K. C. College
Vaccinology currently practices administering the same set of vaccines universally with the underlying assumption that every individual will react in an immunologically similar way by the production of protective levels of antibodies, or cell-mediated immunity and almost no side effects. The assumption in mind is that the entire population is at the same risk level against the disease and that all will require the same vaccine dose/number of doses to develop immunity. Although having a major advantage such as, allowing widespread almost automatic delivery of vaccines, and as a result, the control of many infectious diseases it ignores individual variability in disease risk immunologic response, any genetic propensity for reactogenicity, and differences in dosage amount needed to generate immunity. Advances in immunology, genetics, molecular biology and bioinformatics have demonstrated the value of a personalized approach to therapeutic drug selection and dosing.
Precision vaccines just like precision medicine refer to ‘targeting’ vaccine antigens towards an augmented outcome i.e. maximum development of immunogenicity and minimizing the risk of either vaccine failure and side effects. Precision refers to either the individual level, the gender level, the racial/ethnic level or the subpopulation level. Recognizing these genetically encoded restrictions allow both informed clinical decision-making and opportunities to advance science by utilizing this information to develop better vaccines and enhanced vaccine administration algorithms.
The development of vaccinomics and personalized vaccinology was enabled by the completion of the first phase of the Human Genome Project and the first phase of the international HapMap and accelerated by new molecular assay tools that allow highthroughput detection of gene variations, particularly single nucleotide polymorphism (SNP) and linkage disequilibrium maps. More recently appreciated is the idea that polymorphisms in key immune response genes can lead to heterogeneity in immune responses to biologics
such as vaccines.
The science of vaccine has been advanced by vaccinomics immunogenetics by exhibiting the following:
- widespread polymorphism of immune response genes critical to the development of protective immune responses
- immunologically relevant outcomes related to these polymorphisms
- recognition of selective pressures to maintain and even enhance the type and number of immune response gene polymorphisms
- recognition that although gene polymorphisms throughout the pathway from infection through the development of immune responses are important, so far there seem to be few specific polymorphisms that are dominant determinants of the immune response (i.e., few ‘all or none’ polymorphisms) and
- immune response gene polymorphisms can have positive, negative or neutral effects on adaptive immune responses, and these polymorphisms explain individual variations in immune responses.
Theoretically, tailored vaccines are focused on complex associations of host genetic, environmental and other variables that affect immune responses to vaccines, the vaccine that is an ideal fit for a person. The creation of personalised vaccines is fundamentally a multi-step process, and we are at the start of the process. It is therefore important to establish correlations between differences in immune responses to vaccines and polymorphisms in genes with immune responses. Awareness of these associations may allow the design of a vaccine or adjuvant to circumvent immunogenetic constraints, and evidence of this theory is given by animal models.
Undertaking a detailed study and gathering a comprehensive working of how T cells recognize pathogenic antigens within the human leukocyte (HLA) system led to the emergence of personalized vaccines. The HLA complex includes the most polymorphic genes in the human genome with > 1000 HLA-A, -B and -C allelic variants already described. A stark decrease was observed in IgG antibody levels while an increase in cellular immune responses to both measles and mumps viral antigens when the HLA genes analysis led to identifying particular HLA haplotypes which were responsible for it.
The Human Genome Project has estimated that 1.42 million SNPs; are variations at a single site within a host’s DNA sequence; are the most frequent type of variation (90%); 60,000 SNPs falling in coding regions. Those falling within the coding regions are responsible for amino acid changes, such as nonsynonymous SNPs (change protein sequence), SNPs in regulatory regions, are likely to have the greatest impact on phenotype as they may have a direct effect on protein structure and function.
“Just as pharmacogenetics has suggested ways of designing drugs to minimize population variability, understanding mechanisms of immunogenetic variation may lead to new vaccines designed specifically to minimize immunogenetically based vaccine failure” was expressed by an investigator.
Thus, understanding and defining associations between key immune response gene polymorphisms and subsequent immune response can aid in designing new personalized vaccines.
Man differs in their response towards the vaccines and the immune response of the host varies within a population. Hence, it becomes exceedingly difficult to predict a reaction a specific person or a sub-population might have towards a particular vaccine. Thus, by identification and an all-embracing understanding of the associations between crucial immune response gene polymorphisms and subsequent immune response can be vital in design of personal vaccines.
A new era of vaccines is about to begin.