Field of Science

#vaccines - can you predict how well they'll work?

 
Vaccines are great aren't they -  they offer us probably the most cost-effective means of reducing death and suffering on a worldwide scale that extends to both humans and other animals. The problem is that it's never been as easy as just dreaming up a vaccine for the latest virus to afflict us. Effective vaccines are extremely difficult to produce, even for the most well-researched pathogens and, even when you do develop one, plow billions into it's generation and testing, and get it successfully through all the necessary clinical trials it still might not work so perfectly. 


This sheer deadly annoyance is known as vaccine failure - and it's a massive problem if you're interested in eradicating infectious diseases, which of course many of us are. For some info, see what's been happening with the elimination of mumps - some people, even those who have been vaccinated with the MMR twice, are getting the disease. If we can't eradicate diseases like measles and mumps - which have an amazingly good vaccine - how ever can we eliminate more difficult-to-handle viruses like HIV?

This all has encouraged a major research area has sprung up in lessening the effects of vaccine failure on immunisation campaigns through attempting to predict those that will respond well and those who won't and potentially focusing your attention on the ones who won't respond. And this research may even teach us something about immunology through highlighting those critical genes required for antiviral defence and this could be used in the de novo design of vaccines in the future.

There are all sorts of types of vaccine failure: it may be the virus differs in some crucial antigenic site when compared to your vaccine, the vaccine may work superbly initially but 10 years later the very same immunity could wane. But, one of the main types of this - and probably the most important - is the failure of a patient (someone receiving the vaccine) to mount the desired immune response: no antibodies, no T cells etc. This means that despite having been vaccinated, they will still get infected and pass the virus on. In some cases this can extend to 10% of people being immunised - even with highly successful vaccines like the MMR. Scary when you think that many of these highly infectious viruses require nearly 90% of the population to be immune before it can no longer spread.

If we rule out differences in the vaccine people get - which I don't think we can do easily as differences in strains used, storage temperatures, administration could change between patients - but you can try, you are left with differences in the people. These differences could be things like age at vaccination, previous infection history, stress levels - anything that can influence your immune system (which is a lot of things!). But, a major contributory factor you would predict to be is their genetics: the inter-personal differences in DNA sequence, which is especially true when you consider the range of proteins a vaccine requires to interact with to induce immunnity in any given person - genetic variation between the coding or non-coding squences of each of these proteins may change how well they respond a given vaccine.

A basic outline of part of the innate sensing of viruses - how may genetic variation in these components influence vaccine responses? http://www.nature.com/ng/journal/v38/n8/images/ng0806-866-F1.jpg

Much of this research is carried out by guys over at the Mayo Clinic Vaccine research group through Gregory Poland who, using standard genotypying methods, uncover a few statistically significant associations between SNPs and the immune response to particular vaccines: measles, rubella and smalllpox, for example. But of course this can and should be extended to other viruses, pathogens and the like. Have a look at some of their research carried out over the last few years:

Maybe your proteins don't 'see' the vaccine as well:

Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine.

2'-5'-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine.

Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results.

Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine.

Maybe your immune system doesn't respond like we hoped:

Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.

Associations between cytokine/cytokine receptor single nucleotide polymorphisms and humoral immunity to measles, mumps and rubella in a Somali population.

Maybe, when using live vaccines such as the MMR, those vaccine viruses don't replicate as efficiently as they should because of receptor changes:

Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors.

I predict that in the future they will extend their studies to bigger population sizes and to different races but once they have figured out what variations are the most important I will be interested in how this will be used in vaccination efforts across the world and how it will influence how we immunise. For example, how will the already cash-strapped vaccination efforts in sub-Saharan Africa and South-East Asia cope with using these tests? Or will it be just used in developed world clinics? Also, this work fits nicely into the systems biology efforts which also aims to understand - and predict - the human response to vaccination with the goal of generating improved vaccines (see post here).



ResearchBlogging.orgHaralambieva IH, Ovsyannikova IG, Umlauf BJ, Vierkant RA, Shane Pankratz V, Jacobson RM, & Poland GA (2011). Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine. Vaccine PMID: 21939710

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