When Vaccinations are Challenging: From Immune Diseases to Hypersensitivity Reactions

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Clinical Immunology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 68162

Special Issue Editor


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Guest Editor
Department of Medicine, University of Verona, Verona University Hospital, 37134 Verona, Italy
Interests: allergy and clinical immunology; bronchial asthma; severe asthma; immunodeficiencies; biologic drugs
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Special Issue Information

Dear Colleagues,

Although vaccines have been part of physicians’ practice for many years and represent the most successful prevention strategy for communicable diseases, some challenges still characterize their daily use and applicability. In fact, vaccines have been recently proposed as part of the management of some peculiar conditions, such as immune diseases, particularly immunodeficiency, chronic respiratory diseases or bronchiectasis, and autoimmune diseases treated with immunosuppressant drugs. The expected outcomes, as well as their use in specific phenotypes, have not been completely clarified.

Further, risk assessment, prevention, and management of hypersensitivity reactions to vaccines still present some controversial aspects.

This Vaccines Special Issue aims at addressing the above-mentioned challenges and unmet needs through reviews and research contributions, including original articles and case series/reports.

Dr. Marco Caminati
Guest Editor

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Keywords

  • Vaccines hypersensitivity
  • Vaccines and chronic conditions
  • Vaccines and chronic respiratory diseases
  • Vaccines and immune diseases
  • Vaccines and immunosuppressant drugs

Published Papers (10 papers)

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Editorial

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3 pages, 173 KiB  
Editorial
Who Is Really at Risk for Anaphylaxis Due to COVID-19 Vaccine?
by Marco Caminati, Gabriella Guarnieri and Gianenrico Senna
Vaccines 2021, 9(1), 38; https://doi.org/10.3390/vaccines9010038 - 11 Jan 2021
Cited by 19 | Viewed by 6399
Abstract
The vaccination campaign against the Severe acute respiratory syndrome coronavirus 2 (Sars-Cov-2) started on 8 December 2020 in UK, after the approval of BNT162b2 by the Healthcare products Regulatory Agency (MHRA) [...] Full article

Research

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11 pages, 241 KiB  
Article
Uptake of Vaccinations among Children with Chronic Diseases Is Affected by Knowledge Gaps and Implementation Challenges in Italy
by Alessandra Beni, Sara Mazzilli, Elisabetta Bellino, Giorgio Costagliola, Elena Ferretti, Pier Luigi Lopalco, Lara Tavoschi and Diego Giampietro Peroni
Vaccines 2021, 9(11), 1217; https://doi.org/10.3390/vaccines9111217 - 20 Oct 2021
Cited by 5 | Viewed by 1541
Abstract
(1) Background: Children with chronic medical conditions may be at increased risk for severe complications related to vaccine-preventable infections. Therefore, additional booster doses or supplementary vaccines are recommended, over and above the routine immunization schedule for healthy children. The aim of this study [...] Read more.
(1) Background: Children with chronic medical conditions may be at increased risk for severe complications related to vaccine-preventable infections. Therefore, additional booster doses or supplementary vaccines are recommended, over and above the routine immunization schedule for healthy children. The aim of this study was to investigate attitude, knowledge, and practices toward additional vaccinations for children affected by chronic conditions among pediatricians and parents. (2) Methods: This study is based on two surveys: (i) a national cross-sectional survey, targeting pediatrician working in hospitals or in the primary health sector; (ii) a local cross-sectional survey, targeting parents of children with a previous diagnosis of chronic disease. (3) Results: Despite the fact that most of the health professionals and parents interviewed had an overall positive vaccine attitude, most pediatricians did not show an adequate knowledge of additional vaccinations for children affected by chronic diseases. Moreover, the coverage of additional recommended vaccinations in chronic pediatric patients was low. (4) Conclusions: This research highlighted important existing challenges hampering optimal vaccination coverage among pediatric chronic patients, including knowledge gaps on tailored vaccination schedules among pediatricians and organizational issues. The ongoing review of the Italian national immunization plan is a not-to-be-missed-opportunity to include evidence-based, detailed, and comprehensive recommendations on vaccinations for children affected by chronic conditions. Full article
8 pages, 2151 KiB  
Article
COVID-19 Vaccination in Patients with Severe Asthma on Biologic Treatment: Safety, Tolerability, and Impact on Disease Control
by Marco Caminati, Gabriella Guarnieri, Veronica Batani, Elena Scarpieri, Anita Finocchiaro, Fulvia Chieco-Bianchi, Gianenrico Senna and Andrea Vianello
Vaccines 2021, 9(8), 853; https://doi.org/10.3390/vaccines9080853 - 4 Aug 2021
Cited by 21 | Viewed by 4489
Abstract
Background: COVID-19 vaccination has been recommended for severe asthmatics. We aimed to evaluate the safety, tolerability, and impact on disease control and patient’s quality of life of the mRNA SARS-CoV-2/COVID-19 vaccine in severe asthma patients regarding biologic treatment. Methods: Severe asthmatic patients regularly [...] Read more.
Background: COVID-19 vaccination has been recommended for severe asthmatics. We aimed to evaluate the safety, tolerability, and impact on disease control and patient’s quality of life of the mRNA SARS-CoV-2/COVID-19 vaccine in severe asthma patients regarding biologic treatment. Methods: Severe asthmatic patients regularly managed by two big allergy and respiratory referral centers were offered to undergo Pfizer COVID 19 vaccination at the hospital site. Patients filled in an adverse events questionnaire after the first and second dose, as well as the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ). Results: Overall, 253 patients were vaccinated; only 16 patients refused. No serious events were detected. Less than 20% of patients reported side effects, most of which were classified as very common side effects. No differences were reported according to the ongoing biologic drug. A significant improvement in both ACT and AQLQ was observed between the first and the second dose administration. Conclusions: Our data confirm the optimal safety and tolerability profile of mRNA SARS- CoV-2/COVID-19 in severe asthma patients on biologic treatment, as well as their positive attitude towards COVID-19 vaccination. The negligible proportion of patients reporting side effects and the absence of asthma exacerbations are relevant to support the COVID-19 vaccination campaign in severe asthma patients worldwide. Full article
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Review

