Dr. Sette is currently a Professor at the La Jolla Institute’s Center for Infectious Disease and Vaccine Discovery, and Adjunct Professor in the Department of Medicine, of the University of California San Diego. Dr. Sette he studied in Biological Sciences from the University of Rome and did postdoctoral work at the National Jewish Center for Immunology and Respiratory Medicine in Denver, Colorado. In 1988, Dr. Sette joined Howard Grey, M.D. at the newly founded Cytel, in La Jolla, and was also appointed as an Adjunct Assistant Professor at The Scripps Research Institute. He founded Epimmune in 1997, where he served both as Vice President of Research and Chief Scientific Officer until 2002, when he joined LJI.
Host: “Prof. Alessandro Sette, you are currently head of LJI’s Division of Vaccine Discovery as well as chair of the Institute’s Center for Infectious Diseases at La Jolla Institute of Immunology in San Diego. What is the research field in which you are specifically engaged?”
Guest: “I have devoted more than 30 years of study to understanding the immune response, measuring immune activity and developing intervention strategies against cancer, autoimmunity, allergies and infectious diseases. My approach is to find out very patiently what are the molecules or fragments of viruses, bacteria or other substances (epitopes) that the immune system recognizes. We use this knowledge to measure and understand immune responses.
This research allows us to understand how the body successfully fights infection and, on the contrary, how pathogens escape the immune system, leading to disease. This is also important for analyzing the responses induced by vaccines, which must emulate the successful response, and not the one that does not protect against disease.
From the start the mission of our group at La Jolla Institute has been to share information and results with all scientific community worldwide. Consistent with this philosophy since 2003 I have created and managed the IEDB, Immune Epitope DataBase, which catalogues all data available in the scientific literature related to immune reactions to microbes, allergens and autoantigens.
The IEDB is freely available toward all researchers who need to use it.”
Host: “At this dramatic moment due to the COVID-19 pandemic, there is a great expectation to reveal the still unknown sides of this virus. At what point is the state of research?”
Guest: “In the case of COVID-19 we are moving on several fronts. On the one hand, we produced and published a bioinformatics study, which based on the data that were available already before the beginning of the epidemic (based on the SARS epidemic of 2003) allowed us to predict some likely targets that the immune system can hit in the COVID-19's case. Then we moved to recreate in the test tube, with synthetic antigens and blood donations from uninfected donors, what happens when an individual encounters the virus for the first time. In another line of research, we work with infected samples. An intriguing point is that the virus manifests itself in different ways. Some people become seriously ill, others in a less serious form, but there are also differences between one geographical location and another. In some regions the spread and severity of the infection takes on devastating outlines, in others it manifests itself blandly. We do not know the cause of these differences. They could be given by the variety of climatological conditions or by the speed with which the lockdown has been implemented or by the composition of the population with reference to age. On the hypothetical level, It is possible that cross-reactions with recent infections from other "benign" viruses, which cause colds, could give some protection against the SARS-CoV-2 infection.”
Host: “Currently in some countries of the world COVID-19 is starting to loosen its grip, but at the same time the threat of a second wave of contagion in the next autumn is weighing on it. High hopes lie in the discovery of a vaccine. In your opinion, what are the chances to have it in a short time?”
Guest: “One encouraging thing is that there are so many different vaccines that are being developed. So our hope is that there is not going to be a winner, but there are going to be many different winners. The vast majority of these different vaccine concepts rely on one particular protein, which is the spike protein. One important take home message from our study is that we saw very good responses, both in terms of killer and helper cells against the spike. This is really good news, because this was not a given. In this particular case, it so happens that it’s a good target for all three different types of immune response—which bodes well for people that are developing the spike-based vaccines. At the same time, our data found that there were responses also against other pieces of the virus, which suggests that maybe these other pieces could also be included to further fortify a vaccine concept, which could protect us even better.
In this context it is important to point out that different levels of protection could be achieved by different vaccines from the one which develops such a strong immunity, the so called “sterile immunity”- that prevent the infection from occurring, to the one that does not prevent infection, but still prevent disease and transmission, to the one which does not prevent disease but reduces the severity of the symptoms.”
