Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases

Abstract

Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses.

Figure 1

Ideal timeline for construction of an MVA-based vaccine after a human case of infection with a novel respiratory virus. Influenza virus is used as an example. (1) After the emergence of a novel respiratory virus with the ability of infecting humans, (2) the virus is isolated (3) and the sequence of a target gene of interest is obtained within a week. (4) Subsequently, the gene of interest is cloned or simply synthesized and subcloned into an MVA shuttle vector plasmid. (5) This shuttle vector is then transfected in cells infected with MVA. Through homologous recombination the gene of interest is inserted into the MVA genome. (6) By serial plaque passages on CEF, a good laboratory practice (GLP) compliant rMVA is clonally isolated . The process from cloning to obtaining the rMVA takes about 6–12 weeks.

Figure 2

Ideal timeline for evaluation of a novel MVA-based vaccine. (1) A newly developed rMVA vaccine (2) is tested in vitro to assess correct gene insertion and protein expression in rMVA infected cells, e.g., by Western Blot or flow cytometry. (3) Subsequently, the vaccine immunogenicity and efficacy is tested in mice, ferrets and/or macaques. (4) If the MVA-based vaccine is successful in the pre-clinical tests, the vaccine is tested in phase I, II and III clinical trails. (5) Finally, when the vaccine has proven safe and effective, it can be filed for market authorization.