Vaccines are among the greatest and most cost-effective accomplishments of modern medicine. During vaccine research and development (R&D) i.e. preclinical and clinical testing, any potential adverse events following immunization (AEFI) are actively sought, followed up and documented. Moreover, active post-marketing surveillance is required to provide sufficient statistical power to detect rare AEFI.

The requirements for vaccines are two-fold. On one hand, vaccines should induce a protective immunological response. On the other hand, any form of toxicity to the host should be minimized. An immune response inducing an AEFI may either be due to the immediate immunological response to the vaccine or the result of indirect or unintended adverse effects that may or may not involve the immune system directly.

Safety studies during the discovery and early preclinical phases of vaccine (and drug) development have traditionally been focused on immediate (for example, cyto-) toxicity. In the meantime, it has become clear that specific immunological biomarkers may be able to predict AEFI early stages of vaccine development. For instance, significant systemic increases in IL-1β and IL-6 may cause inflammation with an ensuing fever, which, if sustained, is considered a severe systemic adverse event. Furthermore, increases in serum or plasma acute-phase proteins, such as C-reactive protein, may be linked to inflammation.

Modern vaccine discovery and development has placed major emphasis on innate pro-inflammatory responses. However, there is a strong indication that such inflammatory responses, which may result in untoward clinical adverse events, are not always required for vaccines to be efficacious. Indeed, beyond a certain threshold, overbearing immune responses may not only be superfluous but harmful if sustained. As such, a further systematic approach to detect the clinical signs and symptoms of immunologic/inflammatory AEFI are required.

The future of vaccine discovery and development will likely involve a systems biology approach, encompassing the immune, nervous, metabolic, digestive, and microbiome systems of the host. Therefore, new attempts to designing vaccines should involve a holistic -systems-biology approach rather than being based on specific organ toxicities. A systems approach will recognize that various biological systems are working in tandem to produce a balanced and healthy individual.

In this special issue, we welcome authors to submit Original Research, Review, Clinical Trial, and Perspective articles addressing the issue of vaccine safety from an immunological perspective, including:

a. AEFI affecting either the immune system or non-immune systems,
b. Novel clinical vaccine safety monitoring systems,
c. Biomarkers of vaccine safety in preclinical models,
d. Novel findings of biological factors linked to vaccine safety that influence the immune system,
e. Sex/gender differences in immune responses and adverse events to vaccines in preclinical or clinical studies,
f. Novel approaches to balance vaccine efficacy and safety by addressing increased pro-inflammatory immune responses and their effects on other biological systems.

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Frontiers in Immunology

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