Shelter from the cytokine storm: pitfalls and prospects in the development of SARS-CoV-2 vaccines for an elderly population

Abstract

The SARS-CoV-2 pandemic urgently calls for the development of effective preventive tools. COVID-19 hits greatly the elder and more fragile fraction of the population boosting the evergreen issue of the vaccination of older people. The development of a vaccine against SARS-CoV-2 tailored for the elderly population faces the challenge of the poor immune responsiveness of the older population due to immunosenescence, comorbidities, and pharmacological treatments. Moreover, it is likely that the inflammaging phenotype associated with age could both influence vaccination efficacy and exacerbate the risk of COVID-19-related “cytokine storm syndrome” with an overlap between the factors which impact vaccination effectiveness and those that boost virulence and worsen the prognosis of SARS-CoV-2 infection. The complex and still unclear immunopathological mechanisms of SARS-CoV-2 infection, together with the progressive age-related decline of immune responses, and the lack of clear correlates of protection, make the design of vaccination strategies for older people extremely challenging. In the ongoing effort in vaccine development, different SARS-CoV-2 vaccine candidates have been developed, tested in pre-clinical and clinical studies and are undergoing clinical testing, but only a small fraction of these are currently being tested in the older fraction of the population. Recent advances in systems biology integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly.

Exploring the Effect of Probiotics, Prebiotics, and Postbiotics in Strengthening Immune Activity in the Elderly

“…The composition of the GM differs between individuals and has emerged as an important immune modulator, closely associated with an individual’s health, including the risk of disease development. The cross-talk between the GM and the host’s immune system is achieved through molecular interactions after bioactive metabolites (short-chain fatty acids) are produced or through interactions with the host’s immune cells through cell-surface molecules (peptidoglycans and lipopolysaccharides) [ 10 , 18 , 19 , 20 ]. Notably, recent studies have reported the effects of the GM on the response to vaccination, including its stimulation of specific CD8 + -cell differentiation, B-lymphocyte growth and differentiation, and production of specific immunoglobulin A molecules (IgAs) [ 21 , 22 , 23 , 24 ].…”

“…Consequently, fewer naïve T cells are produced with time, and T-cell receptor variants become unable to diversify and respond to newly encountered antigens. Similarly, the ability of B cells to produce immunoglobulin also declines with age, as do the activities of neutrophils and natural killer (NK) cells [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Thus, the elderly is disproportionately affected by infectious diseases.…”

“…For instance, seasonal influenza causes substantial morbidity and mortality among the elderly, and this imposes a financial burden worldwide ( Figure 1 b) [ 11 , 12 , 13 , 14 ]. As the new global pandemic of coronavirus (COVID-19) surged in 2020, the elderly were at a significantly greater risk of infection, and had a significantly higher mortality rate, than any other age group, as reported by the World Health Organization [ 10 , 15 ].…”

The complex relationship between Immunosenescence and Inflammaging: Special issue on the New Biomedical Perspectives

“…Within such a complex scenario, recent advances in systems biology, integrating clinical, immunologic, and omics data can help to identify stable and robust markers of vaccine response and move towards a better understanding of SARS-CoV-2 vaccine responses in the elderly (See [8,16,24] in this issue). In particular, motivated by the still unclear immunopathological mechanisms of SARS-CoV-2 infection, Ciabattini et al stress that the design of vaccination strategies for older people is extremely challenging.…”

“…Moreover, among the different SARS-CoV-2 vaccine platforms that have been developed, only a few are being tested in the older fraction of the population. Ciabattini et al conclude that systems biology will help in addressing the complexity of this topic and in better understanding SARS-CoV-2 vaccine responses in the elderly ( [24] in this issue).…”