How to boost immune response to vaccines in older people
Apply immune expertise and some genital wart cream!
March 27, 2020
Science Daily/Babraham Institute
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy aging for an aging population. Immunologists have identified a route for counteracting the age-related loss of two key immune cell types by using genital wart cream to boost immune response to vaccination in aged mice. After this validation in mice, the findings offer an attractive intervention to tailor the make-up of vaccines for older people.
Research just published by the Linterman lab shows that the immune system of older mice can be given a helping hand by applying immunology expertise and some genital wart treatment (don't try this at home just yet)!
Mice and humans show similar age-dependent changes in their immune system so this finding offers hope for easily increasing the robustness of vaccination response in the older population.
As we age, the function of our immune system declines, rendering us more susceptible to infections, and making us less able to generate protective immunity after vaccination. By understanding the cellular and molecular mechanisms that underpin this poor response in older individuals, researchers in the Linterman lab were able to repurpose an existing treatment for genital warts, and demonstrate that this was effective in overcoming the age-related effects on two of the many cell types making up our immune system. The research is published online in the journal eLife.
Dr Michelle Linterman, a group leader in the Institute's Immunology research programme, said: "The current coronavirus pandemic highlights that older members of our families and communities are more susceptible to the morbidity and mortality associated with infectious diseases. Therefore, it is imperative that we understand how the immune system in older people works, and to explore how we might be able to boost their immune responses to vaccines to ensure they work well in this vulnerable part of our society."
Vaccines work by generating antibodies that are able to block the ability of pathogens to infect us. Antibody secreting cells are produced in the germinal centre, immune reaction hubs that forms after infection or vaccination. With age, the magnitude and quality of the germinal centre reaction declines.
Immune cells called T follicular helper cells are essential to the germinal centre response. In this study the team used mice and humans to investigate why T follicular helper cell numbers decline with age, and if there is a way to boost them upon vaccination.
"The germinal centre response is a highly collaborative process that requires multiple cell types to interact at the right place and the right time. Therefore, it made sense to us that defects in one or more of these cell types could explain the poor germinal centre response observed in older individuals after vaccination," explains Dr Linterman.
The researchers found that older mice and humans form fewer T follicular helper cells after vaccination, which is linked with a poor germinal centre response and antibody response. By developing our understanding of the cellular and molecular events occurring in the germinal centre after vaccination, the researchers identified that T follicular helper cells in older mice and people received less stimulatory interactions from their immune system co-workers. By using a cream (imiquimod, currently used to treat genital warts in humans) on the site of immunisation to boost the number of stimulatory cells, they were able to restore the formation of T follicular helper cells in older mice and also rescue the age-dependent defects in another immune cell type (dendritic cells). Encouragingly, this demonstrates that the age-related defects in T follicular helper cell formation in ageing are not irreversible, and can be overcome therapeutically.
The full picture and evaluation of whether this approach will work as an intervention in humans requires more research into why the germinal centre response changes with age, and what can be done to overcome this. Once achieved, it could be that clinical trials are established to incorporate this knowledge into new vaccine formulations for older people.
https://www.sciencedaily.com/releases/2020/03/200327113752.htm
COVID-19 vaccine development
February 26, 2020
Science Daily/Hong Kong University of Science and Technology
Scientists have recently identified a set of potential vaccine targets for SARS-CoV-2 coronavirus, to guide experimental efforts towards vaccine development against novel pneumonia (COVID-19).
A team of scientists at the Hong Kong University of Science and Technology (HKUST) has recently made an important discovery in identifying a set of potential vaccine targets for the SARS-CoV-2 coronavirus, providing crucial leads for guiding experimental efforts towards the vaccine development against the novel pneumonia (COVID-19) caused by the virus.
Like SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, SARS-CoV-2 belongs to the same Betacoronavirus genus. By considering the genetic similarity between SARS-CoV-2 and SARS-CoV, the team leveraged experimentally-determined immunological data to identify a set of SARS-CoV- derived B cell and T cell epitopes that exactly match to SARS-CoV-2. Epitopes are biomarkers recognized by the immune system to trigger actions against the virus. As no mutation has been observed in the identified epitopes among the available SARS-CoV-2 genetic sequences, immune targeting of these epitopes may potentially offer protection against the novel pneumonia COVID-19.
The team, led by data scientists Prof. Matthew McKay and Dr. Ahmed Abdul Quadeer, expected that their work can assist in guiding experimental research towards the development of effective vaccines against SARS- CoV-2.
Prof. McKay highlighted that "Despite similarities between SARS-CoV and SARS-CoV-2, there is genetic variation between the two, and it is not obvious if epitopes that elicit an immune response against SARS-CoV will likely be effective against SARS-CoV-2. We found that only roughly 20% of the SARS-CoV epitopes map identically to SARS-CoV-2, and believe these are promising candidates."
"For the identified T cell epitopes, we also performed a population coverage analysis and determined a set of epitopes that is estimated to provide broad coverage globally as well as in China" said Dr. Quadeer. The estimated population coverage represents the percentage of individuals within the selected population that are likely to elicit an immune response to at least one epitope from the identified set.
Prof. McKay is a Professor in the Departments of Electronic & Computer Engineering and Chemical & Biological Engineering; Dr. Quadeer is a post-doctoral fellow in the Department of Electronic & Computer Engineering. Their findings were recently published in the scientific journal Viruses this month.
"Our objective was to try to assist with the initial phase of vaccine development, by providing recommendations of specific epitopes that may potentially be considered for incorporation in vaccine designs" Prof. McKay added. "More generally, our work is part of a global effort seeking to capitalize on data for COVID-19, made available and rapidly shared by the scientific community, to understand this new virus and come up with effective interventions."
The beginning of 2020 has seen the emergence of SARS-CoV-2 outbreak in mainland China, which has quickly spread to over 30 countries around the world, infecting over 80,000 people and causing over 2,600 deaths as of late February 2020.
https://www.sciencedaily.com/releases/2020/02/200226091227.htm