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Vaccines and Antibodies for Therapy and Prophylaxis

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 72126

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Prof. Dr. Isabella Quinti

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Dipartimento di Medicina Molecolare, Sapienza, Università di Roma, AOU Policlinico Umberto I, Roma, Italy
Interests: primary immunodeficiencies; vaccines; anti-infectious immunity; mucosal immunity
Special Issues, Collections and Topics in MDPI journals

Dr. Raffaele D’Amelio

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Retired, Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, AOU S. Andrea, Via di Grottarossa 1035-1039, 00189 Roma, Italy
Interests: vaccines in normal adults and in immune-mediated inflammatory diseases; microbiota
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Enrico Maggi

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IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy
Interests: study of humoral and cellular immunity to infectious, allergic, and autoimmune antigens

Special Issue Information

Dear Colleagues,

Vaccines date back to more than 200 years ago, when the English doctor Edward Jenner, at the end of the 18th century, in a period lacking any knowledge about microbiology and immunology, had the intuition of inoculating cowpox instead of smallpox, based on the observation that cow milkers had an attenuated, localized infection, but they were protected from the more fearsome, severe, and frequently lethal smallpox, which haunted Europe in that period with periodical outbreaks. After approximately one century, the French chemist Louis Pasteur deepened the studies on vaccines by producing the vaccines for anthrax, rabies, chicken cholera and swine erysipelas. Last century was the golden age for vaccines, and the current, fearful COVID-19 pandemic has demonstrated that effective, innovative vaccines can be prepared in less than one year. Preventive and therapeutic vaccines have been developed for infectious, neoplastic, and allergic diseases.

In 1901, 120 years ago, the first Nobel Prize for Physiology and Medicine was awarded to the German researcher Emil Adolf von Behring for his studies on serum therapy, in particular anti-diphtheria toxin, using the serum of animals immunized with diphtheria toxin. For the first time, the functional activity of antibodies was demonstrated, the structure of which would only be identified very later by Edelman and Porter, who were awarded the Nobel Prize for Physiology and Medicine in 1972. From the pioneering study of von Behring, antibodies have largely been used in diagnosis and therapy, first by using animal sera, then purified polyclonal human antibodies, and lastly monoclonal antibodies. Passive immunotherapy has been frequently used in clinics, and even in the current COVID-19 pandemic, convalescent plasma, hyper-immune immunoglobulins, and monoclonal antibodies have been set up and effectively used.

The aim of the Special Issue on “Vaccines and Antibodies for Therapy and Prophylaxis” is to attract original articles and reviews on anti-infectious, antitumor, and anti-allergic, hyposensitizing, vaccines, including innovative anti-COVID-19 vaccines, in normal people and in immunocompromised patients, as well as the use of antibodies in therapy and prophylaxis, including human immunoglobulin administered by intravenous or subcutaneous route. Moreover, even preclinical, experimental immunization studies, characteristic of basic immunology, are welcome.

Prof. Dr. Isabella Quinti
Dr. Raffaele D’Amelio
Prof. Dr. Enrico Maggi
Guest Editors

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Keywords

vaccines
immunization
passive immunotherapy
infections
tumors
allergic diseases
autoimmune diseases
preventive/therapeutic vaccines
polyclonal antibodies
monoclonal antibodies

Published Papers (10 papers)

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Research

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13 pages, 870 KiB

Open AccessArticle

Short-Term Safety and Psychosocial Impact of the BNT162b2 mRNA COVID-19 Vaccine in Cancer Patients—An Italian Single-Center Experience

by Irene Persano, Massimiliano Cani, Benedetta Del Rio, Giorgia Ferrari, Edoardo Garbo, Elena Parlagreco, Chiara Pisano, Valeria Cetoretta, Marco Donatello Delcuratolo, Fabio Turco, Alessandro Audisio, Cristina Cecchi, Gianmarco Leone, Valerio Maria Napoli, Valentina Bertaglia, Valentina Bianco, Enrica Capelletto, Carmen D’Amiano, Massimo Di Maio, Martina Gianetta, Silvia Novello, Francesco Passiglia, Giorgio Vittorio Scagliotti and Paolo Bironzo Show full author list Hide full author list

Biomedicines 2023, 11(1), 165; https://doi.org/10.3390/biomedicines11010165 - 09 Jan 2023

