‘IVI has good researchers and product development people in one place’

Dr. Cecil Czerkinsky, Deputy Director-General for Laboratory Sciences 

Background 

Dr. Cecil Czerkinsky, former Director of the Mucosal Immunology and Vaccinology Division at INSERM (French National Institute of Health and Medical Research), joined the IVI in October 2005 as the Deputy Director General for Laboratory Sciences.  Dr. Czerkinsky has devoted his initial efforts to restructuring the laboratory division and to implementing new programs. This process requires instilling a research culture in the staff in order to motivate scientists and work towards common objectives. It also involves selecting sufficiently broad technology platforms to support highly focused multidisciplinary research programs that are relevant to the IVI mission.  Thus, laboratory research programs create synergies with other programs at IVI, such as Translational Research and the Pediatric Dengue Vaccine Initiative.  (Learn more about IVI´s Division of Laboratory Sciences)

Q: What are the main projects that the Lab is working on now?

One of the main objectives of the Lab at IVI is to build up a discovery platform that generates new knowledge and products relevant to vaccine development. IVI scientists are trying to identify new vaccines against certain bacteria and viruses, to develop new methods to produce these molecules in a cost-effective manner, new tests to monitor the type and strength of immunity induced by vaccines, new animal models of diseases caused by the microbes against which these vaccines could be tested, and novel “adjuvants” that could enhance the potency of vaccines.

A good example of Discovery has to do with how IVI scientists have identified novel antigens (structures recognized by the immune system as “foreign” to the body) on the surface of Shigella (dysentery) bacteria. Historically, the problem has been that most vaccine approaches have used antigens that are very specific to only certain species and serotypes of Shigella.  In practice you may have several Shigella species circulating at the same time, so for a classical vaccine to be useful, one would need multiple antigens. This can be a long and expensive process involving the development of various cocktails and conjugate vaccines.  IVI has taken a different approach. Its scientists have analyzed the Shigella genome to identify genes that are common to all Shigella species. IVI has identified several proteins encoded by these common genes, and work is in process to evaluate the protective properties of these new proteins as vaccine candidates in animal models. IVI was especially fortunate to have developed -- almost at the same time -- an animal model of intestinal shigellosis that mimicked the human disease. The development of this animal model constitutes another breakthrough because until recently, there have been no good animal models for testing intestinal shigellosis vaccines. (Read a related story).

In addition, the IVI laboratories are establishing methods to identify microbes in specimens collected in various field sites (Asia, Africa, Latin America) by Translational Research scientists, and to characterize these microbes at the molecular and genomic levels. Knowledge generated from the latter studies should permit IVI Translational Research scientists to gain better information about the patterns of spread of a given microbe within a given population and geographic area. In addition, these efforts should provide modern tools for improving the surveillance of disease outbreaks, a major activity of the IVI.

Strong basic research is a key element to fuel a successful discovery platform. For instance, IVI scientists are studying the mechanisms that are involved in regulating the body’s immune response induced by vaccines. IVI scientists are also exploring the possibility of administering vaccines without injection and are studying how vaccines administered at a particular location in the body (e.g. under the skin, in a muscle, through the mouth, into the nose) can spread immunity to the blood and to different organs (gut, lungs, genital tract, etc.). Such knowledge should help to better tailor vaccines and to design assays (tests) to assess the potency of vaccines to induce the right kind of immunity at the right place in the body.

IVI has recently embarked on an ambitious program to develop an effective influenza vaccine. The IVI approach has focused on flu antigens that are conserved among the different types of influenza viruses. Since seasonal flu vaccines are made yearly based on antigens which are subject to mutation, IVI’s approach has been to look for antigens that do not easily mutate.-- Flu vaccines are reformulated each year to respond to the prevailing strains of flu, which change from-year-to-year. That way one could have a reliable flu vaccine that does not need to be newly developed each year. IVI scientists have engineered one such antigen “conserved” among influenza viruses which is co-administered with a new adjuvant. It has been found to protect mice against different strains of influenza. The vaccine is also being given orally. This is a good example of interdisciplinary research involving scientists with expertise in molecular biology, virology, basic immunology, and vaccinology. 

Q: Can you tell us more about needle-free methods for delivering vaccines?

Ideally, vaccines should be given using the safest, cheapest, most convenient and least painful device. In other words, one should avoid syringes and needles if at all possible. However, this is not easy. The challenge has to do with cost and dose. For a needle-free method such as a drinkable or an inhalant vaccine or a skin patch, you generally need more vaccine than if you inject it. The question is, if you increase the quantity of the vaccine, can it be produced at an affordable cost? Finding formulations that facilitate passage of the vaccine into the host tissues when applied topically is an important area of research at IVI laboratories. An exciting finding by IVI scientists has been the development of an adjuvant that enhances absorption of vaccines administered by the mouth or through the nose, and at the same time strengthens immunity induced by the vaccine.

Q: Can you explain more about mucosal immunology?

Nearly 90 percent of infections are caused by microbes (viruses, bacteria, parasites) that enter the human body through mucosal surfaces, the protective inner coat that covers the lungs, intestines, reproductive tract, eye conjunctivae, ears, nose, and mouth. This is where most infections originate. So, ideally what we would like to do is bring about immunity at the right place -- the initial site of infection or the mucosa.  When we use injections, we stimulate the systemic immune system (blood, spleen, marrow) but we generally fail to induce robust immune responses in the mucosa. The best way to stimulate mucosal immune responses is to direct the vaccine to the mucosal system, which is located just beneath the mucosal surfaces. In order to do this, you have to ”trick” mother nature and by-pass natural barriers such as stomach acid, the thick mucus film, enzymes, etc.  Therefore, you need special delivery systems that can cross these barriers and direct the vaccine to the cells of the mucosal immune system.

Q: How do you monitor immunity when you’re testing a new vaccine?

A challenge in vaccine development in clinical trials is to predict if a vaccine will be effective.  Researchers typically do this by measuring the immune response in the body through blood samples. It is more difficult to measure a mucosal immune response. IVI has a good understanding of the roaming pattern used by immune system cells as they move from one organ to another. So scientists can pick up immune cells, induced by vaccination, during their transit in the blood system and predict their destination into specific organs. IVI scientists have developed a method which permits them to quantify these cells within a few hours after blood collection and at the same time determine the capacity of a given vaccine to induce either systemic or mucosal immunity or both. Because the test requires only a small blood sample, one can measure the immune response in small children and infants as easily as in adults. This method will soon be tested in several clinical trials coordinated by IVI, in collaboration with vaccine manufacturers and partner organizations in developing countries.

Q: What about transferring the vaccine production technologies to manufacturers in developing countries?

IVI’s mission is to accelerate the introduction of vaccines where they are most needed. We focus on successfully transferring vaccine production technologies to manufacturers in developing countries, in order to ensure a cost-competitive environment for vaccination programs that target the poor. To achieve this goal, the IVI Laboratory program hosts a unit dedicated to simplifying vaccine production methods and training staff from our vaccine manufacturing partners. This unit is made up of staff with extensive industry experience. Training takes place at the manufacturer’s facility, at the IVI, and in the laboratories of the IVI’s partner research organizations in the industrialized world.

As with drugs, vaccines must comply with international standards. So it is necessary to test products through quality control methods in a systematic, reproducible and standardized manner. The IVI Vaccine Technology Transfer Unit develops simplified methods for controlling the quality of vaccines. These methods are also transferred to manufacturers and to national regulatory agencies in developing countries.

It is unusual to have good researchers and good product development people in one place. IVI is unique in this way.