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Alzheimer's disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer's disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aβ degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer's disease are emphasized. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer's disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer's disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer's disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer's disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer's disease worldwide. [ABSTRACT FROM AUTHOR]

Background and Objectives: The efficacy of COVID‐19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas‐19 clinical trial showed that CP reduces the risk of progression to severe COVID‐19 at 28 days. Here, we aim to study ConPlas‐19 donors and characteristics that associate with high anti‐SARS‐CoV‐2 antibody levels. Materials and Methods: Four‐hundred donors were enrolled in ConPlas‐19. The presence and titres of anti‐SARS‐CoV‐2 antibodies were evaluated by EUROIMMUN anti‐SARS‐CoV‐2 S1 IgG ELISA. Results: A majority of 80.3% of ConPlas‐19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti‐SARS‐CoV‐2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24–3.42), with more than 7 days of COVID‐19 symptoms (RR 1.89; 95% CI 1.05–3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16–5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91–3.06). Conclusion: SARS‐CoV‐2 CP candidate donors' age, duration of COVID‐19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID‐19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks. [ABSTRACT FROM AUTHOR]

Abstract Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy.

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in latestage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is capable of large‐scale transmission and has caused the coronavirus disease 2019 (COVID‐19) pandemic. Patients with COVID‐19 may experience persistent long‐term health issues, known as long COVID. Both acute SARS‐CoV‐2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood‐derived products are important strategies to combat the serious damage caused by COVID‐19. Since the emergence of COVID‐19, various blood‐derived products that target or do not target SARS‐CoV‐2 have been investigated for therapeutic applications. SARS‐CoV‐2‐targeting blood‐derived products, including COVID‐19 convalescent plasma, COVID‐19 hyperimmune globulin, and recombinant anti‐SARS‐CoV‐2 neutralizing immunoglobulin G, are virus‐targeting and can provide immediate control of viral infection in the short term. Non‐SARS‐CoV‐2‐targeting blood‐derived products, including intravenous immunoglobulin and human serum albumin exhibit anti‐inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS‐CoV‐2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood‐derived product therapies for COVID‐19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment. [ABSTRACT FROM AUTHOR]

Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy. [ABSTRACT FROM AUTHOR]

The use of passive immunotherapy, either as plasma or purified antibodies, has been recommended to treat the emerging infectious diseases (EIDs) in the absence of alternative therapeutic options. Here, we compare the neutralization potency of various passive immunotherapy approaches designed to provide the immediate neutralizing antibodies as potential EID treatments. To prepare human plasma and purified IgG, we screened and classified individuals into healthy, convalescent, and vaccinated groups against SARS-CoV-2 using qRT-PCR, anti-nucleocapsid, and anti-spike tests. Moreover, we prepared purified IgG from non-immunized and hyperimmunized rabbits against SARS-CoV-2 spike protein. Human and rabbit samples were used to evaluate the neutralization potency by sVNT. All vaccinated and convalescent human plasma and purified IgG groups, as well as purified IgG from hyperimmunized rabbits, had significantly greater levels of spike-specific antibodies than the control groups. Furthermore, when compared to the other groups, the purified IgG from hyperimmunized rabbits exhibited superior levels of neutralizing antibodies, with an IC50 value of 2.08 μg/ml. Additionally, our results indicated a statistically significant positive correlation between the neutralization IC50 value and the positive endpoint concentration of spike-specific antibodies. In conclusion, our study revealed that purified IgG from hyperimmunized animals has greater neutralization potency than other passive immunotherapy methods and may be the most suitable treatment of critically ill patients in EIDs.

