Vaccine News: Oxford Led Study Shows That Spermidine From Plants (Originally Isolated From Semen) Boost COVID-19 Vaccine Protection In Elderly

Vaccine News: A new preliminary study led by researchers from Oxford University and includes scientists from University College London, Université de Strasbourg-France and University of Birmingham-UK shows that a natural compound called spermidine, which helps immune cells self-clean, may improve vaccine protection in older adults.


 
According to the study abstract, older adults are at high risk for infectious diseases such as observed at the recent COVID-19 outbreak and vaccination seems to be the only long-term solution to the pandemic.
 
Although most vaccines are less efficacious in older adults, little is known about the molecular mechanisms that underpin this. Autophagy, a major degradation pathway and one of the few processes known to prevent aging, is critical for the maintenance of immune memory in mice.
 
In this study the researchers show that autophagy is specifically induced in vaccine-induced antigen-specific CD8+ T cells in healthy human volunteers. In addition, reduced IFN secretion by RSV-induced T cells in older vaccinees correlates with low autophagy levels.
 
The study team demonstrates in human donors that levels of the endogenous autophagy-inducing metabolite spermidine fall in T cells with age. Spermidine supplementation of T cells from old donors recovers their autophagy level and function, similar to young donors' cells, in which spermidine biosynthesis has been inhibited.
 
The study findings show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB.
 
With these findings the researchers have uncovered novel targets and biomarkers for the development of anti-aging drugs for human T cells, providing evidence for the use of spermidine in improving vaccine immunogenicity in the aged human population.
 
The study findings were published in the peer reviewed journal: elife.
https://elifesciences.org/articles/57950
 
The study demonstrates that the chemical compound called spermidine that boosts the removal of cellular debris in immune cells may increase the protective effects of vaccines in older adults.
 
Spermidine is a aliphatic polyamine compound (C7H19N3) found in ribosomes and living tissues, and having various metabolic functions within organisms. It was originally isolated from semen.
 
Spermidine is a longevity agent in mammals due to various mechanisms of action, which are just beginning to be understood. Autophagy is the main mechanism at the molecular level, but evidence has been found for other mechanisms, including inflammation reduction, lipid metabolism, and regulation of cell growth, proliferation and death. https://www.karger.com/Article/FullText/356748
 
https://science.sciencemag.org/content/359/6374/eaan2788
 
Good dietary sources of spermidine are aged cheese, mushrooms, soy products, legumes, corn, and whole grains. Spermidine is also plenti ful in a Mediterranean diet. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022763/
 
For comparison: The spermidine content in human seminal plasma varies between approx. 15 and 50 mg/L (mean 31 mg/L). Wheatgerm a good source of spermidine contains about 243mg/kg, dried soyabean has 207mg/kg and chickpeas has 46mg/kg.
 
The study findings of this new research may lead to new approaches to protect older individuals from viruses such as the one causing the current COVID-19 pandemic and influenza.
 
Lead author Dr Ghada Alsaleh, a postdoctoral researcher at the Kennedy Institute of Rheumatology, University of Oxford, UK explained to Thailand Medical News, “Older adults are at high risk of being severely affected by infectious diseases, but unfortunately most vaccines in this age group are less efficient than in younger adults.”
 
In the past, Dr Alsaleh and colleagues showed that in older mice, immune cells may become less efficient at removing cellular debris, a process called autophagy, and this leads to a poorer immune response in the animals. In the current study, they looked at samples from young and older people participating in clinical trials for vaccines against the respiratory syncytial virus and the hepatitis C virus to see if the same event happens in human immune cells called T cells.
 
The study team found that autophagy increases in T cells from younger individuals after receiving vaccines, but this response is blunted in older people.
 
Interestingly when the study team examined T cells from the older individuals in the laboratory, they found that these cells have less of a natural compound called spermidine.
 
Spermidine ramps up autophagy and boosts T-cell function. Supplementing these older immune cells with spermidine in the laboratory restored autophagy to the same levels seen in T cells from younger people.
 
Autophagy degrades protein aggregates that accumulate with age and its age-related decline could contribute to “inflammaging”, the age-related increase in inflammatory cytokines in in blood and tissue. Loss of autophagy strongly promotes production of the inflammatory cytokines TNFa, IL-6 and IL1-b . https://pubmed.ncbi.nlm.nih.gov/22411934/
 
https://pubmed.ncbi.nlm.nih.gov/18849965/
 
https://www.karger.com/Article/FullText/370112
 
The study team previously found autophagy levels decline with age in human peripheral CD8+ T cells. Deletion of key autophagy genes leads to a prematurely aged immune phenotype, with loss of function in mouse memory CD8+ T cells, hematopoietic stem cell , and macrophages with a myeloid bias.
https://pubmed.ncbi.nlm.nih.gov/22302009/
 
https://pubmed.ncbi.nlm.nih.gov/25362489/
 
https://elifesciences.org/articles/03706
 
https://pubmed.ncbi.nlm.nih.gov/21339326/
 
Dr Alsaleh says, “Our work suggests that boosting autophagy during vaccination may help make vaccines more effective for older people.”
 
Importantly a small clinical trial recently tested whether giving spermidine to older adults would improve their cognitive function. As the results were positive, and spermidine did not appear to have any harmful effects, this provides some evidence that it would be safe to test whether spermidine might also be helpful for boosting the immune response of older people to vaccines. https://pubmed.ncbi.nlm.nih.gov/29315079/
 
https://pubmed.ncbi.nlm.nih.gov/31039826/
 
Senior author Dr Anna Katharina Simon, Professor of Immunology at the University of Oxford concluded, “Our study findings will inform vaccine trials in which autophagy-boosting agents, such as spermidine, are given in a controlled environment to older participants.It will be interesting to see whether these agents can enhance vaccination efficiency and help protect older people from viral infections.”
 
Interestingly, a few recent studies have also showed that spermidine might have antiviral effects on the SARS-CoV-2 virus. https://www.biorxiv.org/content/10.1101/2020.04.15.997254v1
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539557/
 
https://eit.europa.eu/news-events/news/eit-food-supported-spin-project-developing-nutritional-supplement-against-covid-19
 
Thailand Medical News strongly advises any individuals attempting to supplement with spermidine to only use plant sources as trying to procur it from other mentioned sources could be risky! Also always consult a licensed doctor for advice before consuming any supplements.
 
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