Vaccinomics and adversomics: key elements for a personalized vaccinology.

Vaccines are one of the most important and effective tools in the prevention of infectious diseases and research about all the aspects of vaccinology are essential to increase the number of available vaccines more and more safe and effective. Despite the unquestionable value of vaccinations, vaccine hesitancy has spread worldwide compromising the success of vaccinations. Currently, the main purpose of vaccination campaigns is the immunization of whole populations with the same vaccine formulations and schedules for all individuals. A personalized vaccinology approach could improve modern vaccinology counteracting vaccine hesitancy and giving great benefits for human health. This ambitious purpose would be possible by facing and deepening the areas of vaccinomics and adversomics, two innovative areas of study investigating the role of a series of variables able to influence the immune response to vaccinations and the development of serious side effects, respectively. We reviewed the recent scientific knowledge about these innovative sciences focusing on genetic and non-genetic basis involved in the individual response to vaccines in terms of both immune response and side effects.

Metabolomic Signatures Differentiate Immune Responses in Avian Influenza Vaccine Recipients.

BACKGROUND: Avian influenza viruses pose significant risk to human health. Vaccines targeting the hemagglutinin of these viruses are poorly immunogenic without the use of adjuvants. METHODS: Twenty healthy men and women (18-49 years of age) were randomized to receive two doses of inactivated influenza A/H5N1 vaccine alone (IIV) or with AS03 adjuvant (IIV-AS03) one month apart. Urine and serum samples were collected on day 0 and on days 1, 3, and 7 following first vaccination and subjected to metabolomics analyses to identify metabolites, metabolic pathways, and metabolite clusters associated with immunization. RESULTS: Seventy-three differentially abundant (DA) serum and 88 urine metabolites were identified for any post-vaccination day comparison. Pathway analysis revealed enrichment of tryptophan, tyrosine and nicotinate metabolism in urine and serum among IIV-AS03 recipients. Increased urine abundance of 4-vinylphenol sulfate on Day 1 was associated with serologic response based on hemagglutination inhibition responses. In addition, 9 DA urine metabolites were identified in participants with malaise compared to those without. CONCLUSIONS: Our findings suggest that tryptophan, tyrosine, and nicotinate metabolism are upregulated among IIV-AS03 recipients compared with IIV alone. Metabolites within these pathways may serve as measures of immunogenicity and may provide mechanistic insights for adjuvanted vaccines.

Relapsing myocarditis following initial recovery of post COVID-19 vaccination in two adolescent males - Case reports.

Whilst there has been significant public health benefits associated with global use of COVID-19 spike protein vaccines, potential serious adverse events following immunization have been reported. Acute myocarditis is a rare complication of COVID19 vaccines and often it is self-limiting. We describe two cases experiencing recurrent myocarditis following mRNA COVID-19 vaccine despite a prior episode with full clinical recovery. Between September 2021-September 2022 we observed two male adolescents with recurrent myocarditis related to mRNA-based-COVID19 vaccine. During the first episode both patients presented with fever and chest pain few days after their second dose of BNT162b2 mRNA Covid-19 Vaccine (Comirnaty®). The blood exams showed increased cardiac enzymes. In addition, complete viral panel was run, showing HHV7 positivity in a single case. The left ventricular ejection fraction (LVEF) was normal at echocardiogram but cardiac magnetic resonance scanning (CMR) was consistent with myocarditis. They were treated with supportive treatment with full recovery. The 6 months follow-up demonstrated good clinical conditions with normal cardiological findings. The CMR showed persistent lesions in left ventricle 's wall with LGE. After some months the patients presented at emergency department with fever and chest pain and increased cardiac enzymes. No decreased LVEF was observed. The CMR showed new focal areas of edema in the first case report and stable lesions in the second one. They reached full recovery with normalization of cardiac enzymes after few days. These case reports outline the need of strict follow-up in patients with CMR consistent with myocarditis after mRNA-based-COVID19 vaccine. More efforts are necessary to depict the underlying mechanisms of myocarditis after SARS-CoV2 vaccination to understand the risk of relapsing and the long-term sequelae.

Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system. ACE2 is present as membrane-bound on several cell types, including the mucosa of the upper respiratory and of the gastrointestinal tracts, the endothelium, the platelets, and in soluble form in the plasma. The ACE2 enzyme converts the vasoconstrictor angiotensin II into peptides with vasodilator properties. Here we review the pathways for immunization and the molecular mechanisms through which the Spike protein, either from SARS-CoV-2 or encoded by the mRNA-based vaccines, interferes with the Renin-Angiotensin-System governed by ACE2, thus altering the homeostasis of the circulation and of the cardiovascular system. Understanding the molecular interactions of the Spike protein with ACE2 and the consequent impact on cardiovascular system homeostasis will direct the diagnosis and therapy of the vaccine-related adverse effects and provide information for development of a personalized vaccination that considers pathophysiological conditions predisposing to such adverse events.

Will Omics Biotechnologies Save Us from Future Pandemics? Lessons from COVID-19 for Vaccinomics and Adversomics.

