The introduction of vaccines against Measles, Mumps, Rubella (MMR), and Varicella (the "V" in MMRV vaccines) led to a drop in the incidence of these diseases by 89% (Varicella) and 99% (MMR). These effective vaccines are a core component in most pediatric immunization programs across the world. Hence, every time a new pediatric vaccine is added to the existing immunization schedule, clinical evidence must be provided that the newcomer does not adversely influence the immunogenic response to the MMRV-licensed vaccines. These required non-inferiority studies when vaccines are co-administered (known as concomitant vaccine testing) come with their own challenges.
The Need for Quantitative and Functional Testing in an Evolving Landscape
For many years, data from qualitative MMRV testing has been used, somewhat uncontested by sponsors, regulatory agencies and the clinical research community. As more vaccines are introduced, the number of analyses required to pass FDA review increases. This scenario puts a significant strain on pediatric serum sample volumes, necessitating tighter sample logistics, careful planning of testing strategies, and ongoing development of multiplexing platforms.
There are significant changes in the market that are specific to MMRV testing. Merck's MMR vaccine, first licensed in the United States in 1971, was historically the only combination vaccine available in the US market (M-M-R® II (MMR) and ProQuad® (MMRV)). Recently, however, GSK's MMR vaccine, that received approval for use outside the U.S. in 1997, completed non-inferiority studies and is currently being reviewed for U.S. licensure. This has prompted a review of the way MMR and MMRV testing is performed. Even though many of the qualitative serological assays are calibrated against the respective WHO international standard (Dimech et al. 2016), challenges remain in terms of variability and their ability to estimate protective immunity. There is also a growing consensus that functional assays such as the Plaque Reduction Neutralization test (PRNt) for measles and PRNt or Hemagglutination Inhibition (HAI) for rubella etc. are considered the most appropriate test systems for a true assessment of immunity to infection (Cohen et al. 2008; Mancuso JD 2008; Dorigo Zetsma 2015). However, both PRNt and HAI are labor intensive, time consuming and require considerable expertise.
The race to develop and introduce new pediatric vaccines against Dengue, Chikungunya and Zika viruses in large regions of the world will increase the need for MMRV concomitant testing.
There is a need for high quality data generated using quantitative immune assays and PRNt testing that is calibrated using the respective IgG WHO international standard. For emerging vaccine developers and companies with very aggressive pipelines, it can be burdensome to utilize older qualitative "legacy" MMRV testing while concurrently developing and cross-validating new platforms. One issue is internal competition for resources as new products come down the pipeline with ever increasing complexity in the required testing. For some sponsors, moving MMRV testing from their labs into the CRO space is not a matter of "if" but a matter of "when," and most importantly "with whom."
Covance Vaccine and Novel Immunotherapeutic Laboratory
In late 2015, we launched the Covance Vaccine and Novel Immunotherapeutic Laboratory, a purpose-built unit equipped to support a wide array of vaccines and immunotherapeutic studies. It is powered by a co-located team of scientific and operational experts, solely focused on advancing vaccine and novel immunotherapeutic studies. In 2016, we surveyed different MMRV concomitant testing solutions, resulting in the validation of four quantitative immunoassays for the quantification of specific serum IgG antibodies to MMRV antigens.
The Covance Vaccine and Novel Immunotherapeutic Laboratory works in conjunction with other key areas of the business, including specimen management and logistics. When paired with our MMRV test offerings, we are able to maximize the generation of data from every sample, alleviating risks associated with increased per-sample concomitant test needs. We have extended our reach to >550 in-house assays and >3000 assays within the LabCorp esoteric testing network. Additional capabilities for custom assay development and/or transfer within an exploratory, GLP or CAP-CLIA environment enable us to address further testing needs in the concomitant space (Diphtheria, Tetanus and Pertussis).
The Bottom Line
The location of the Vaccine and Novel Immunotherapeutic Laboratory, at the heart of one of our clinical testing hubs (Indianapolis Covance Central Laboratory Services) allows us to provide a complete solution to current MMRV testing needs. We have the expertise and industry leverage to further develop our current test offerings into advanced, tailored MMRV testing solutions, and seamlessly integrate those into a sponsor's vaccine evaluation needs on a global scale.