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Universal Influenza Vaccine Clearly a Strategic Goal

Interview with Klaus Cichutek, president of the Paul Ehrlich Institute

20.04.2020 -

The Paul Ehrlich Institute is the German federal institute for vaccines and biomedicines. Klaus Cichutek has been president of the research institution and medical regulatory body since 2010. He earned a doctorate in biochemistry, is associate professor of biochemistry at the Johann Wolfgang Goethe University in Frankfurt and a member of numerous scientific and medical committees. We asked Klaus Cichutek about the vision and goal to develop a universal influenza vaccine.

CHEManager: Professor Cichutek, many vaccines are still being developed using chicken eggs. Is this process still up to date?
Klaus Cichutek: The manufacture of vaccines using chicken eggs or chicken fibroblasts is an established and proven process. Not every virus can be propagated in every cell culture system and the quality-assured manufacture as pre-defined in detail is an important part of the marketing authorization of each vaccine product. Therefore, it would not be appropriate to modify the production process of vaccines that are effective, of high quality and safe to use. In the case of influenza viruses, there is now also a cell culture vaccine. However, this represents a new development with its own specific marketing authorization, not a product variation.
Most established virus vaccines rely on other cell culture systems, such as human diploid or animal cell cultures. In addition, there are new approaches — so-called vaccine platforms — based on genetic material (RNA, DNA) or gene vector-based concepts such as the Modified Vaccinia virus Ankara (MVA) or attenuated measles virus, which are used to inoculate the genetic material of relevant and innocuous virus proteins. These three platforms (DNA, RNA and vectored vaccines) are also used by the currently most advanced developments against SARS-CoV-2.

What are the current major challenges in the development of new vaccines?
K. Cichutek: In vaccine development for the prevention of infectious viral diseases, some important prerequisites must be met. First of all, antigen structures (usually surface proteins of the pathogen) must be identified that mediate the induction of a protective immune response and remain conserved so that changes in the pathogen surface, such as those that constantly occur in influenza viruses during a season, do not lead to a loss of efficacy.
Prior to the first clinical trial it is tested in animals, whether the chosen antigen(s) or the gene(s) encoding the antigen(s) will mediate a specific immune response (immunogenicity). This means that they must not only trigger antibody formation, but also a sustained protective effect through the formation of neutralizing antibodies. Neutralizing antibodies inhibit virus spread in the body by inhibiting the entry of new viruses into additional somatic cells. In order to induce a real protective effect and the formation of these neutralizing antibodies, inactivated vaccines and vaccines consisting of purified or recombinant single pathogen components require a formulation including adjuvants as potentiators of the immune response. This applies to vaccines against viral diseases such as e.g. influenza, tick-born TBE and Japanese encephalitis. Attenuated live vaccines, such as those against measles, mumps and rubella, do not require adjuvants.
Manufacture under conditions of „Good Manufacturing Practice“ (GMP) must consistently result in and identical vaccine product, and ideally be fast and cost-effective.
As with all vaccines, local and systemic tolerability and the possibility of use in groups of persons particularly vulnerable to the infectious disease must be ensured. Ideally, the protective effect should also last for many years.

Which diseases pose particular challenges for vaccine developers?
K. Cichutek: With regard to the development of vaccines against SARS-CoV-2 infection and Covid-19 disease, it has been shown based on the experience gained during the development of vaccines against MERS coronavirus that neither inactivated adjuvanted vaccines nor live attenuated vaccines will be the preferred vaccine types.
To date, attempts to develop vaccines against for example human immunodeficiency virus HIV, hepatitis C virus (HCV), but also against novel pathogens such as Zika viruses and West Nile virus, have been less successful. The same applies to a universal influenza vaccine.
Initial successes with the new vaccine platforms have been achieved for Dengue and Ebola. Still, these vaccines are still under surveillance because open questions remain.

You mentioned the universal influenza vaccine. How far has development progressed in this area?
K. Cichutek: The development of a universal influenza vaccine is clearly a strategic goal, also of the WHO. Initial approaches are in the preclinical trials stage, and at least two vaccine concepts are in the first stages of clinical trial development. However, there is still no approach that seems to provide both very long-term protection and protection against „all“ possible variants or strains of influenza virus. All current approaches seem to solve only one of these two problems — which would still be an important first step. Cautious optimism is therefore permitted in this matter.

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Paul-Ehrlich-Institut