Academic journal article Bulletin of the World Health Organization

Clinical Safety Issues of Measles, Mumps and Rubella Vaccines

Academic journal article Bulletin of the World Health Organization

Clinical Safety Issues of Measles, Mumps and Rubella Vaccines

Article excerpt

Introduction

Some concerns have recently been expressed on the post-immunization safety of live attenuated measles vaccine and measles-mumps-rubella (MMR) vaccine because of reports which have proposed a possible link between measles virus vaccines or other paramyxovirus infections and the establishment of juvenile autism, Crohn disease (CD) and other forms of inflammatory bowel disease (IBD) (1-4). This hypothesis was based on observations which showed that wild measles infection at the neonatal stage could increase the risk of development of CD late in life (5, 6). The present review discusses the findings of experimental work carried out at the National Institute for Biological Standards and Control (NIBSC) and in other laboratories to identify the presence or absence of measles virus RNA in clinical tissues derived from IBD cases. In addition, some information on the virological components of MMR vaccine and tests carried out on them prior to release for human use is provided.

Virological background to MMR vaccine

Vaccines against measles, mumps and rubella are produced from live attenuated viruses which have been propagated in a variety of cell substrates, including embryonated chicken eggs and/or human diploid cells. Each component of MMR vaccine is initially prepared in the monovalent form, each of which is then mixed together to produce a trivalent form in which the component virus population is present in a well-defined quantity sufficient to induce an effective immune response in a vaccine recipient. In addition to the trivalent form, commercial preparations are also available in the monovalent form.

The genomes of all three viruses consist of a single-stranded RNA molecule that has negative polarity for measles and mumps and positive polarity for rubella. The genetic organization of various genes within the linear genome has been fully mapped and their sequence determined completely for a number of strains. However, the structure-function relationships of the viral genes, their protein products, and host-virus interactions at the nucleic acid and protein levels remain to be elucidated. There is a lack of understanding, at the molecular level, about the mechanism(s) of virus attenuation during multiple passages in embryonated eggs and cells derived from them or other sources. At present, the genetic domains that could be used as molecular markers to confirm whether the virus population present in the commercial formulations of MMR vaccines is effectively attenuated, or not, remain to be identified. These domains have been mapped and characterized at The molecular level for poliovirus (7) and their analysis provides good indicators about the neurovirulence potentials of vaccine lots before they are released for human use (8). The current regulatory requirements of MMR vaccine production demand a comprehensive evaluation of each candidate vaccine seed material for its virological, serological, and clinical safety, including evidence for the absence of neurovirulence in susceptible animals. The seed that passes the regulatory requirements is then used as the inoculum to generate vaccine production lots under standard manufacturing conditions. Product quality is maintained by ensuring production consistency between vaccine batches generated from the same seed. It is believed that at the molecular level the genomes of measles, mumps and rubella viruses are sufficiently stable, as there are no reports indicating the occurrence of genetic recombination. This is in contrast to the situation for poliovirus, the genetic stability of which is difficult to maintain because of RNA recombination and also the rapid reversion of the attenuating mutations within the genome. In the United Kingdom, every batch of MMR vaccine is routinely tested, prior to release, for its potency, thermostability and identity of its viral components using several virological and serological assays, and the product records are periodically reviewed. …

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