Xin Yao,1 Qingyu Wang,1 Changge Han,1 Jiaojiao Nie,1 Yaotian Chang,1 Lipeng Xu,1 Bingya Wu,1 Jingtian Yan,1 Zhiyuan Chen,1 Wei Kong,1,2 Yuhua Shi,1 Yaming Shan1,2 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of ChinaCorrespondence: Yaming Shan, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, People’s Republic of China, Tel +86 133 2446 4361, Email shanym@jlu.edu.cnIntroduction: Broadly neutralizing antibodies (bNAbs) have the ability to neutralize a considerable breadth of genetically diverse human immunodeficiency virus (HIV) strains. Passive immunization can potentially provide protection against HIV infection in animal models. However, the direct antibody infusion effect is limited due to the short half-life and deficient immunogenicity of the antibody. As an alternative strategy, we propose the use of nano viral vectors, specifically the adeno-associated virus (AAV), to continuously and systematically produce bNAbs against HIV.Methods: Plasmids expressing bNAbs PG9, PG16, 10E8, and NIH45-46 antibodies were constructed, targeting three different epitopes of HIV. Additionally, the bNAbs gene mediated by rAAV8 was administered to generate long-term expression with a single injection. We established both single and combined immunization groups. The neutralizing activity of antibodies expressed in mice sera was subsequently evaluated.Results: The expression of bNAbs in BALB/c mice can last for > 24 weeks after a single intramuscular injection of rAAV8. Further studies show that neutralization of the HIV pseudovirus by sera from co-immunized mice with rAAV8 expressing 10E8 and PG16 was enhanced compared with mice immunized with 10E8 or PG16 alone.Conclusion: The prolonged expression of neutralizing antibodies can be maintained over long periods in BALB/c mice. This combined immunization is a promising candidate strategy for HIV treatment.Graphical Abstract: Keywords: AAV delivery, HIV therapy, passive immunotherapy, combined immunotherapy

Alzheimer’s disease, the most common type of dementia worldwide, lacks effective disease-modifying therapies despite significant research efforts. Passive anti-amyloid immunotherapies represent a promising avenue for Alzheimer’s disease treatment by targeting the amyloid-beta peptide, a key pathological hallmark of the disease. This approach utilizes monoclonal antibodies designed to specifically bind amyloid beta, facilitating its clearance from the brain. This review offers an original and critical analysis of anti-amyloid immunotherapies by exploring several aspects. Firstly, the mechanisms of action of these therapies are reviewed, focusing on their ability to promote Aβ degradation and enhance its efflux from the central nervous system. Subsequently, the extensive history of clinical trials involving anti-amyloid antibodies is presented, from initial efforts using first-generation molecules leading to mixed results to recent clinically approved drugs. Along with undeniable progress, the authors also highlight the pitfalls of this approach to offer a balanced perspective on this topic. Finally, based on its potential and limitations, the future directions of this promising therapeutic strategy for Alzheimer’s disease are emphasized.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is capable of large‐scale transmission and has caused the coronavirus disease 2019 (COVID‐19) pandemic. Patients with COVID‐19 may experience persistent long‐term health issues, known as long COVID. Both acute SARS‐CoV‐2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood‐derived products are important strategies to combat the serious damage caused by COVID‐19. Since the emergence of COVID‐19, various blood‐derived products that target or do not target SARS‐CoV‐2 have been investigated for therapeutic applications. SARS‐CoV‐2‐targeting blood‐derived products, including COVID‐19 convalescent plasma, COVID‐19 hyperimmune globulin, and recombinant anti‐SARS‐CoV‐2 neutralizing immunoglobulin G, are virus‐targeting and can provide immediate control of viral infection in the short term. Non‐SARS‐CoV‐2‐targeting blood‐derived products, including intravenous immunoglobulin and human serum albumin exhibit anti‐inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS‐CoV‐2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood‐derived product therapies for COVID‐19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology.

Allergy, the immunological hypersensitivity to innocuous environmental compounds, is a global health problem. The disease triggers, allergens, are mostly proteins contained in various natural sources such as plant pollen, animal dander, dust mites, foods, fungi, and insect venoms. Allergies can manifest with a wide range of symptoms in various organs and be anything from just tedious to life-threatening. A majority of all allergy patients are self-treated with symptom-relieving medicines, while allergen immunotherapy (AIT) is the only causative treatment option. This review will aim to give an overview of the state-of-the-art allergy management, including the use of new biologics and the application of biomarkers, and a special emphasis and discussion on current research trends in the field of AIT. Conventional AIT has proven effective, but the years-long treatment compromises patient compliance. Moreover, AIT is typically not offered for food allergies. Hence, there is a need for new, effective, and safe AIT methods. Novel routes of administration (e.g. oral and intralymphatic), hypoallergenic AIT products, and more effective adjuvants hold great promise. Most recently, the development of allergen-specific monoclonal antibodies for passive immunotherapy may also allow the treatment of patients currently not treated or treatable. [ABSTRACT FROM AUTHOR]

