THE GENETIC BASIS FOR INTERINDIVIDUAL IMMUNE RESPONSE VARIATION TO MEASLES VACCINE: NEW UNDERSTANDING AND NEW VACCINE APPROACHES

Monday, 14th of April 2014

[source]Expert Review of Vaccines[|source]

Although effective, the current live-attenuated measles vaccines have limitations. Vaccine failure (i.e., the failure for the individual to either mount or sustain a protective immune response) occurs despite the receipt of two doses of vaccine. As a result, even in highly vaccinated populations, substantial proportions of those infected in an outbreak will have been previously vaccinated. This phenomenon raises strategic challenges, including the need for research on determinants of measles vaccine response, and the development of improved measles vaccines.

 

Of the various genes linked to vaccine-induced immune responses, HLA genes have been intensely studied and perhaps have the highest impact on immunity. Antigen processing and presentation by HLA class I and class II molecules contributes to antigen-specific immune response. Hence, polymorphisms in the HLA and other genes are a possible explanation for interindividual variations in vaccine-induced immune outcomes. Population-based studies have found specific HLA allelic associations, including haplotypes and supertypes, with measles vaccine-induced adaptive humoral and cellular immune responses after one or two doses of vaccine

 

In this review report, the authors summarize recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. The report concludes by proposing a paradigm shift in measles vaccine development from the empiric Isolate → Inactivate/Attenuate → Inject model to Discover → Replicate → Validate → Apply – a novel model that utilizes genome-based techniques. More details are available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570049/

 

ABSTRACT

The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of vaccinomics for novel vaccine development.