Host: “Do you mean that at the end we are going to have on the market different vaccines?”
Guest: “Now we are experimenting a dramatic acceleration and tremendous effort to speed up the process of vaccine development. We are going to have competition, which is not necessarily bad. A likely scenario is that we are going to have several vaccines which will work, all different but several still based on common antigens or principles. If, for example, we have 20 vaccines working, then it will be easier to manufacture them, and more easily cover the global request.”
Host: “You were born in Italy and we know that you maintain strong ties to your homeland. Could you tell us if there are ongoing collaborations in this sector between Italy and the United States?”
Guest: “We are in constant contact with several Italian colleagues in various hospitals. Of course, Italy has a special place in my heart. But beyond the emotional and cultural roots, when Italy was already in the thick of the epidemic, the US was behind in terms of the timing of the epidemiological curve. We were able to establish several important collaborations on the start in several locations with several hospitals and research institutions. The groups of Vittorio Colizzi, in Tor Vergata (Rome ), Gilberto Fillaci at the Clinica Malattie Infettive e Tropicali Università di Genova, Mario Mondelli at Policlinico San Matteo of Pavia, Delia Goletti, allo Spallanzani di Roma, Luigia Pace, at the Italian Institute for Genomic Medicine (IIGM) of Turin, Vincenzo Barnaba, at Università della Sapienza in Roma.
Several of these groups with whom I collaborated in the past. I collaborated with Vincenzo Barnaba on studies on different aspects of immunology for several decades. I had worked with Delia Goletti on HIV and Tuberculosis and I knew Vittorio Colizzi since before leaving Italy for the States in 1985, our Italian colleagues sent us samples to be used in our analysis and we sent back our reagents. All these different contacts have been and continue to be very fruitful.”
Host: “ISSNAF in its mission aims to develop relations between North America and Italy in the field of research. In recent times in Italy, due to the pandemic, the importance of science has been reassessed. Often ignored, it has returned with bursting force to the attention of public opinion. An increase in economic aid has also been envisaged by the Italian government in the new economic maneuver to create more fertile ground for opportunities capable of attracting researchers.
Which choices at this time appear to be a priority?”
Guest: “In an emergency like the one we are experimenting it is important to foster exchanges and have a global approach. I wish COVID-19 will be the last global pandemic in history, but unfortunately, I do not think this is likely. Therefore, if we are going to have a second wave of it or if a new virus will appear, we must be prepared. We must not let our guard down, and we must be ready to face new emergencies. For this reason, it is extremely important to support the creation and maintenance of relevant infrastructures. We need support for science and healthcare. Italian researchers have done a fantastic job and deserve merit and credit. Everyone recognizes this, but at the same time more can be done in terms of prevention and reactive infrastructure. And action must be taken on the level of education, training, teaching in high schools, supporting researchers by financing their job. It is a challenge for Italy and the US alike, but the increase awareness originating from the COVID-19 pandemic can be a great opportunity to be learn and improve our societies.”
Professor and ISSNAF Founder
Alberto di Mauro
Camillo Ricordi currently serves as Director of the Diabetes Research Institute in Miami FL. He is the Chief Academic Officer of the Diabetes Research Institute of the University of Miami and is director of the DRI's Cell Transplant Center. He has been active in stem cell research and its applications to treating diabetes.
Ricordi held the role of Head of the Advanced CGMP (Current Good Manufacturing Practices) Advanced Cell and Biologic Product Manufacturing Facility (from 1993 to today), funded by the NIH (National Institute of Health), for research and clinical applications at the University of Miami in the United States and around the world. Ricordi has received numerous awards and prizes including the World Prize in Surgery (University of Geneva) for the development of a technology that has significantly contributed to the progress of surgery and the American Diabetes Association's outstanding Scientific Achievement Award. Ricordi is Official Knight of the Italian Republic (Order of Merit). He is also a member of the National Academy of Inventors, USA, and of the Superior Health Council (organ of the Italian Ministry of Health). He is recognized as a world leader in cell transplants and has conducted numerous clinical studies using UC-MSC in patients with type 1 diabetes, organ transplants and Alzheimer's, conducted over the past 20 years. He has been awarded 27 patents for inventions in the medical field. Ricordi has the supervision, guidance and general direction of this study on COVID-19. He will lead a team of investigators from the University of Miami - Miller School of Medicine.