Envenomations induced by animal bites and stings constitute a significant public health burden. Even though a standardized protocol does not exist, parenterally administered polyclonal antivenoms remain the mainstay in snakebite therapy. There is a prevailing opinion that their application by the i.m. route has poor efficacy and that i.v. administration should preferentially be chosen in order to achieve better accomplishment of the antivenom therapeutic activity. Recently, it has been demonstrated that neutralization not only in the systemic circulation but also in the lymphatic system might be of great importance for the clinical outcome since it represents another relevant body compartment through which the absorption of the venom components occurs. In this review, the present-day and summarized knowledge of the laboratory and clinical findings on the i.v. and i.m. routes of antivenom administration is provided, with a special emphasis on the contribution of the lymphatic system to the process of venom elimination. Until now, antivenom-mediated neutralization has not yet been discussed in the context of the synergistic action of both blood and lymph. A current viewpoint might help to improve the comprehension of the venom/antivenom pharmacokinetics and the optimal approach for drug application. There is a great need for additional dependable, practical, well-designed studies, as well as more practice-related experience reports. As a result, opportunities for resolving long-standing disputes over choosing one therapeutic principle over another might be created, improving the safety and effectiveness of snakebite management. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is a concern about a possible deleterious effect of pathogen reduction (PR) with methylene blue (MB) on the function of immunoglobulins of COVID‐19 convalescent plasma (CCP). We have evaluated whether MB‐treated CCP is associated with a poorer clinical response compared to other inactivation systems at the ConPlas‐19 clinical trial. Materials and Methods: This was an ad hoc sub‐study of the ConPlas‐19 clinical trial comparing the proportion of patients transfused with MB‐treated CCP who had a worsening of respiration versus those treated with amotosalen (AM) or riboflavin (RB). Results: One‐hundred and seventy‐five inpatients with SARS‐CoV‐2 pneumonia were transfused with a single CCP unit. The inactivation system of the CCP units transfused was MB in 90 patients (51.4%), RB in 60 (34.3%) and AM in 25 (14.3%). Five out of 90 patients (5.6%) transfused with MB‐treated CCP had worsening respiration compared to 9 out of 85 patients (10.6%) treated with alternative PR methods (p = 0.220). Of note, MB showed a trend towards a lower rate of respiratory progressions at 28 days (risk ratio, 0.52; 95% confidence interval, 0.18–1.50). Conclusion: Our data suggest that MB‐treated CCP does not provide a worse clinical outcome compared to the other PR methods for the treatment of COVID‐19. [ABSTRACT FROM AUTHOR]

Immunotherapy is a developing treatment for advanced breast cancer. Immunotherapy has clinical significance for the treatment of triple-negative breast cancers and human epidermal growth factor receptor-2 positive (HER2+) breast cancers. As a proved effective passive immunotherapy, clinical application of the monoclonal antibodies trastuzumab, pertuzumab and T-DM1 (adotrastuzumab emtansine) has significantly improved the survival of patients with HER2+ breast cancers. Immune checkpoint inhibitors that block programmed death receptor-1 and its ligand (PD-1/PD-L1) have also shown benefits for breast cancer in various clinical trials. Adoptive T-cell immunotherapies and tumor vaccines are emerging as novel approaches to treating breast cancer, but require further study. This article reviews recent advances in immunotherapy for HER2+ breast cancers. [ABSTRACT FROM AUTHOR]