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15 pages, 315 KiB  
Review
Vaccinations and Autoimmune Diseases
by Bianca Olivieri, Corrado Betterle and Giovanna Zanoni
Vaccines 2021, 9(8), 815; https://doi.org/10.3390/vaccines9080815 - 22 Jul 2021
Cited by 55 | Viewed by 8056
Abstract
Vaccines represent one of the most effective measures of public health medicine, saving countless lives and preventing lifelong disabilities. Vaccines are extremely safe, however, no vaccine is completely free from risks and adverse events can occur following vaccination. An adverse event following immunization [...] Read more.
Vaccines represent one of the most effective measures of public health medicine, saving countless lives and preventing lifelong disabilities. Vaccines are extremely safe, however, no vaccine is completely free from risks and adverse events can occur following vaccination. An adverse event following immunization (AEFI) may be a true adverse reaction caused by the vaccine or an event that temporally occurred after immunization but is not caused by it. Among the adverse reactions to vaccines, one of the most feared is the triggering of autoimmune diseases, which are a heterogeneous group of disorders characterized by dysregulation of the immune system. Currently, no mechanisms have been demonstrated that could explain the correlation between vaccination and the development of autoimmune diseases. Furthermore, epidemiological studies do not support the hypothesis that vaccines cause systemic autoimmune diseases. The only confirmed associations, although very rare, are those between the flu vaccine and Guillain-Barré syndrome, especially with old vaccine preparations, and measles-mumps-rubella (MMR) vaccine and thrombocytopenia. Due to the SARS-CoV2 pandemic, new types of vaccines have been developed and are now available. Close vaccine safety-surveillance is currently underway for these new vaccines. Full article
9 pages, 458 KiB  
Review
Probiotics as Adjuvants in Vaccine Strategy: Is There More Room for Improvement?
by Diego Giampietro Peroni and Lorenzo Morelli
Vaccines 2021, 9(8), 811; https://doi.org/10.3390/vaccines9080811 - 21 Jul 2021
Cited by 15 | Viewed by 4310
Abstract
Background. It has been recognized that microbiota plays a key role in shaping immune system maturation and activity. Since probiotic administration influences the microbiota composition and acts as a biological response modifier, the efficacy of an adjuvant for boosting vaccine-specific immunity is investigated. [...] Read more.
Background. It has been recognized that microbiota plays a key role in shaping immune system maturation and activity. Since probiotic administration influences the microbiota composition and acts as a biological response modifier, the efficacy of an adjuvant for boosting vaccine-specific immunity is investigated. Methods. A review of the literature was performed, starting from the mechanisms to laboratory and clinical evidence. Results. The mechanisms, and in vitro and animal models provide biological plausibility for microbiota use. Probiotics have been investigated as adjuvants in farm conditions and as models to understand their potential in human vaccinations with promising results. In human studies, although probiotics were effective in ameliorating seroconversion to vaccines for influenza, rotavirus and other micro-organisms, the results for clinical use are still controversial, especially in particular settings, such as during the last trimester of pregnancy. Conclusion. Although this topic remains controversial, the use of probiotics as adjuvant factors in vaccination represents a strategic key for different applications. The available data are deeply influenced by heterogeneity among studies in terms of strains, timing and duration of administration, and patients. Although these do not allow us to draw definitive conclusions, probiotics as adjuvants in vaccination should be considered in future studies, especially in the elderly and in children, where vaccine effectiveness and duration of immunization really matter. Full article
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8 pages, 244 KiB  
Review
Vaccination in PADs
by Cinzia Milito, Valentina Soccodato, Giulia Collalti, Alison Lanciarotta, Ilaria Bertozzi, Marcello Rattazzi, Riccardo Scarpa and Francesco Cinetto
Vaccines 2021, 9(6), 626; https://doi.org/10.3390/vaccines9060626 - 9 Jun 2021
Cited by 12 | Viewed by 2928
Abstract
