The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches

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.

Keywords::

• adaptive immunity
• genetic association studies
• human leukocyte antigens
• immunogenetics
• measles vaccine
• single nucleotide polymorphisms

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the NIH.

Financial & competing interests disclosure

Funding support was provided by NIH grants AI33144, AI48793 (which recently received a MERIT Award) from the National Institute of Allergy and Infectious Diseases. GA Poland and IG Ovsyannikova hold patents for the discovery of novel measles peptides potentially useful in developing new diagnostic assays and vaccines. GA Poland is the chair of a Safety Evaluation Committee for investigational nonmeasles vaccine trials being conducted by Merck Research Laboratories. RM Jacobson is a member of a safety review committee for a post-licensure study funded by Merck & Co. concerning the safety of a licensed human papillomavirus vaccine. He is also a member of a data monitoring committee for an investigational vaccine trial funded by Merck & Co. 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. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.