Summary: Lecanemab, an anti-amyloid antibody with effects on biomarker and clinical endpoints in early Alzheimer's Disease (AD), was granted accelerated approval by the FDA in 2023 and regulatory review in Europe is ongoing. We estimate the population potentially eligible for treatment with lecanemab in the 27 EU countries to 5.4 million individuals. Treatment costs would exceed 133 billion EUR per year if the drug is priced similarly as in the United States, amounting to over half of the total pharmaceutical expenditures in the EU. This pricing would be unsustainable; the ability to pay for high-priced therapies varies substantially across countries. Pricing similarly to what has been announced for the United States may place the drug out of reach for patients in some European countries. Disparities in access to novel amyloid-targeting agents may further deepen the inequalities across Europe in health outcomes. As representatives of the European Alzheimer's Disease Consortium Executive Committee, we call for pricing policies that allow eligible patients across Europe to access important innovations, but also continued investments in research and development. Infrastructure to follow up the usage of new therapies in routine care and new payment models may be needed to address affordability and inequalities in patient access.

Alzheimer’s disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer’s disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer’s disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer’s disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer’s disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer’s disease worldwide.

Abstract Background Immunocompromised (IC) patients are at increased risk of severe and/or prolonged COVID-19. Main text The recent study by Scaglione et al., addresses the issue of IC outpatients with SARS-CoV-2 infection. Authors describe the real-life use of SARS-CoV-2 antivirals and/or monoclonal antibodies and the clinical benefit in high-risk COVID-19 patients. The study supports the use of early combination therapy in a subgroup of extremely high risk patients, and considers the combined strategy as a gold standard regimen to both increase the effectiveness of early treatment, especially in IC individuals, and, reduce the emergence of SARS-CoV-2 escape mutants. Conclusion A tailored and standardised therapeutic approach in case of IC out and inpatients with SARS-CoV-2 infection is needed.

The dominant allergen in cat dander, Felis domesticus allergen 1 (Fel d 1), is a persistent trigger for allergic rhinitis and asthma symptoms. We evaluated the efficacy of Fel d 1 monoclonal antibodies (REGN1908/1909) in preventing cat allergen–induced early asthmatic responses (EARs) in cat-allergic patients with mild asthma. Patients were randomized to single-dose REGN1908/1909 600 mg (n = 29) or placebo (n = 27). The FEV 1 was measured for up to 4 hours in a cat allergen environmental exposure unit up to 85 days after dosing. Assessments included between-group differences in change from baseline in FEV 1 area under the curve (AUC; 0-2 hours) and incidence of EAR (FEV 1 reduction ≥20%). Trial registration: NCT03838731. Single-dose REGN1908/1909 significantly prevented reductions in FEV 1 on days 8, 29, 57, and 85. Most REGN1908/1909 patients did not have an EAR by 4 hours (the last time point tested). In contrast, placebo-treated patients experienced a ≥20% mean FEV 1 reduction on days 8, 29, 57, and 85 after dosing, with most experiencing an EAR within 1 hour. REGN1908/1909-treated patients tolerated 3-fold higher allergen quantities (P <.05 at all time points) versus placebo. REGN1908/1909 substantially reduced skin test reactivity to cat allergen versus placebo at all time points tested (nominal P <.001). REGN1908/1909 was generally well tolerated; no serious adverse events or deaths were reported. Single-dose REGN1908/1909 significantly prevented reductions in FEV 1 in cat-allergic patients with mild asthma on cat allergen environmental exposure unit exposure at 8 days and up to 85 days after dose. [ABSTRACT FROM AUTHOR]

Background: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. Methods: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. Results: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. Conclusions: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway. [ABSTRACT FROM AUTHOR]