Viewed by 2204

Abstract

Safety data regarding BNT162b2 in cancer patients (CPs) are scarce. Herein we report the side effects (SEs), the adverse events (AEs), and the patient-reported outcomes (PROs) following BNT162b2 administration in CPs treated at the San Luigi Gonzaga University Hospital. All CPs who agreed to participate in our vaccination campaign received BNT162b2 and were included in the descriptive analysis. An anonymous questionnaire investigating the occurrence of SEs/AEs and PROs was administered to the study population 21 days after the first dose. Pearson’s chi-squared test was used to estimate the risk of experiencing SEs/AEs according to selected variables. A total of 997 patients were included in the study: 62.0% had stage IV cancer, and 68.8% were receiving an active treatment, of whom 15.9% were receiving immunotherapy. SEs/AEs were recorded in 37.1% of cases after the first dose and in 48.5% of cases after the second dose. The most common SEs were muscle pain/local rash (27.9% and 28%, after the first and second dose, respectively). Patients older than 70 years showed lower risk of SEs/AEs, while women showed a higher risk. Before receiving the vaccine, 18.2% of patients felt fearful and/or insecure about the vaccination. After the first dose, 57.5% of patients changed their feelings positively. Our data support the short-term safety of BNT162b2 in CPs, regardless of disease stage and concurrent treatments. Overall, the vaccination showed a positive impact on quality of life. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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13 pages, 1488 KiB

Open AccessArticle

Fourth Dose of mRNA COVID-19 Vaccine Transiently Reactivates Spike-Specific Immunological Memory in People Living with HIV (PLWH)

by Giulia Lamacchia, Lorenzo Salvati, Seble Tekle Kiros, Alessio Mazzoni, Anna Vanni, Manuela Capone, Alberto Carnasciali, Parham Farahvachi, Filippo Lagi, Nicoletta Di Lauria, Arianna Rocca, Maria Grazia Colao, Francesco Liotta, Lorenzo Cosmi, Gian Maria Rossolini, Alessandro Bartoloni, Laura Maggi and Francesco Annunziato

Biomedicines 2022, 10(12), 3261; https://doi.org/10.3390/biomedicines10123261 - 15 Dec 2022

Cited by 5 | Viewed by 1971

Abstract

Background: People Living With HIV (PLWH), with advanced disease, lower CD4+ T cell counts or an unsuppressed HIV viral load can have a suboptimal vaccine response. For this reason, in the current COVID-19 pandemic, they represent a prioritized population for the SARS-CoV-2 fourth (or second booster) vaccine dose. This work aims to investigate the effects of a second booster on the reactivation of the spike-specific humoral and cell-mediated immune responses in PLWH. Methods: A total of eight PLWH, who received a fourth dose of the original mRNA vaccines were enrolled. They were evaluated before and then 7 days, 1 month and 2 months after the injection. The humoral response was assessed via a chemiluminescent immunoassay. Immunophenotyping and the functional evaluation of the SARS-CoV-2-specific cellular immune responses were performed via flow cytometry. Results: Anti-spike IgG levels were above the cut-off value for all subjects at all timepoints. The spike-specific CD4+ T cell response was reactivated one week after the fourth vaccine dose, and on average declined at two months post-vaccination. A similar trend was observed for the spike-specific B cells. A low percentage of spike-specific CD4+ T cells was activated by the B.1.1.529 BA.1 Omicron-spike mutated peptides, and the majority of these cells were reactive to the conserved portions of the spike protein. Similarly, the majority of the spike-specific memory B cells were able to bind both Wuhan and Omicron-spike entire protein. Conclusions: Spike-specific adaptive immune responses are transiently reactivated in PLWH following the fourth mRNA vaccine dose. The breadth of the immune responses to the mutated spike protein provides insight on the possible cross-reactivity for the SARS-CoV-2 variants of concern (VOCs). Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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10 pages, 1623 KiB

Open AccessArticle

Baseline Eosinophil Count as a Potential Clinical Biomarker for Clinical Complexity in EGPA: A Real-Life Experience

by Andrea Matucci, Emanuele Vivarelli, Margherita Perlato, Valentina Mecheri, Matteo Accinno, Lorenzo Cosmi, Paola Parronchi, Oliviero Rossi and Alessandra Vultaggio