The COVID-19 pandemic had cross-cutting impacts on planetary health, quotidian life, and society. Mass vaccination with the current gene-based vaccines has helped control the pandemic but unfortunately it has not shown effectiveness in preventing the spread of the virus. In addition, not all individuals respond to these vaccines, while others develop adverse reactions that cannot be neglected. It is also a fact that some individuals are more susceptible to infection while others develop effective immunization post-infection. We note here that the person-to-person and population variations in vaccine efficacy and side effects have been studied in the field of vaccinomics long before the COVID-19 pandemic. Additionally, the field of adversomics examines the mechanisms of individual differences in the side effects of health interventions. In this review, we discuss the potential of a multi-omics approach for comprehensive profiling of the benefit/risk ratios of vaccines. Vaccinomics and adversomics stand to benefit planetary health and contribute to the prevention of future pandemics in the 21st century by offering precision guidance to clinical trials as well as promoting precision use of vaccines in ways that proactively respond to individual and population differences in their efficacy and safety. This vision of pandemic prevention based on personalized instead of mass vaccination also calls for equity in access to precision vaccines and diagnostics that support a vision and practice of vaccinomics and adversomics in planetary health.

Vaccinomics: a cross-sectional survey of public values.

Objective: We characterize public values regarding vaccinomics, which aims to improve vaccine safety and effectiveness using genomics.Methods: Panel survey (2020) of ≥18-year-olds with embedded animation introduced vaccinomics. Sociodemographic, health, and vaccination-related items were adapted from validated scales. Novel items measured trust in public health authorities, vaccinomics-related values, and preferences for federal funding: vaccinomics compared with vaccine issues and chronic diseases. Beginning and end of survey confidence in vaccine safety was measured to assess potential changes. Data were weighted to the U.S. Census. Vaccinomics-related concerns were stratified by sociodemographic characteristics, vaccine hesitancy status (composite outcome), reported serious vaccine reactions, and trust in public health authorities (PHA). Log binomial regression models estimated associations between these variables and agency to make vaccine-related decisions.Results: Most (70.7%, N = 1,925) respondents expected vaccinomics would increase their vaccine confidence compared to now. Agreement was highest among those without serious vaccine reaction experience (unexperienced: 74.2% versus experienced: 62.3%), with high trust in PHA (high: 83.3% versus low: 57.4%), and low vaccine hesitancy among parents of teenagers (low: 78.8% versus high: 62.5%) and adults without minor children (low: 79.8% versus high: 60.6%; all p < .01). Belief that vaccination was an individual's choice was associated with reported serious reactions (adjusted Prevalence Ratio (aPR): 1.16; 95% CI: 1.07, 1.25) and low trust (aPR: 0.91; 0.84, 0.98). Beginning versus end of survey vaccine safety perceptions were similar.Conclusion: Federal funding, communications, and policies should assure the public that vaccinomics will not remove their decision-making power and engender trust in PHA.

Vaccinomics and Adversomics in the Era of Precision Medicine: A Review Based on HBV, MMR, HPV, and COVID-19 Vaccines.

Precision medicine approaches based on pharmacogenomics are now being successfully implemented to enable physicians to predict more efficient treatments and prevention strategies for a given disease based on the genetic background of the patient. This approach has already been proposed for vaccines, but research is lagging behind the needs of society, and precision medicine is far from being implemented here. While vaccinomics concerns the effectiveness of vaccines, adversomics concerns their side effects. This area has great potential to address public concerns about vaccine safety and to promote increased public confidence, higher vaccination rates, and fewer serious adverse events in genetically predisposed individuals. The aim here is to explore the contemporary scientific literature related to the vaccinomic and adversomic aspects of the three most-controversial vaccines: those against hepatitis B, against measles, mumps, and rubella, and against human Papilloma virus. We provide detailed information on the genes that encode human leukocyte antigen, cytokines and their receptors, and transcription factors and regulators associated with the efficacy and safety of the Hepatitis B and Measles, Mumps and Rubella virus vaccines. We also investigate the future prospects of vaccinomics and adversomics of a COVID-19 vaccine, which might represent the fastest development of a vaccine ever.

Vaccinomics, adversomics, and the immune response network theory: individualized vaccinology in the 21st century.

Vaccines, like drugs and medical procedures, are increasingly amenable to individualization or personalization, often based on novel data resulting from high throughput "omics" technologies. As a result of these technologies, 21st century vaccinology will increasingly see the abandonment of a "one size fits all" approach to vaccine dosing and delivery, as well as the abandonment of the empiric "isolate-inactivate-inject" paradigm for vaccine development. In this review, we discuss the immune response network theory and its application to the new field of vaccinomics and adversomics, and illustrate how vaccinomics can lead to new vaccine candidates, new understandings of how vaccines stimulate immune responses, new biomarkers for vaccine response, and facilitate the understanding of what genetic and other factors might be responsible for rare side effects due to vaccines. Perhaps most exciting will be the ability, at a systems biology level, to integrate increasingly complex high throughput data into descriptive and predictive equations for immune responses to vaccines. Herein, we discuss the above with a view toward the future of vaccinology.