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European Biopharmaceutical Review

The Future of Vaccines for Infectious Diseases

The COVID-19 pandemic has fast-tracked novel vaccine research and put the need for vaccine innovation centre stage. For viruses like HIV and cytomegalovirus (CMV), vaccine development has been unsuccessful despite years of research. To guide future vaccine research, it is important to understand how to engineer vaccines to engage all the immune system components in viral clearance more effectively. In general, current vaccine technologies do not fully leverage cytotoxic, or ‘killer’, CD8+, T cells, which are critical in the natural immune response (1). Engineered arenaviruses are being explored as novel viral vector-based vaccines and are promising for various reasons, including induction of potent CD8+ T cell responses and the ability to overcome the limitations of other vaccine approaches (2-4).

CD8+ T Cells Can Help Overcome Current Vaccine Limitations

Many vaccines rely on the development of antibodies as their mechanism of action. However, there is an increasing focus on vaccines that additionally induce adaptive cellular immunity, namely through the activation of cytotoxic CD8+ T cells, which are crucial in clearing viral infections and cancers. Although antibodies block viral internalisation, virus-specific CD8+ T cells clear infections by recognising viral fragments on the surface of infected cells and killing the infected cell (see Figure 1). Robust and long-term cellular responses, in particular CD8+ T cell responses, are essential to clear or control viruses linked to chronic infection, such as hepatitis B and C (HBV, HCV), CMV, HIV, and Epstein- Barr virus (1). However, to date, vaccines designed to trigger viral antigen-specific CD8+ T cells have not been clinically successful, due, in part, to insufficient induction and longterm maintenance of functional CD8+ T cells (1).

Viral vector-based vaccinations offer advantages over other vaccines, such as DNA-, RNA-, and peptide-based vaccines, by mimicking the natural course of viral infections (5). Nextgeneration viral vectors may induce more potent antigenspecific T cell responses that reinvigorate antiviral immunity in settings of chronic infection and immune exhaustion. Historically, adenoviruses and poxviruses have been used as viral vectors with varying degrees of success (5). Vector safety has been extensively tested, and most were well tolerated in clinical trials. However, for some viruses, including adenoviruses, efficacy can be hampered by pre-existing immunity to the vector backbone due to a widespread history of infection with wild-type viruses and the presence of virus-neutralising antibodies (nAbs). Possible immunity to the carrier may limit vaccine efficacy and reduce the benefits of immunity-enhancing booster shots (5). Research has focused on modifying viral vectors, or using viruses with low seroprevalence in humans to overcome pre-existing immunity, and identifying new viruses to leverage as vaccines.

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Klaus Orlinger PhD, HOOKIPA’s Executive Vice President of Research, has more than 10 years of experience generating and characterising prophylactic and therapeutic vaccines and immunotherapy candidates.

Henning Lauterbach PhD, HOOKIPA’s Vice President of Preclinical and Translational Research and Clinical Biomarkers, brings over 15 years of experience in academic science and preclinical development of lead therapeutic candidates.

Igor Matushansky MD, PhD, is HOOKIPA’s Chief Medical Officer and Global Head of Research and Development. His expertise is in translational and clinical research in oncology with prior leadership roles at Daiichi Sankyo and Novartis.

Daniel Pinschewer MD, Professor of Virology at the University of Basel, Switzerland, is one of HOOKIPA’s founders and chairman of its Scientific Advice and Review Committee. He has been recognised with national and international awards for his contributions to viral immunology.
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Klaus Orlinger
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Henning Lauterbach
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Igor Matushansky
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Daniel Pinschewer
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