• Anti–Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) human hyperimmune Immunoglobulin (HIG) is passive polyclonal immunotherapy of potential value to treat COVID-19. • HIG can be fractionated from pooled convalescent plasma (CP) donations or plasma donated by vaccinated donors • HIG has advantages over a regular convalescent plasma product due to its standardized and controlled high neutralizing antibody content and its increased virus safety. • Donor selection, collection, and testing of plasma for HIG production should comply with testing requirements for COVID-19 donations and general requirements of plasma for fractionation. • The fractionation of plasma rich in SARS-CoV-2 antibodies should meet good manufacturing practices to ensure the quality, safety, and consistency of HIG. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the potential therapeutic value of early passive polyclonal immunotherapy using high-titer convalescent plasma (CCP). Human polyclonal hyperimmune immunoglobulin (HIG) has several advantages over CCP. Unlike CCP, HIG can provide standardized and controlled antibody content. It is also subjected to robust pathogen reduction rendering it virally safe and is purified by technologies demonstrated to preserve immunoglobulin neutralization capacity and Fc fragment integrity. This document provides an overview of current practices and guidance for the collection and testing of plasma rich in antibodies against Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) and its industrial fractionation for the manufacture of quality-assured and safe HIG. Considerations are also given to the production of HIG preparations in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Abstract Background Humoral immunity plays an important role in the prevention of canine distemper. Anti-CD virus (CDV) antibody has strong antiviral activity and is widely used in the treatment of CD. However, with the increase of CD cases, the availability of therapeutic CD antibody fell short of the clinical needs. Results The high-titer antiserum with the high-titer neutralizing activity against CDV was obtained from the donkeys (Dezhou Donkey) immunized with the inactivated CDV vaccine. The donkey anti-CDV IgG was purified from the donkey serum, which was identified to significantly inhibit the CDV replication in the cultured Vero cells and effectively reduce the clinical symptoms and increase the survival rates (75%) of CDV-infected dogs (Shih-tzu Dog), similar to that treated with the dog-derived anti-CDV IgG. These results indicate that donkey-derived IgG is a potential substitute for dog-derived IgG to treat the CD in clinic. Conclusions Administration of donkey-derived anti-CDV IgG can ameliorate clinical symptoms and inhibit virus replication, thereby increasing the survival of CDV-infected dogs. This study opens up a new source of therapeutic antibody for CD treatment.

Envenomations induced by animal bites and stings constitute a significant public health burden. Even though a standardized protocol does not exist, parenterally administered polyclonal antivenoms remain the mainstay in snakebite therapy. There is a prevailing opinion that their application by the i.m. route has poor efficacy and that i.v. administration should preferentially be chosen in order to achieve better accomplishment of the antivenom therapeutic activity. Recently, it has been demonstrated that neutralization not only in the systemic circulation but also in the lymphatic system might be of great importance for the clinical outcome since it represents another relevant body compartment through which the absorption of the venom components occurs. In this review, the present-day and summarized knowledge of the laboratory and clinical findings on the i.v. and i.m. routes of antivenom administration is provided, with a special emphasis on the contribution of the lymphatic system to the process of venom elimination. Until now, antivenom-mediated neutralization has not yet been discussed in the context of the synergistic action of both blood and lymph. A current viewpoint might help to improve the comprehension of the venom/antivenom pharmacokinetics and the optimal approach for drug application. There is a great need for additional dependable, practical, well-designed studies, as well as more practice-related experience reports. As a result, opportunities for resolving long-standing disputes over choosing one therapeutic principle over another might be created, improving the safety and effectiveness of snakebite management.

Alzheimer's disease is the most frequent form of dementia in aging population and is presently the world's sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer's disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised patients with B-cell depletion agents are at risk for persistence and/or severe SARS-COV-2 infection. We describe a case series of 21 COVID-19 patients under B cell depletion therapy, mostly treated with a combined therapy based on intravenous remdesevir (RDV) and steroid associated with SARS-CoV-2 monoclonal antibodies against Spike glycoprotein and/or hyper-immune convalescent plasma. Methods: This is a single-center longitudinal study. We retrospectively enrolled a total number of 21 B-cell depleted consecutive hospitalized patients with COVID-19 at the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, from November 2020 to December 2021. Demographic characteristics, medical history, clinical presentation, treatment, adverse drug reactions, and clinical and virological outcome were collected for all patients. In a subgroup, we explore immune T cells activation, T cells specific anti-SARS-COV-2 response, and neutralizing antibodies. Results: Twenty-one inpatients with B-cell depletion and SARS-COV-2 infection were enrolled. A median of 1 B cells/mm3 was detected. Eighteen patients presented hypogammaglobulinemia. All patients presented interstitial pneumonia treated with intravenous RDV and steroids. Sixteen patients were treated with monoclonal antibodies against SARS-CoV-2 Spike protein, four patients were treated with SARS-CoV-2 hyper-immune convalescent plasma infusion, and three patients received both treatments. A variable kinetic of T cell activation returning to normal levels at Day 30 after immunotherapy infusion was observed. All treated patients recovered. Conclusion: In COVID-19 immunosuppressed subjects, it is mandatory to establish a prompt, effective, and combined multi-target therapy including oxygen, antiviral, steroid, and antibody-based therapeutics, tailored to the patient’s clinical needs. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials. [ABSTRACT FROM AUTHOR]

