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, 385 (9984), 2297-307




Nathaniel Lambert et al. Lancet.


Rubella remains an important pathogen worldwide, with roughly 100,000 cases of congenital rubella syndrome estimated to occur every year. Rubella-containing vaccine is highly effective and safe and, as a result, endemic rubella transmission has been interrupted in the Americas since 2009. Incomplete rubella vaccination programmes result in continued disease transmission, as evidenced by recent large outbreaks in Japan and elsewhere. In this Seminar, we provide present results regarding rubella control, elimination, and eradication policies, and a brief review of new laboratory diagnostics. Additionally, we provide novel information about rubella-containing vaccine immunogenetics and review the emerging evidence of interindividual variability in humoral and cell-mediated innate and adaptive immune responses to rubella-containing vaccine and their association with haplotypes and single-nucleotide polymorphisms across the human genome.

Conflict of interest statement

Competing Interests

These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies.


Figure 1
Figure 1. Frequency of laboratory confirmed rubella cases age in years in the African Region, 2002–2009
Frequency of laboratory confirmed rubella cases (as reported by countries using measles case-based surveillance) by age in years with a cumulative age distribution curve, 2002–2009, World Health Organization African Region, N = 25,097. (Reprinted with permission from: Goodson JL, et al. Rubella epidemiology in Africa in the prevaccine era, 2002–2009. Journal of Infectious Diseases 2011. Suppl 1:S215–25.)
Figure 2
Figure 2. Distribution of countries using rubella vaccine in their routine immunization schedule in 2012 and countries planning introduction during 2013–2015
Figure 3
Figure 3. Transition from measles vaccine to combined measles-rubella vaccine Projected number to be vaccinated by year and vaccine, 2013–2u020
“SIA” is Supplemental Immunization Activity, usually a mass vaccination campaigns targeting persons in a wide age range regardless of prior vaccination status. “M” is measles vaccine alone while “MR” is combined Measles Rubella vaccine. Catch-up SIAs are first SIAs to boost overall population immunity. In measles, for example, most catch-up SIAs covered children 9 months through 14 years of age. Follow-up SIAs usually take place several years after the catch-up SIA and usually target a narrower age range, covering children born since the last SIA. For measles, this is usually 9 months through 4 years of age. Source: WHO/Expanded Programme on Immunization as at 1 December 2013. Information is subject to change based on country decisions on when to introduce rubella vaccine in the 194 WHO Member States.
Figure 4
Figure 4. Genetic influences on differences in rubella-induced immunity
Single nucleotide polymorphisms (SNPs) in receptors known to play a role in innate and antiviral immunity (cytokine/cytokine receptors, vitamin receptors, TLRs) are associated with measurable differences in humoral (antibody titers) and cellular (secreted cytokines) immunity after rubella vaccination. A number of HLA (Class I and Class II) alleles and haplotypes are also associated with differences in rubella-specific immunity. A hypothetical subject with a High Responder Genotype (CG SNP allele) represents a holistic compilation of SNPs discovered by interrogating polymorphisms present in candidate genes exhibits increased humoral and cellular responses to rubella vaccination. Low Responder Genotype, however, displays a hypo-immune phenotype to rubella vaccination and this may be influenced by multiple SNPs (TA SNP allele) in candidate genes. There are also unknown immunogenetic factors influencing immunity to rubella vaccine. These factors will be explored through Genome-wide association studies (GWAS), next-generation sequencing, and systems biology approaches.

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