Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives

Abstract

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Patients with suspected allergic reactions to COVID‐19 vaccines can be safely revaccinated after diagnostic work‐up

“…Drug excipients are thought to be the major cause of anaphylaxis to vaccines 19–21 . Only six patients were positive in SPT or BaHR testing to the COVID‐19 vaccines and/or drug excipients:…”

“…Skin symptoms were predominant, and the majority of patients suffered from late onset reactions ranging from 6 h to several days after vaccination. The mechanism of delayed onset reactions in vaccines are poorly described, and most often, there is no recurrence of symptoms at revaccination 19–21 …”

Recent advances and developments in COVID‐19 in the context of allergic diseases

“…A few rare cases of anaphylaxis have been reported after vaccine administration 116‐119 . The scientific community has made great efforts to understand the immunopathological mechanisms underlying allergic reactions to COVID‐19 vaccines and their culprit component 120‐123 …”

“…The pathological mechanisms underlying allergic reactions are not fully understood. Several studies suggest an IgE‐mediated reaction, 121,126,127 whilst others have proposed a complement activation‐related pseudoallergy (CARPA) mediated by anaphylatoxins C3a and C5a together with anti‐PEG IgM and IgG antibodies induced by PEGyated nanobodies 121,127,128 . Mast cell release might be associated with hyperreactivity to the vaccine in children with cutaneous mastocytosis 127,129,130 .…”

“…Trometamol is added as a buffer in the Moderna vaccine and there has been a case report of anaphylaxis to this excipient in an intravenously administered radiocontrast agent 133 . Beta‐propiolactone (BPL), used to inactivate the virus, might induce an immune complex‐like reaction after vaccination, 121 which might cause an adverse reaction after a booster dose injection of the rabies human diploid cell vaccine 134,135 . Similar immunological mechanisms might be implicated in the adverse reactions associated with two widely used COVID‐19 vaccines in China, BBIBP‐CorV (Sinopharm) and Sinovac‐CoronaVac (Sinovac Life Sciences), which also contain BPL to inactivate SARS‐CoV‐2 121 …”