Variability in vaccine efficacy
Natural selection in a Bangladeshi Population from the cholera-endemic Ganges-river delta: Two independent questions with similar answers from two studies.
Currently available vaccines against various infections do not elicit similar levels of immune response in individuals receiving them. In a study on a cholera vaccine, Partho Majumder and his colleagues have found genetic variants that are associated with immune response. Interestingly, this study also found an innate immunity gene to be associated with vaccine response. Their study will soon be published in the European Journal of Human Genetics, but is already available online here on the journal’s web site.
Partho Mazumder is a leading human geneticist who heads the National Institute of Biomedical Genomics. We discussed a recent news item in The Hindu, by email. Here’s the original article in Science Translational Medicine . Here’s what Partha has to say on this important paper:
Partho says: “Till a few years ago, diseases were classified as being due to two separate sets of causes, genetic and environmental. Infectious diseases were provided as examples of “environmental diseases.” With the ability to carry out genetic studies spanning the entire human genome, it has become clear that genetic variations in the host modulate susceptibility to infectious diseases. This paper on cholera-susceptibility is an excellent example. This paper is interesting not only because of its significant conclusions pertaining to susceptibility to a deadly infectious agent, Vibrio cholerae, but also because of its innovative use of population genetic and statistical methods. The investigators reasoned that individuals who had the genetic ability to escape the attacks of Vibrio cholerae in spite of living in a cholera-endemic region must have gained a selective advantage. Therefore, if one is able to identify the regions of the genome that confer such selective advantage in a cholera-endemic region – such as, Bangladesh, it may be possible to identify genes that confer resistance to cholera. The authors did just this; they first identified genomic regions that have evolved under strong selective pressures, then they identified some variants in genes and genetic pathways that were associated with resistance to cholera, which they validated in an independent sample. They found that variants in the innate immune signaling pathways, which are responsible for recognizing the pathogen, are primarily associated with cholera-resistance. Some other genes that are highly expressed in the digestive tract were also found to be associated with resistance.
Understanding biological mechanisms underlying resistance to infectious diseases are a key to vaccine development. The findings of this study are a major step in that direction.”