Measles Vaccination: New Strategies and Formulations

Rory D de Vries; Koert J Stittelaar; Albert DME Osterhaus; Rik L de Swart


Expert Rev Vaccines. 2008;7(8):1215-1223. 

In This Article

Live-attenuated Vaccine

In parallel with immunization with inactivated vaccines, live-attenuated MV vaccines (LAV) were introduced in the early 1960s.[6] The first attenuated virus used as a vaccine still led to rash and fever in 20–50% of children to whom it was administered,[7] and was eventually replaced with more attenuated strains. The worldwide application of LAV resulted in a major decline of measles fatalities,[8] with an impressive safety record even in HIV-seropositive subjects and immunocompromised individuals.[9] The success of the LAV was improved when many industrialized countries routinely introduced a second dose of vaccine.[10,11] In developing countries routine administration of a second dose is difficult owing to infrastructural problems. Here, supplementary immunization activities, such as mass-vaccination campaigns, are currently being performed to protect both nonvaccinated individuals and those with primary vaccine failures, and increase levels of community immunity.[12] By using these strategies, the number of deaths attributed to measles was halved by 2005 compared with 1999.[13]

Even though major progress has been made in interrupting endemic MV transmission, there are several limitations to the use of LAV. These limitations include the dependency on cold-chain maintenance, a (minimal) risk to the immunocompromised,[14] the requirement for professional healthcare workers, the availability of sterile needles and proper disposal of contaminated waste material. In addition, seroconversion rates observed after vaccination with LAV vary considerably. Some of these variations could be attributed to vaccine dose, vaccine strain, HLA phenotype or polymorphisms in human genes encoding Toll-like receptors, cytokines, cytokine receptors, CD46 or signaling lymphocyte-activation molecule.[15–18] However, the presence of maternal antibodies and immunological maturity of the recipient has the most significant influence on the success rate of measles vaccination.[19,20] A proportion of infants between 4 and 9 months of age have lost their maternally derived MV-specific antibodies, leaving them susceptible to wild-type MV infection. Vaccination at this age is not recommended because of the fact that other children still have maternal antibodies that will neutralize the vaccine virus and, thus, interfere with vaccination efficacy, leaving a so-called ‘window of susceptibility.' In addition, vaccination efficacy in young infants may also be impaired due to immaturity of the immune system.[21] Under ideal conditions, 95% of children seroconvert when vaccine is administered at 12 months of age,[22] 85% at 9 months[23] and only 67% below 9 months.[21] Two alternative approaches can be used to protect infants in this age group. If vaccination coverage in older age groups is sufficiently high, MV circulation will be interrupted, thus reducing MV exposure. As an alternative, new measles vaccines and delivery systems that could be used in young infants are being researched continuously with different success rates.


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