During the pre-vaccine era of the COVID-19 pandemic convalescent plasma has once again emerged as a major potential therapeutic form of passive immunization that in specific cases still represents irreplaceable treatment option. There is a growing concern that variable concentration of neutralizing antibodies, present in convalescent plasma which originates from different donors, apparently affects its effectiveness. The drawback can be overcome through the downstream process of immunoglobulin fraction purification into a standardized product of improved safety and efficacy. All modern procedures are quite lengthy processes. They are also based on fractionation of large plasma quantities whose collection is not attainable during an epidemic. When outbreaks of infectious diseases are occurring more frequently, there is a great need for a more sustainable production approach that would be goal-oriented towards assuring easily and readily available immunoglobulin of therapeutic relevance. We propose a refinement strategy for the IgG preparation achieved through simplification and reduction of the processing steps. It was designed as a small but scalable process to offer an immediately available treatment option that would simultaneously be harmonized with an increased availability of convalescent plasma over the viral outbreak time-course. Concerning the ongoing pandemic status of the COVID-19, the proof of concept was demonstrated on anti-SARS-CoV-2 convalescent plasma but is likely applicable to any other type depending on the current needs. It was guided by the idea of persistent keeping of IgG molecules in the solution, so that protection of their native structure could be assured. Our manufacturing procedure provided a high-quality IgG product of above the average recovery whose composition profile was analyzed by mass spectrometry as quality control check. It was proved free from IgA and IgM as mediators of adverse transfusion reactions, as well as of any other residual impurities, since only IgG fragments were identified. The proportion of S protein-specific IgGs remained unchanged relative to the convalescent plasma. Undisturbed IgG subclass composition was accomplished as well. However, the fractionation principle affected the final product's capacity to neutralize wild-type SARS-CoV-2 infectivity, reducing it by half. Decrease in neutralization potency significantly correlated with the amount of IgM in the starting material. [ABSTRACT FROM AUTHOR]

[Display omitted] Alzheimer's disease (AD) is the most common neurodegeneration having non-effective treatments. Vaccines or monoclonal antibodies are two typical immunotherapies for AD. Due to Aβ neurotoxicity, most of the treatments target its generation and deposition. However, therapies that specifically target tau protein are also being investigated. UB311 vaccine generates N-terminal anti-Aβ antibodies, that neutralize Aβ toxicity and promote plaque clearance. It is designed to elicit specific B-cell and wide T-cell responses. ACC001 or PF05236806 vaccine has the same Aβ fragment and QS21 as an adjuvant. CAD106 stimulates response against Aβ 1-6. However, Nasopharyngitis and injection site erythema are its side effects. AN1792, the first-generation vaccine was formulated in proinflammatory QS21 adjuvant. However, T-cell epitopes are omitted from the developed epitope AD vaccine with Aβ 1-42 B-cell epitopes. The first-generation vaccine immune response was immensely successful in clearing Aβ, but it was also sufficient to provoke meningoencephalitis. Immunotherapies have been at the forefront of these initiatives in recent years. The review covers the recent updates on active and passive immunotherapy for AD. [ABSTRACT FROM AUTHOR]