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; [...] Read more.
Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients. Full article
13 pages, 439 KiB  
Review
SARS-CoV-2 Vaccination and Anaphylaxis: Recommendations of the French Allergy Community and the Montpellier World Health Organization Collaborating Center
by Luciana Kase Tanno, Frédéric Berard, Etienne Beaudoin, Alain Didier and Pascal Demoly
Vaccines 2021, 9(6), 560; https://doi.org/10.3390/vaccines9060560 - 27 May 2021
Cited by 12 | Viewed by 4374
Abstract
Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have been reported after SARS-CoV2 RNA vaccines. Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. This risk is estimated [...] Read more.
Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have been reported after SARS-CoV2 RNA vaccines. Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. This risk is estimated at 1/1,000,000 in the context of vaccine safety surveillance programs. The COVID-19 vaccination is rolling-out vastly in different courtiers and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care. The here presented recommendations and follow-up from the French allergy community and the Montpellier WHO Collaborating Center in order to support the vaccination program and intends to support to healthcare professionals in their daily basis. Full article
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19 pages, 1271 KiB  
Review
Allergic Reactions to Current Available COVID-19 Vaccinations: Pathophysiology, Causality, and Therapeutic Considerations
by Nicholas G. Kounis, Ioanna Koniari, Cesare de Gregorio, Dimitris Velissaris, Konstantinos Petalas, Aikaterini Brinia, Stelios F. Assimakopoulos, Christos Gogos, Sophia N. Kouni, George N. Kounis, GianFranco Calogiuri and Ming-Yow Hung
Vaccines 2021, 9(3), 221; https://doi.org/10.3390/vaccines9030221 - 5 Mar 2021
Cited by 130 | Viewed by 21175
Abstract
Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are [...] Read more.
Vaccines constitute the most effective medications in public health as they control and prevent the spread of infectious diseases and reduce mortality. Similar to other medications, allergic reactions can occur during vaccination. While most reactions are neither frequent nor serious, anaphylactic reactions are potentially life-threatening allergic reactions that are encountered rarely, but can cause serious complications. The allergic responses caused by vaccines can stem from activation of mast cells via Fcε receptor-1 type I reaction, mediated by the interaction between immunoglobulin E (IgE) antibodies against a particular vaccine, and occur within minutes or up to four hours. The type IV allergic reactions initiate 48 h after vaccination and demonstrate their peak between 72 and 96 h. Non-IgE-mediated mast cell degranulation via activation of the complement system and via activation of the Mas-related G protein-coupled receptor X2 can also induce allergic reactions. Reactions are more often caused by inert substances, called excipients, which are added to vaccines to improve stability and absorption, increase solubility, influence palatability, or create a distinctive appearance, and not by the active vaccine itself. Polyethylene glycol, also known as macrogol, in the currently available Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines, and polysorbate 80, also known as Tween 80, in AstraZeneca and Johnson & Johnson COVID-19 vaccines, are excipients mostly incriminated for allergic reactions. This review will summarize the current state of knowledge of immediate and delayed allergic reactions in the currently available vaccines against COVID-19, together with the general and specific therapeutic considerations. These considerations include: The incidence of allergic reactions and deaths under investigation with the available vaccines, application of vaccination in patients with mast cell disease, patients who developed an allergy during the first dose, vasovagal symptoms masquerading as allergic reactions, the COVID-19 vaccination in pregnancy, deaths associated with COVID-19 vaccination, and questions arising in managing of this current ordeal. Careful vaccine-safety surveillance over time, in conjunction with the elucidation of mechanisms of adverse events across different COVID-19 vaccine platforms, will contribute to the development of a safe vaccine strategy. Allergists’ expertise in proper diagnosis and treatment of allergic reactions is vital for the screening of high-risk individuals. Full article
