Safety of mumps vaccine strains
Extract from report of GACVS meeting of 29-30 November 2006, published in the WHO Weekly Epidemiological Record on 19 January 2007
At the request of the immunization Strategic Advisory Group of Experts (SAGE), the Committee was asked to update the 2003 comprehensive review of the safety of mumps vaccine strains, paying particular attention to the risk of vaccine-derived meningitis. A review of the safety profile based on an updated literature search and data provided by some vaccine manufacturers was presented to the Committee.
Similar to its previous review,5 GACVS noted that cases of aseptic meningitis and estimates of incidence rates have been reported following the use of Urabe, Leningrad–Zagreb, Hoshino, Torii, and Miyahara strains from various surveillance systems and epidemiological studies. Given the variability in the quality of these studies and in the methods used, no clear conclusion on differences in risk between these vaccine strains can be drawn. The data up to now have revealed low rates of aseptic meningitis and no cases of virologically proven meningitis following the use of Jeryl–Lynn and RIT 4385 strains. There is only limited information about the Leningrad-3 strain. No data were available to assess the safety of the S79 strain.
Mass vaccination campaigns using mumps–measles–rubella vaccine that contained mumps vaccine strains associated with an increased risk of aseptic meningitis have resulted in clusters of adverse events that disrupted programmes. Recognition of the clustering of cases of aseptic meningitis has potentially been enhanced during mass immunization campaigns due to increased sensitivity of AEFI surveillance. This has been observed with Urabe and Leningrad–Zagreb strains. As of the date of this meeting, all reported cases of vaccine-derived mumps meningitis have recovered. Some of these were laboratory diagnosed cases and had little, if any, clinically significant disease. Despite the occurrence of these cases, the perceived risk–benefit ratio of utilization of the Urabe and Leningrad–Zagreb mumps vaccines over several years in routine programmes in developing countries has been considered acceptable. However, if mumps vaccine strains that have been associated with an increased risk of aseptic meningitis are to be used in mass campaigns, immunization programmes should implement appropriate strategies for communicating risk and managing cases in order to handle possible reports of clusters of aseptic meningitis.
Further studies undertaken to compare the safety profile of different mumps vaccine strains should be carefully designed to discriminate between potential strain variability and age-specific risk in different populations. Standardization of case definitions and quantification of severity will help in interpreting results.
GACVS is pleased with the steps taken to establish a repository of mumps vaccine virus strains at the National Institute for Biological Standards and Control, Potters Bar, England, and urges the acceleration of work to gain insight into the biological determinants of risk from the different strains. The Committee requests to be informed of any new data pertaining to the safety of mumps vaccines so that a better assessment can be made of the risk of aseptic meningitis or other conditions associated with specific strains.
5See No. 32, 2003, pp 282–284.
Switch from rubella vaccine to mumps, measles and rubella vaccine
Extract from report of GACVS meeting of 3-4 December 2003, published in the WHO Weekly Epidemiological Record on 16 January 2004
The attention of the Committee was drawn to the unavailability of a monovalent rubella vaccine in some countries and to the need to provide a rubella-containing combination vaccine to postpartum women seronegative for rubella. GACVS is not aware of any safety issues that would restrict the provision of a rubella-containing combination vaccine in place of single rubella vaccine in those circumstances.
Full report of GACVS meeting of 3-4 December 2003, published in the WHO Weekly Epidemiological Record on 16 January 2004
Adverse events following mumps vaccination
Extract from report of GACVS meeting of 11-12 June 2003, published in the WHO Weekly Epidemiological Record on 8 August 2003
GACVS considered a comprehensive review of the world literature regarding the safety of mumps vaccination, with special attention being paid to the risk of vaccine-derived mumps meningitis. It was noted that higher rates of aseptic meningitis have been described for the Urabe, Leningrad–Zagreb and Leningrad-3 strain vaccines compared with the Jeryl–Lynn strain vaccine. The possible virological basis for this difference and/or the other characteristics of the product that might explain these differences are not known. Some of the variability observed in the risk of aseptic meningitis following use of the various mumps vaccine strains may reflect pre-existing immunity, in particular in older age groups, as well as the variable levels of sensitivity of surveillance and of diagnostic practices in different settings. A detailed final report of this review, in which the estimate of risks will be assessed, will be published in due course.