Biomedicines 2022, 10(11), 2688; https://doi.org/10.3390/biomedicines10112688 - 24 Oct 2022

Cited by 2 | Viewed by 1647

Abstract

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel necrotizing vasculitis with multiple organ involvement. Despite improvements in clinical management, biomarkers for organ involvement and disease prognosis are still an unmet need. Methods: EGPA patients referred to our immunology clinic were retrospectively reviewed. Demographic/clinical features, eosinophils, ANCA status, eosinophil cationic protein (ECP) and total serum IgE were evaluated at the baseline. Eosinophils, total serum IgE, ECP and ANCA were studied as possible biomarkers for lung and extrapulmonary disease. Results: In total, 167 EGPA patients were recruited for our study. A positive association between eosinophils and peripheral nervous system (PNS) involvement was demonstrated (p <0.001; chi-squared test). Receiver operating characteristic (ROC) curves using the eosinophil count or percentage as predictors of PNS involvement yielded AUC values of 0.75 and 0.67, respectively. ANCA positivity was associated with PNS involvement, while no correlations with clinical parameters were found for ECP and total serum IgE. Patients without extrapulmonary involvement had lower eosinophils (eosinophils: 2844.7 ± 1698 vs. 6373 ± 5468, p < 0.001; eosinophil percentage: 24.6 ± 10% vs. 36.2 ± 15.8, p < 0.001) and were less likely to be ANCA+ (p < 0.001, chi-squared test). Conclusion: Eosinophils in EGPA are an important biomarker and are associated with extrapulmonary involvement. These findings could strengthen the role of anti-eosinophilic drugs in improving extrapulmonary disease. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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11 pages, 2493 KiB

Open AccessArticle

Vaccine mRNA Can Be Detected in Blood at 15 Days Post-Vaccination

by Tudor Emanuel Fertig, Leona Chitoiu, Daciana Silvia Marta, Victor-Stefan Ionescu, Valeriu Bogdan Cismasiu, Eugen Radu, Giulia Angheluta, Maria Dobre, Ana Serbanescu, Mihail Eugen Hinescu and Mihaela Gherghiceanu

Biomedicines 2022, 10(7), 1538; https://doi.org/10.3390/biomedicines10071538 - 28 Jun 2022

Cited by 27 | Viewed by 43163

Abstract

COVID-19 mRNA vaccines effectively reduce incidence of severe disease, hospitalisation and death. The biodistribution and pharmacokinetics of the mRNA-containing lipid nanoparticles (LNPs) in these vaccines are unknown in humans. In this study, we used qPCR to track circulating mRNA in blood at different time-points after BNT162b2 vaccination in a small cohort of healthy individuals. We found that vaccine-associated synthetic mRNA persists in systemic circulation for at least 2 weeks. Furthermore, we used transmission electron microscopy (TEM) to investigate SARS-CoV-2 spike protein expression in human leukemic cells and in primary mononuclear blood cells treated in vitro with the BNT162b2 vaccine. TEM revealed morphological changes suggestive of LNP uptake, but only a small fraction of K562 leukemic cells presented spike-like structures at the cell surface, suggesting reduced levels of expression for these specific phenotypes. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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Review

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17 pages, 609 KiB

Open AccessReview

The Latest Approach of Immunotherapy with Endosomal TLR Agonists Improving NK Cell Function: An Overview

by Irene Veneziani, Claudia Alicata, Lorenzo Moretta and Enrico Maggi

Biomedicines 2023, 11(1), 64; https://doi.org/10.3390/biomedicines11010064 - 27 Dec 2022

