The use of transgenic and knockout mouse models is highly relevant to studying the role of a particular individual gene in specific immune responses
The use of transgenic and knockout mouse models is highly relevant to studying the role of a particular individual gene in specific immune responses. the risk of VAED, which are important to take into consideration, both in the assessment of vaccine safety and in finding ways to define models and immunization strategies that can alleviate such concerns. Keywords: vaccine, vaccine-associated enhanced disease, immunology, infectious diseases, Evodiamine (Isoevodiamine) immune response Introduction Vaccination is considered to be one of the most-cost effective medical interventions of Evodiamine (Isoevodiamine) the 20century (Praud et al., 2015; Ozawa et al., 2016; Leidner et al., 2019): The significant decrease in global morbidity and mortality associated with a Rabbit Polyclonal to Cytochrome P450 2A13 number of infections (Greenwood, 1645; Rappuoli et al., 2019) has synergized with the economic benefits in healthcare costs brought by the implementation of such preventive measures. Today, the goals of modern vaccinology in the context of infectious diseases are to: (A) create vaccines against (re)emerging diseases; (B) handle refractory pathogens for which efficient vaccines have proven difficult to develop, and (C) improve vaccination strategies, including vaccine accessibility (Greenwood, 1645; Centlivre and Combadire, 2015; Pollard and Bijker, 2020; Excler et al., 2021). Understanding and controlling the immune mechanisms elicited by such vaccines is crucial in moving forward in this quest. Beyond the fear of developing an ineffective vaccine, a concern (Graham, 2020) in the field of vaccinology is the formulation of vaccines that, upon subsequent natural contamination, may intensify the severity and worsen the prognosis of the pathology they were designed to protect against; a process known as a vaccine-associated enhanced disease (VAED) (Huisman et al., 2009; Jamrozik et al., 2021a; Munoz et al., 2021). More specifically, VAED is usually defined in this review as the immune-mediated aggravation of the clinical course of contamination following immunization relative to that in the absence of previous vaccination. VAED varies between vaccine platforms and may be caused by distinct mechanisms that are not yet completely comprehended or have not been Evodiamine (Isoevodiamine) entirely explored. Furthermore, to date, no factor has been shown to consistently predict the occurrence of VAED Evodiamine (Isoevodiamine) or even differentiate it from severe natural contamination. Also, it is likely that no single factor will be able to predict VAED risk, as it might be pathogen-dependent. In this article, we review the pathophysiological mechanisms that may lead to immune-mediated exacerbation of the disease. Then, we describe the preclinical and clinical cases in which VAED has been observed with vaccine candidates against diverse human and animal pathogens. Furthermore, we address the questions that were initially raised concerning the risk of VAED with anti-SARS-CoV-2 vaccines, as well as the extent to which it should be monitored. Finally, we discuss the use of preclinical and clinical models and how, in addition to vaccine formulation, they can be improved to better address safety in vaccine development. Describing pathophysiological pathways suspected to lead to vaccine-associated enhanced disease The purpose of vaccination is usually to induce a long-lasting immune response and/or immune memory that can be rapidly unleashed during a future encounter with the pathogen being vaccinated against (Pollard and Bijker, 2020). In certain circumstances, the immune responses brought on by exposure to antigens can, individually or through their association, favor exacerbated disease upon subsequent exposure to that same pathogen. Although this process has been described to occur naturally in the case of dengue virus (DENV) after sequential exposition to different serotypes (Halstead, 2007; Guzman et al., 2013), vaccination against most infectious diseases has resulted in only very rare cases of VAED (Huisman et al., 2009; Jamrozik et al., 2021a; Munoz et al., 2021). In the few reported cases, the enhanced disease was due to failed efforts of the immune system to control the infection and subsequently manifested with symptoms related to the organ(s) targeted by the virus. Thus, VAED Evodiamine (Isoevodiamine) generally presents as an exacerbation of the pathology seen in natural contamination and addressing VAED requires a proper understanding of the course of such an contamination and the host-pathogen interactions that take place. With the exception of the anti-DENV vaccine developed by Sanofi Pasteur and the FI-MV vaccine, which were withdrawn from the market, the occurrence of VAED has always been detected during preclinical and clinical experimental phases (i.e., before licensing) (Jamrozik et al., 2021a). However, continued safety monitoring is usually carried out even after marketing to ensure the benefits of the vaccines. While identifying VAED is crucial for the development of.