GACVS concluded that risk estimates vary between studies, reflecting differences in study settings and circumstances and in degrees of surveillance. The available data are insufficient to distinguish between the safety profile with regard to aseptic meningitis for Urabe, Leningrad–Zagreb and Leningrad-3 strains. The Committee is not aware of any cases of virologically proven aseptic meningitis following Jeryl–Lynn vaccine. If Urabe, Leningrad–Zagreb and Leningrad-3 strain vaccines are being used in mass vaccination campaigns, national immunization programmes need to take into account the potential for clustering of aseptic meningitis following the campaigns. The Committee noted that, until now, all reported cases of vaccine derived mumps meningitis have recovered. There is no known case with long-term sequelae.
GACVS further considered a proposal for a mumps vaccine virus strain bank, to be developed at the invitation of WHO, which has considerable potential scientific interest. WHO will give further attention to the possibility of such a strain bank being established.
Full report of GACVS meeting of 11-12 June 2003, published in the WHO Weekly Epidemiological Record on 8 August 2003
Related links
Statement on adverse events following mumps vaccination
January 2004
The Global Advisory Committee on Vaccine Safety (GACVS) considered a proposal for an international reference laboratory for mumps virus isolates and the development of a mumps vaccine virus strain bank at its ninth meeting in Geneva, Switzerland on December 3-4, 2003. Parotitis and aseptic meningitis have been described as complications of mumps vaccination with Urabe, Leningrad–Zagreb and Leningrad-3 strains of the vaccine but not with the Jeryl–Lynn strain1. GACVS noted that now that all mumps virus strains can be characterized by polymerase chain reaction and nucleotide sequencing, it should be possible to address scientifically a number of unresolved questions regarding vaccine safety. These include defining the molecular determinants of virus attenuation, precise genetic determinants of virulence, safety of vaccines in relation to either pure or mixed virus populations in the vaccine and their antigenicity, determining at what stage point mutations occur in the virus (in passage, during replication in the body, or both), and the presence of sub-variant viruses in different vaccines. The Committee recommended that a hypothesis that single point mutations at certain positions of the haemagglutinin–neuraminidase protein gene region of the genome might be associated with post-vaccination aseptic meningitis should be further investigated. Such knowledge would improve current understanding of genetic and molecular characteristics of strains used for production of mumps vaccines. Moreover, further investigation may help to define the safety and immunogenicity profile of mumps vaccines. If molecular assays could distinguish wild-type from vaccine strains of the mumps virus, it would improve the quality control of existing and future vaccines. GACVS has recommended to WHO that an international reference laboratory for mumps virus isolates from vaccinees should be established.
GACVS also took note of the updated review of the safety of mumps vaccine virus strains, which showed that while existing data show different rates of parotitis associated with the different mumps vaccine strains, the data are insufficient to be extrapolated to differential risks for aseptic meningitis. The Committee had previously considered this review at its June 2003 meeting1, and concluded that risk estimates of vaccine-derived mumps meningitis vary between studies, reflecting differences in study settings and circumstances, and degrees of surveillance. The Committee further concluded that available data are insufficient to distinguish between the safety profile with respect to aseptic meningitis for Urabe, Leningrad-Zagreb and Leningrad-3 strains. If Urabe, Leningrad-Zagreb and Leningrad-3 strain vaccines are being used in mass vaccination campaigns, national immunization programmes need to take into account the potential for clustering of aseptic meningitis following the campaigns.
1WER No. 32, 2003, pp. 282–284