Cited by 2 | Viewed by 2362

Abstract

Toll-like receptors (TLRs) are the most well-defined pattern recognition receptors (PRR) of several cell types recognizing pathogens and triggering innate immunity. TLRs are also expressed on tumor cells and tumor microenvironment (TME) cells, including natural killer (NK) cells. Cell surface TLRs primarily recognize extracellular ligands from bacteria and fungi, while endosomal TLRs recognize microbial DNA or RNA. TLR engagement activates intracellular pathways leading to the activation of transcription factors regulating gene expression of several inflammatory molecules. Endosomal TLR agonists may be considered as new immunotherapeutic adjuvants for dendritic cell (DC) vaccines able to improve anti-tumor immunity and cancer patient outcomes. The literature suggests that endosomal TLR agonists modify TME on murine models and human cancer (clinical trials), providing evidence that locally infused endosomal TLR agonists may delay tumor growth and induce tumor regression. Recently, our group demonstrated that CD56^bright NK cell subset is selectively responsive to TLR8 engagement. Thus, TLR8 agonists (loaded or not to nanoparticles or other carriers) can be considered a novel strategy able to promote anti-tumor immunity. TLR8 agonists can be used to activate and expand in vitro circulating or intra-tumoral NK cells to be adoptively transferred into patients. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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14 pages, 922 KiB

Open AccessReview

Therapeutical Targets in Allergic Inflammation

by Lorenzo Salvati, Francesco Liotta, Francesco Annunziato and Lorenzo Cosmi

Biomedicines 2022, 10(11), 2874; https://doi.org/10.3390/biomedicines10112874 - 09 Nov 2022

Cited by 10 | Viewed by 2363

Abstract

From the discovery of IgE to the in-depth characterization of Th2 cells and ILC2, allergic inflammation has been extensively addressed to find potential therapeutical targets. To date, omalizumab, an anti-IgE monoclonal antibody, and dupilumab, an anti-IL-4 receptor α monoclonal antibody, represent two pillars of biologic therapy of allergic inflammation. Their increasing indications and long-term follow-up studies are shaping the many different faces of allergy. At the same time, their limitations are showing the intricate pathogenesis of allergic diseases. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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19 pages, 607 KiB

Open AccessReview

How the Immune System Responds to Allergy Immunotherapy

by Irene Veneziani, Nadine Landolina, Biancamaria Ricci, Oliviero Rossi, Lorenzo Moretta and Enrico Maggi

Biomedicines 2022, 10(11), 2825; https://doi.org/10.3390/biomedicines10112825 - 05 Nov 2022

Cited by 5 | Viewed by 2450

Abstract

IgE-mediated diseases represent a highly diversified and multifactorial group of disorders that can deeply impact the patients’ quality of life. Currently, allergy immunotherapy (AIT) still remains the gold standard for the management of such pathologies. In this review, we comprehensively examine and discuss how AIT can affect both the innate and the adaptive immune responses at different cell levels and propose timing-scheduled alterations induced by AIT by hypothesizing five sequential phases: after the desensitization of effector non-lymphoid cells and a transient increase of IgE (phase 1), high doses of allergen given by AIT stimulate the shift from type 2/type 3 towards type 1 response (phase 2), which is progressively potentiated by the increase of IFN-γ that promotes the chronic activation of APCs, progressively leading to the hyperexpression of Notch1L (Delta4) and the secretion of IL-12 and IL-27, which are essential to activate IL-10 gene in Th1 and ILC1 cells. As consequence, an expansion of circulating memory Th1/Tr1 cells and ILC-reg characterizes the third phase addressed to antagonize/balance the excess of type 1 response (phase 3). The progressive increase of IL-10 triggers a number of regulatory circuits sustained by innate and adaptive immune cells and favoring T-cell tolerance (phase 4), which may also be maintained for a long period after AIT interruption (phase 5). Different administration approaches of AIT have shown a similar tailoring of the immune responses and can be monitored by timely, optimized biomarkers. The clinical failure of this treatment can occur, and many genetic/epigenetic polymorphisms/mutations involving several immunological mechanisms, such as the plasticity of immune responses and the induction/maintenance of regulatory circuits, have been described. The knowledge of how AIT can shape the immune system and its responses is a key tool to develop novel AIT strategies including the engineering of allergen or their epitopes. We now have the potential to understand the precise causes of AIT failure and to establish the best biomarkers of AIT efficacy in each phase of the treatment. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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12 pages, 571 KiB

Open AccessReview

Monoclonal Antibodies for Bacterial Pathogens: Mechanisms of Action and Engineering Approaches for Enhanced Effector Functions

by Fabiola Vacca, Claudia Sala and Rino Rappuoli

Biomedicines 2022, 10(9), 2126; https://doi.org/10.3390/biomedicines10092126 - 30 Aug 2022

