Reverse Genetics of Measles Virus and Resulting Multivalent Recombinant Vaccines: Applications of Recombinant Measles Viruses

Abstract

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses ( Mononegavirales ), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load

Applications and challenges of multivalent recombinant vaccines

“…16 The so-called quasispecies concept for RNA viruses have been explored. 16 Therefore, it is necessary to set quality control procedures to assure fitness and suitability of an expression vector for clinical development. Figure 1 shows a comparative study between an attenuated MV "lab strain", the authentic vaccines and the cloned vector from an authentic-parental vaccine.…”

“…6 Replicating viral vectors infect and reproduce in cells using the cell's machinery. 16,21 The new copies of the virus generated can subsequently infect other cells but because it has been manipulated it cannot cause disease. Several replication-incompetent viral vectors have been tested in clinical trials for HIV vaccines, including Adenovirus and adenoassociated virus, alphavirus and poxvirus.…”

“…18 Replication competent viral vectors like measles virus, vesicular stomatitis and rabies viruses, have been tested with varying levels of success in preclinical studies in animals. 16,19,21 Some vaccine developers are focusing on the use of replicating vectors in clinical trials, as they are more fruitful in animal studies in activating elements of innate immunity, the first responders to an invading organism, and are more likely to induce stronger cellular and mucosal immune responses and antibodies. These effects are achieved at much lower doses than the non-replicating vectors.…”

“…These effects are achieved at much lower doses than the non-replicating vectors. 16,17 Live attenuated viral vectors induce strong, long-lasting immune responses against the expressed proteins, including antibody and T cell responses in the blood, and many generate immune responses at mucosal surfaces, depending on their cell targets and sites of replication. 24 Importantly, immune responses immunizations.…”

“…Viruses have evolved sophisticated structures and mechanisms to infect cells, and hence, they serve as efficient delivery vectors of various antigens, 15 namely the HIV genes. [15][16][17] Scientists use viruses other than HIV as delivery vehicles or vectors to transport and express HIV genes. The modular nature of viral genomes allows scientists to insert foreign genes and sometimes replace the vector's own genes with the desired HIV or other genes.…”