“Virus drift unlikely to make vaccine ineffective in the next few years”

“Virus drift unlikely to make vaccine ineffective in the next few years”

Dr Helmut Brunar is the CEO of Viravaxx AG — a Vienna-based, emerging biopharmaceutical company focused on the development of innovative antiviral vaccines and immunodiagnostics.

Before joining Viravaxx as CEO, he managed supply chain activities at Johnson & Johnson’s COVID-19 vaccine programme. Prior to this, he was CEO & Chairman with Axentis Pharma AG, where he built a team to develop respiratory drug candidate AX-TOBRA.

In a conversation with FM, Dr Brunar explains why, in the next 2-3 years, mutant SARS-CoV-2 will have to compete with the wild type virus till herd immunity is developed and why sub-unit vaccines are a necessity: Edited excerpts:

Viravaxx technology platform involves converting protein epitopes into potent antigens. Can you explain how this technology differs from that of conventional antiviral vaccines?

Viravaxx develops viral vaccines based on recombinant viral proteins — so-called subunit vaccines — by engineering derivatives thereof which have distinct advantages — such as enhanced immunogenicity — over simple recombinant proteins.

Mutating viruses are a big challenge to vaccine makers. Even in the case of SARS-CoV-2, the mutant strain has cast a shadow over the efficacy of the vaccines which have just started rolling out. Do you think novel technologies could overcome this problem? If so, how?

My spontaneous scientific answer to this question is yes. A top-line argument for my “yes” is that, for example, mRNA and vector technology can readily be adapted to effectively respond to escape mutations of SARS-CoV-2. Moreover, vaccine makers will, within the next few years, likely not face a situation in which virus drift makes the vaccines ineffective. This is due to the fact that such a drift – that is the virus’ answer to escape the immune response — is more likely if the majority of the population is immunized. This will not be the case within the next 2-3 years. Hence, during this period, virus mutations will have to compete against the wild type virus. In this competition, virus mutations will have to pay a penalty against wild type virus, leading to a dynamic state between the mutated virus and the wild type virus. It should also be noted that Viravaxx circumvents the problem of mutations by engineering vaccines for SARS-CoV-2 utilizing portions of the virus which undergo a low rate of mutations, because these portions need to be maintained by the virus in order to remain infectious.

Viravaxx’ current vaccine development pipeline targets some of the difficult viruses, including HBV, RSV and HRV. At what stage is your programme to develop a second-generation vaccine against SARS-CoV-2?

All our respiratory and COVID-19 programmes are early-stage. They all encompass subunit vaccine constructs. Moreover, all our vaccine constructs have a common technology platform, which allows us to design vaccine constructs (including vaccine constructs against SARS-CoV-2), analyze them with our two proprietary diagnostic tools, test them in animal immunization experiments, and then license them out to pharma partners to develop vaccine candidates. To be concrete, we are currently in the process of finishing the preclinical development of a subunit vaccine against SARS-CoV-2 which induces virus-neutralizing titres greater than 600 after two to three injections. We plan to move it into the clinical evaluation as soon as possible.

Viravaxx SARS-CoV-2 interaction assay has been described as a turning point in immuno-diagnostics. How do these microarrays aid in vaccine design?

Our SARS-CoV-2 interaction assay is a molecular interaction assay based on ELISA technology. With this assay, we can quantify the immune response, or the antibody response that inhibits the RBD-ACE2 interaction. The beauty of the assay is its simplicity and the fact that clinical laboratories do not have to work with the real virus but can mimic the real-life situation with a simple serum-based assay.

The assay can be used to identify patients who have developed, for instance, a strong neutralizing antibody response. I’ll just mention a few potential application fields: convalescent plasma therapy, checking antibody status between first vaccination and booster, checking antibody status in children, checking protective antibody response after infection… The assay is already being used in a clinical trial setting in Austria with full ethics committee approval.

One potential result of the aforementioned clinical study is that among the 800 samples that we analysed, we identified samples that exhibit an extraordinary strong protective immune response. We then run these samples on our second diagnostic tool, our proprietary microarray chip technology to longitudinally analyze the immune response – covering antibody response, T-cell response, B-cell response. With this approach, we obtain information about favourable specificities and properties of the protective response. We call this learning from epitope mapping of the natural protective immune response, a helpful platform tool for the industry for designing and developing vaccine candidates.

In summary, the combination of the two assays and the iterative procedure of measuring samples with both diagnostics tools is a valuable asset for identifying, shaping and improving vaccine candidates.

Going by the current vaccination approaches and manufacturing capabilities, how long will it take to immunize at least half of the world population?

A rough estimate for immunizing half of the world population could be 2-3 years. However, it is common knowledge that several parameters will have an influence on this. Among these are the ability of manufacturers to produce enough vaccines, affordability of the vaccines, logistics of vaccination in the different countries and the ability to distribute. As to distribution, we think that storage conditions of current vaccines are a disadvantage and that simple subunit vaccines are urgently needed.

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India seeks tie-up with Viravaxx

The government of India has evinced interest and sought collaboration with the Vienna-based Viravaxx AG in vaccine research and development against COVID-19.

Last August, the Indian ambassador in Vienna wrote a letter to Viravaxx exploring the possibility of joint research tie-ups in therapeutic and diagnostic areas, in addition to vaccines as part of the National Expert Group on Vaccine Administration for COVID-19 (NEGVAC).

 

“We have read with interest about your project to develop an integrated immunodiagnostic and vaccination programmes for COVID-19 together with the Medical University of Vienna,” states the letter.

NEGVAC was established to leverage domestic manufacturing capacity while also engaging with all international players for the early delivery of vaccines not only for India but also abroad, according to the letter.

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