“Vaccines prime the human immune system (the body’s natural defenses) to defend and protect against a specific disease.”
Coronavirus disease (COVID-19) has overwhelmed the world with its devastating outcomes. The detection of new variants of severe acute respiratory coronavirus 2 (SARS-CoV-2) has further upraised global concerns. This, in turn, has altered the dynamics of the disease outbreak, contributing to the heterogeneous clinical behaviour of SARS-CoV-2. The reports show the majority of the infected patients (>85%) have mild symptoms or remain asymptomatic, while a few others exhibit aggressive life-threatening disease. These differences in disease severity could be attributed to various host genetic, environmental, and pathogen-related factors.
In order to curb the pandemic, vaccination is deemed to be a promising approach. Vaccines prime the human immune system (the body’s natural defenses) to defend and protect against a specific disease. Currently, universal vaccination is in practice with an assumption that the immune response to vaccines amongst all the individuals is identical. However, there seems to be a substantial variation in immune response between the individuals/subgroups of the population. For example, sub-optimal immune responses are noted in the elderly population and infants due to aging or immature immune systems. Likewise, post-vaccination, women display superior immune responses with a higher propensity for adverse reactions than men. Thus, given the complexity and diversity of the human immune system and the host genome, the conventional ‘one-size-fits-all’ vaccination approach could be inapt, thereby creating a need for alternative vaccination strategies.
Personalised vaccination, a newly evolving approach has emerged as a better alternative to the conventional approach. Here, the vaccines are administered based on the individual or subgroup characteristics of the population, by taking into account the influence of genetic and non-genetic factors on the immune response to vaccines. Further, given the heterogeneous nature of SARS-CoV-2, the development of COVID-19 vaccines through personalised vaccination approach could prove advantageous. On this front, this article aims to provide an overview of personalised vaccination and its relevance to COVID-19 vaccines.
“Personalised vaccination could also provide early insights on patho-physiological mechanisms of infectious diseases like COVID-19.”
Personalised vaccines target a particular vaccine antigen to produce an optimal immune response. The study of personalised vaccination strategies is referred to as ‘personalised vaccinology’, comprising of two terminologies namely ‘vaccinomics’ and ‘adversomics’. In ‘vaccinomics’, the influence of genetic and non-genetic factors on the heterogeneity of immune response to vaccines are studied. On the other hand, ‘adversomics’ provides a scientific basis to understand the mechanisms of vaccine induced adverse reactions.
Through this, a new methodology of vaccine development paradigm “discover-validate characterize-apply” is established. Here, first, the genetic variants associated with immune responses, and the host-pathogen interaction mechanisms are discovered using high dimensional bioinformatic approaches. Second, the discovered findings are replicated and validated in the subgroups of interest. Third, the functional studies of well-defined genetic variants are performed to characterise and determine the variations in the immune response. Lastly, these characteristics are applied to predict beneficial/adverse immune responses, and to develop new vaccines. Thus, the above paradigm forms an iterative process, wherein, new developments enhance scientific understanding and lead to novel breakthroughs.
Application of personalised vaccination can offer multitude benefits:
- Individualised vaccination approach – the type of vaccines, dosage, and timeline of vaccination could be tailored to individuals/subgroups of population.
- Predict the likelihood of beneficial or adverse immune response to vaccines.
- Aid in the design of new vaccines based on the specific genotype or mutant variants.
Furthermore, personalised vaccination could also provide early insights on patho-physiological mechanisms of infectious diseases like COVID-19, which in turn, helps in early identification, diagnosis and prevention of such disease outbreaks.
“Post-vaccination with COVID-19 vaccines, cases of unusual blood clots are seen mainly in women under 60 years of age. “
Relevance of personalised vaccination to COVID-19 vaccine development
The unprecedented COVID-19 global outbreak triggered a pressing need to develop novel vaccines within a short timeline. As a result, we now have 17 different COVID-19 vaccines approved by at least one national regulatory authority. Till now, these vaccines have proven to be effective with acceptable levels of safety in the general population. However, amongst the vaccinated individuals, significant concerns do exist over the varied immune responses. This could be due to the differential role of various host, genetic and environmental factors as described below.
A collaborative study ‘COVID-19 host genetics initiative’ elucidated the role of host genetic factors, and determined 15 genetic loci to be strongly associated with COVID-19 susceptibility/ severity. In addition, a comparative genetic analysis of the SARS-CoV-2 binding receptor angiotensin converting enzyme-2 (ACE-2), reveals increased ACE-2 expression/function in the East Asian population compared to South Asians. These observations unfold the genetic predilection of an individual/subgroup population towards differential susceptibility to COVID-19.
Furthermore, the extant literature shows gender related differences in immune response with higher COVID-19 severities and fatalities in men than women. However, post-vaccination with COVID-19 vaccines, cases of unusual blood clots are seen mainly in women under 60 years of age. Besides, smoking, body mass index, pre-existing immunity, co-morbidities like Human Immunodeficiency Virus (HIV), cancer, etc can also affect the immune responses. Hence, owing to these heterogeneous immune responses, personalised vaccination strategies could be of profound importance to the development of COVID-19 vaccines. Also, the detailed assessment of the characteristics of the individual immune responses guide in the appropriate design of personalised vaccines.
Personalised COVID-19 vaccines: preliminary studies
Few preliminary studies of personalised vaccination strategies to COVID-19 vaccines show promising results. ‘AV-COVID-19’, a personalized vaccine candidate, developed using an autologous cell therapy platform has passed pre-clinical and phase 1 vaccine trials. Here, the vaccine is prepared from the extracted autologous immune cells and is primed with multiple SARS-CoV-2 spike antigens. These are then re-administered to the same individual to develop specific rapid immune responses. This offers two unique advantages over traditional vaccines. First, the vaccine ingredients are available in the form of ready kits, which in turn, helps in local manufacturing of vaccines. Second, the modification of antigens in ready kits aid in the rapid development of vaccines to target new mutant variants. Thus, through this cost-effective personalised model, precise and rapid immune responses to both existing and new variants could be achieved.
Another illustration of personalised vaccination strategy is via ‘age-personalized-dosing’, experimented with the Moderna vaccine. In general, compared to the younger population, the elderly have lower immunity, and are at high risk of COVID-19 fatalities. However, social interaction seems to be higher amongst the younger with increased rate of COVID-19 transmission. By adapting the ‘age-personalized-dosing’ approach, both the mortality and transmission rates were reduced through vaccination of the elderly population at full dose and younger at a quarter dose, which proved to be beneficial. Thus, deploying personalised vaccination strategies optimize individual/subgroup specific immune responses against COVID-19.
The prevailing COVID-19 pandemic commands a decisive action to prevent the rampant spread of infection and deaths. Although vaccination is the key to overcoming the crippling effects of the pandemic, varying immune responses to vaccination through the conventional one-size-fits-all approach is still a concern. On the contrary, personalized vaccination helps to predict the immune responses considering the unique characteristics of an individual/the population subgroups. Overall, personalized vaccination approach enables effective management of the ongoing pandemic, mitigating the impact of the mutant strains.
“Dr. Shruthi K.Venugopalareddy is a medical doctor with a master’s degree in clinical pharmacology. She presently works as an Associate Medical Safety Director (Pharmacovigilance Department) at IQVIA, Sweden. Her interests mainly focus on applied research with an emphasis on patient safety.”