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12 pages, 259 KiB  
Review
Immune Response to Vaccination in Patients with Psoriasis Treated with Systemic Therapies
by Andrea Chiricozzi, Paolo Gisondi, Francesco Bellinato and Giampiero Girolomoni
Vaccines 2020, 8(4), 769; https://doi.org/10.3390/vaccines8040769 - 16 Dec 2020
Cited by 30 | Viewed by 5405
Abstract
Psoriasis is a chronic inflammatory skin disease usually treated with immunomodulatory/immunosuppressive agents. The use of these agents has been associated with an increased susceptibility to infections. Vaccination might represent a critical aspect in the management of patients with psoriasis treated with immunomodulatory/immunosuppressive therapies. [...] Read more.
Psoriasis is a chronic inflammatory skin disease usually treated with immunomodulatory/immunosuppressive agents. The use of these agents has been associated with an increased susceptibility to infections. Vaccination might represent a critical aspect in the management of patients with psoriasis treated with immunomodulatory/immunosuppressive therapies. This narrative review aimed to provide an overview on the immune response to vaccines in subjects treated with systemic agents used to treat patients with moderate to severe psoriasis. Publications appearing in PubMed, Scopus, and ISI–Web of Knowledge database were selected using Medical Subject Headings key terms. Overall, published data confirmed that vaccination with attenuated live vaccines during therapy with immunomodulatory/immunosuppressive therapies should be avoided. For nonlive vaccines, a more favorable safety profile of biologic agents compared to conventional systemic agents is described as the humoral response to vaccines is in general well-preserved. Treatment with cyclosporine and methotrexate is associated with lower antibody titers to vaccines, and thus these agents are better discontinued during vaccination. In contrast, treatment with biological agents is not associated with lower antibody response and can thus be continued safely. Full article
13 pages, 412 KiB  
Review
The Risk of COVID-19 Pandemic in Patients with Moderate to Severe Plaque Psoriasis Receiving Systemic Treatments
by Paolo Gisondi, Francesco Bellinato, Andrea Chiricozzi and Giampiero Girolomoni
Vaccines 2020, 8(4), 728; https://doi.org/10.3390/vaccines8040728 - 2 Dec 2020
Cited by 27 | Viewed by 7723
Abstract
Chronic plaque psoriasis is an inflammatory skin disease affecting 2–3% of the general population. Approximately one-third of patients are candidates for systemic immunosuppressive treatments, such as synthetic or biological disease-modifying antirheumatic drugs, because of disease extensions, localization in sensitive or visible areas and/or [...] Read more.
Chronic plaque psoriasis is an inflammatory skin disease affecting 2–3% of the general population. Approximately one-third of patients are candidates for systemic immunosuppressive treatments, such as synthetic or biological disease-modifying antirheumatic drugs, because of disease extensions, localization in sensitive or visible areas and/or resistance to topical treatments. These therapies have been associated with increased risk of infection, including upper respiratory tract viral infection. Psoriasis is frequently associated with cardio-metabolic comorbidities, such as obesity and diabetes, that are risk factors for poor prognosis in the case of coronavirus disease (COVID-19) pneumonia. A narrative review of the literature based on an electronic search of the PubMed® database was undertaken with the objective of investigating whether there is an increased risk of COVID-19 infection in psoriasis patients on systemic treatment. Original articles, such as case reports, published up to 1 November 2020 were included. There is no evidence that patients with moderate-to-severe psoriasis receiving systemic treatments, including biologics, have higher risk of SARS-CoV-2 infection and/or increased hospitalization and death related to COVID-19 compared to the general population. Several case reports described full recovery from COVID-19 with favorable outcomes in psoriasis patients who were being treated with synthetics or biologicals. Nonetheless, caution should be maintained in this setting, and more data are needed to draw definitive conclusions. Full article
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