The research conducted by Prof. Camillo Ricordi at the University of Miami is based on the use of mesenchymal stem cells of the umbilical cord for the treatment of serious cases of COVID-19.
Host: “Prof. Ricordi, what does this type of intervention consist in to combat COVID-19?”
Guest: “We are experimenting at the University of Miami with an intervention authorized by the FDA (Food and Drug Administration) in the USA. It is a randomized clinical trial that aims to verify the safety and efficacy of treatments that use stem cells from the newborn's umbilical cord.
COVID-19 is a highly contagious virus that can cause severe lung inflammation, making breathing difficult and insufficient. When oxygen levels in the bloodstream drop dangerously, vital organs stop functioning. In severe cases, the average time between the first symptom and the death of COVID-19 is only 8 days. The excess inflammation that occurs can take the form of an autoimmune disease or a reaction against the tissues of the body itself, with consequent damage to the pulmonary endothelium of the vessels and micro vessels that causes micro embolisms.
The human body reacts to these micro thromboses by activating plasmin, an enzyme predisposed to dissolve clots. But this enzyme ends up potentiating the virus even more, making it more infectious and virulent, in a chain reaction. Hence it is important to provide combination therapies that include anticoagulants and anti-inflammatories.
Stem cells can be compared to a technology that makes use of smart bombs: they have an anti-inflammatory action that at the same time moderates the immune system's responses (in fact they are used for autoimmune diseases such as diabetes, lupus etc.). They also have an antimicrobial, antibacterial and antiviral action, as well as promoting the repair and regeneration of damaged tissues.”
Host: “Why is your diabetic center at the forefront of the use of mesenchymal stem cells in COVID-19?”
Guest: “There are more than 9,000 international clinical trials in progress involving stem cells, while there are only 71 on COVID-19. Ours is the only pilot study conducted in Florida. In the cord there are mesenchymal stem cells that have already been approved for experimentation in Alzheimer's disease and type one diabetes. My team has been using it for 15 years for our clinical trials for type one diabetes, kidney transplants and Alzheimer's in collaboration with the neurology department of the University of Miami.
In the case of diabetes or kidney diseases, however, the use of mesenchymal stem cells presents an obstacle: if injected intravenously, the first filter is the pulmonary one. So far, therefore, 95% of the cells injected into patients have ended up in the lungs, forcing us to divert these cells to the target organ. But in our case the target organ is the lung and therefore the trial does not require subsequent surgical interventions to direct these cells elsewhere.”
Host: “Your team is carrying out this trial with various groups in the rest of the world including Italy. Can you tell us about the collaboration with your home Country? How was it born and how is it developing? Are there any more common projects in sight?”
Guest: “In Italy we are in contact with Prof. Massimo Dominici at the University of Modena and Reggio Emilia, who is coordinating a group of 5 centers, in which they will conduct research to compare the effectiveness of mesenchymal stem cells of different origins (from tissue adipose, placenta or bone marrow).
Furthermore, I am in contact with teams in China and Israel while in the USA I interact with Stanford and Harvard Universities. We have also started correspondence with other study centers in South America and Europe.”
Host: “It is obvious that at this moment the time value is very important. How long will it take to be sure of the good results of this trial?”
Guest: “In line with our spirit of collaboration without frontiers, our protocol is already available online on the CELLR4.org website, the official journal of the Cure Alliance foundation that supports our trial. It is a highly collaborative academic, non-profit initiative that aims to create a sort of bank of these cells, free of charge in the fastest and most efficient way possible.
Our trial is limited to 24 patients but we are planning to grow cells in sufficient numbers to distribute doses to a large number of hospitals in America.
In three months we will find out the outcome of our trial. We are optimistic and believe that we are on the right track.”