Clinical applications of attenuated MVA poxvirus strain

Abstract

The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as a vector delivery system and as a vaccine candidate against a broad spectrum of diseases. This has been largely recognized from research on virus–host cell interactions and immunological studies in pre-clinical and clinical trials. This review addresses the studies of MVA vectors used in phase I/II clinical trials, with the aim to provide the main findings obtained on their behavior when tested against relevant human diseases and cancer and also highlights the strategies currently implemented to improve the MVA immunogenicity. The authors assess that MVA vectors are progressing as strong vaccine candidates either alone or when administered in combination with other vectors.

Keywords::

• cancer
• clinical trials
• infectious diseases
• modified vaccinia virus Ankara
• vaccines
• vector improvements

Financial & competing interest disclosure

The Esteban's laboratory is supported by Spanish grants (SAF2008-02036, FIPSE 36344/02, Red de SIDA RD12/0017/0038) and the Bill and Melinda Gates Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The attenuated modified vaccinia virus Ankara (MVA) strain is being considered as a vaccine delivery vector for different antigens, with the aim to trigger specific immune responses in the host that might lead to protection against a disease.

• • Multiple MVA recombinants expressing antigens of viral, bacterial, parasitic and tumor origin have been generated against a wide range of infectious diseases, like HIV/AIDS, influenza, hepatitis B and C, malaria, tuberculosis and cancer.

• • The signaling pathways triggered in response to MVA infection of macrophages and dendritic cells have been defined and shown to use different targets.

• • The impact of MVA in an organism has been characterized in pre-clinical and clinical studies through detailed analyses of innate, adaptive and memory immune responses.

• • In humans, MVA vectors expressing different antigens activate both CD4 and CD8 T cell responses that are broad, polyfunctional and of effector memory phenotype.

• • Genetic manipulation of MVA has been used to improve the vector immunogenicity by the targeted deletion of viral immunomodulatory genes.

• • System biology approaches are been pursuit to define correlates of protection.