Scope and technology principle

The family of Paramyxoviruses includes common disease agents such as measles, mumps and parainfluenza. Live recombinant vaccines against these diseases have greatly contributed to their reduction, especially in developed countries. The use of live recombinant viruses in vaccines thus represents a well-established method of conferring immunity against the pathogen.

 

With the advent of reverse genetics these viruses can also be used to introduce foreign genes, encoding foreign antigens, into their recombinant genome. For instance, insertion of an RNA segment into the recombinant measles genome encoding for an immune stimulatory protein derived from Plasmodium falciparum or HIV antigens could result in immune responses that could protect against malaria and AIDS. In such cases, because the recombinant viruses retain their high immunogenic properties, they induce a strong humoral and cellular response against both their own (measles) and the foreign (malaria or HIV) proteins. Crucell holds the exclusive rights to a patented cloning technique to engineer paramyxoviruses.

 

Availability

A plasmid and cell-line based system was developed to allow the easy insertion of heterologous genes into the measles virus (MV) vaccine genome and rescue of replication competent live recombinant vaccine candidate. The plasmids can accommodate single or multiple gene insertions before the recombinant viruses are rescued using quality-controlled mammalian cells. Additionally, a routine in-house developed method for small- and large-scale production of the recombinant measles vaccine is available.

Experience

The recombinant MV vaccine is a widely used and inexpensive tool for immunization against measles. It contains a well-characterized vaccine strain known for its safety and efficacy; a single application during childhood confers life-long protection. The experience with recombinant MV vaccine in the last decades has shown that a large number of vaccination doses can be produced easily and economically. Additionally, the MV-genome does not integrate into the host genome, adding another important safety feature. Moreover, the recombinant genome can be engineered to stably accommodate additional genes. Finally, due to the promising practical experience with applying the MV vector as an aerosol, a good potential exists for the efficient induction of a mucosal immunity against foreign antigens if mucosal immunity is essentially needed.