Cited by 11 | Viewed by 2998

Abstract

Monoclonal antibody (mAb) therapy has opened a new era in the pharmaceutical field, finding application in various areas of research, from cancer to infectious diseases. The IgG isoform is the most used therapeutic, given its long half-life, high serum abundance, and most importantly, the presence of the Fc domain, which can be easily engineered. In the infectious diseases field, there has been a rising interest in mAbs research to counteract the emerging crisis of antibiotic resistance in bacteria. Various pathogens are acquiring resistance mechanisms, inhibiting any chance of success of antibiotics, and thus may become critically untreatable in the near future. Therefore, mAbs represent a new treatment option which may complement or even replace antibiotics. However, very few antibacterial mAbs have succeeded clinical trials, and until now, only three mAbs have been approved by the FDA. These failures highlight the need of improving the efficacy of mAb therapeutic activity, which can also be achieved with Fc engineering. In the first part of this review, we will describe the mechanisms of action of mAbs against bacteria, while in the second part, we will discuss the recent advances in antibody engineering to increase efficacy of pre-existing anti-bacterial mAbs. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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96 pages, 1956 KiB

Open AccessReview

A Historical Review of Military Medical Strategies for Fighting Infectious Diseases: From Battlefields to Global Health

by Roberto Biselli, Roberto Nisini, Florigio Lista, Alberto Autore, Marco Lastilla, Giuseppe De Lorenzo, Mario Stefano Peragallo, Tommaso Stroffolini and Raffaele D’Amelio

Biomedicines 2022, 10(8), 2050; https://doi.org/10.3390/biomedicines10082050 - 22 Aug 2022

Cited by 9 | Viewed by 8133

Abstract

The environmental conditions generated by war and characterized by poverty, undernutrition, stress, difficult access to safe water and food as well as lack of environmental and personal hygiene favor the spread of many infectious diseases. Epidemic typhus, plague, malaria, cholera, typhoid fever, hepatitis, tetanus, and smallpox have nearly constantly accompanied wars, frequently deeply conditioning the outcome of battles/wars more than weapons and military strategy. At the end of the nineteenth century, with the birth of bacteriology, military medical researchers in Germany, the United Kingdom, and France were active in discovering the etiological agents of some diseases and in developing preventive vaccines. Emil von Behring, Ronald Ross and Charles Laveran, who were or served as military physicians, won the first, the second, and the seventh Nobel Prize for Physiology or Medicine for discovering passive anti-diphtheria/tetanus immunotherapy and for identifying mosquito Anopheline as a malaria vector and plasmodium as its etiological agent, respectively. Meanwhile, Major Walter Reed in the United States of America discovered the mosquito vector of yellow fever, thus paving the way for its prevention by vector control. In this work, the military relevance of some vaccine-preventable and non-vaccine-preventable infectious diseases, as well as of biological weapons, and the military contributions to their control will be described. Currently, the civil–military medical collaboration is getting closer and becoming interdependent, from research and development for the prevention of infectious diseases to disasters and emergencies management, as recently demonstrated in Ebola and Zika outbreaks and the COVID-19 pandemic, even with the high biocontainment aeromedical evacuation, in a sort of global health diplomacy. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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25 pages, 1517 KiB

Open AccessReview

Recent Progress in the Discovery and Development of Monoclonal Antibodies against Viral Infections

by Pardis Mokhtary, Zeinab Pourhashem, Akram Abouei Mehrizi, Claudia Sala and Rino Rappuoli

Biomedicines 2022, 10(8), 1861; https://doi.org/10.3390/biomedicines10081861 - 02 Aug 2022

Cited by 9 | Viewed by 3827

Abstract

Monoclonal antibodies (mAbs), the new revolutionary class of medications, are fast becoming tools against various diseases thanks to a unique structure and function that allow them to bind highly specific targets or receptors. These specialized proteins can be produced in large quantities via the hybridoma technique introduced in 1975 or by means of modern technologies. Additional methods have been developed to generate mAbs with new biological properties such as humanized, chimeric, or murine. The inclusion of mAbs in therapeutic regimens is a major medical advance and will hopefully lead to significant improvements in infectious disease management. Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating. New technologies have been developed to modify the structure of mAbs, thereby increasing efficacy and improving delivery routes. Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks. Full article

(This article belongs to the Special Issue Vaccines and Antibodies for Therapy and Prophylaxis)

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