory, molecular and microbiome-related. ⋯ Based on the major immune-inflammatory pathway involved type-2 high, type-2 low and mixed endotypes are described for severe asthma, with several shared pathogenetic pathways such as genetic and epigenetic, metabolic, neurogenic and remodelling subtypes. The concept of multidimensional endotyping as un unbiased approach to severe asthma is discussed, together with new tools and targets facilitating the shift from the stratified to the precision medicine approach.
-
Inflammation is an essential response to injury and its timely and adequate resolution permits tissue repair and avoidance of chronic inflammation. Ageing is associated with increased inflammation, sub-optimal resolution and these act as drivers for a number of ageing-associated pathologies. ⋯ Alzheimer's Disease, atherosclerosis, obesity, diabetes and kidney disease. Detailed examination of the resolution phase of inflammation highlights the potential to harness these lipid mediators and or mimetics of their bioactions, in particular, their synthetic analogues to promote effective resolution of inflammation, without compromising the host immune system.
-
Seminars in immunology · Oct 2018
ReviewCorrelates of vaccine-induced protective immunity against Ebola virus disease.
Ebola virus disease is a deadly infection which occurs in sporadic outbreaks. Several vaccine candidates have been developed. The most advanced candidate is the recombinant VSVΔG-ZEBOV-GP vaccine, in which the Vesicular Stomatitis Virus (VSV) envelope glycoprotein is replaced by the Zaire strain Ebola virus (ZEBOV) glycoprotein (GP). ⋯ Despite significant progress in the characterization of vaccine-induced immunity, human correlates of protection against Ebolavirus infection have not yet been fully established. A systems biology approach, integrating clinical, immunological, transcriptomic and metabolomic data from pre-clinical and clinical vaccine studies, together with data from disease survivors, will be instrumental to identify Ebola vaccine correlates of protection. The information generated for the rVSVΔG-ZEBOV-GP vaccine may also help identify the correlates of protection of the other Ebola vaccine candidates.
-
Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. ⋯ We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.