IntroductionImmunocompromised patients with B-cell depletion agents are at risk for persistence and/or severe SARS-COV-2 infection. We describe a case series of 21 COVID-19 patients under B cell depletion therapy, mostly treated with a combined therapy based on intravenous remdesevir (RDV) and steroid associated with SARS-CoV-2 monoclonal antibodies against Spike glycoprotein and/or hyper-immune convalescent plasma.MethodsThis is a single-center longitudinal study. We retrospectively enrolled a total number of 21 B-cell depleted consecutive hospitalized patients with COVID-19 at the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, from November 2020 to December 2021. Demographic characteristics, medical history, clinical presentation, treatment, adverse drug reactions, and clinical and virological outcome were collected for all patients. In a subgroup, we explore immune T cells activation, T cells specific anti-SARS-COV-2 response, and neutralizing antibodies.ResultsTwenty-one inpatients with B-cell depletion and SARS-COV-2 infection were enrolled. A median of 1 B cells/mm3 was detected. Eighteen patients presented hypogammaglobulinemia. All patients presented interstitial pneumonia treated with intravenous RDV and steroids. Sixteen patients were treated with monoclonal antibodies against SARS-CoV-2 Spike protein, four patients were treated with SARS-CoV-2 hyper-immune convalescent plasma infusion, and three patients received both treatments. A variable kinetic of T cell activation returning to normal levels at Day 30 after immunotherapy infusion was observed. All treated patients recovered.ConclusionIn COVID-19 immunosuppressed subjects, it is mandatory to establish a prompt, effective, and combined multi-target therapy including oxygen, antiviral, steroid, and antibody-based therapeutics, tailored to the patient’s clinical needs.

During the pre-vaccine era of the COVID-19 pandemic convalescent plasma has once again emerged as a major potential therapeutic form of passive immunization that in specific cases still represents irreplaceable treatment option. There is a growing concern that variable concentration of neutralizing antibodies, present in convalescent plasma which originates from different donors, apparently affects its effectiveness. The drawback can be overcome through the downstream process of immunoglobulin fraction purification into a standardized product of improved safety and efficacy. All modern procedures are quite lengthy processes. They are also based on fractionation of large plasma quantities whose collection is not attainable during an epidemic. When outbreaks of infectious diseases are occurring more frequently, there is a great need for a more sustainable production approach that would be goal-oriented towards assuring easily and readily available immunoglobulin of therapeutic relevance. We propose a refinement strategy for the IgG preparation achieved through simplification and reduction of the processing steps. It was designed as a small but scalable process to offer an immediately available treatment option that would simultaneously be harmonized with an increased availability of convalescent plasma over the viral outbreak time-course. Concerning the ongoing pandemic status of the COVID-19, the proof of concept was demonstrated on anti-SARS-CoV-2 convalescent plasma but is likely applicable to any other type depending on the current needs. It was guided by the idea of persistent keeping of IgG molecules in the solution, so that protection of their native structure could be assured. Our manufacturing procedure provided a high-quality IgG product of above the average recovery whose composition profile was analyzed by mass spectrometry as quality control check. It was proved free from IgA and IgM as mediators of adverse transfusion reactions, as well as of any other residual impurities, since only IgG fragments were identified. The proportion of S protein-specific IgGs remained unchanged relative to the convalescent plasma. Undisturbed IgG subclass composition was accomplished as well. However, the fractionation principle affected the final product’s capacity to neutralize wild-type SARS-CoV-2 infectivity, reducing it by half. Decrease in neutralization potency significantly correlated with the amount of IgM in the starting material.

Abstract Coronavirus disease 2019 (COVID‐19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID‐19 hyperimmune globulin (COVID‐HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP‐CorV (Sinopharm COVID‐19 vaccine). COVID‐HIG shows high‐affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) protein, the receptor‐binding domain (RBD), the N‐terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin‐converting enzyme 2 (hACE2). Pseudotyped and authentic virus‐based assays show that COVID‐HIG displays broad‐spectrum neutralization effects on a wide variety of SARS‐CoV‐2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID‐HIG in an Adv5‐hACE2‐transduced IFNAR−/− mouse model of SARS‐CoV‐2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID‐HIG exhibits neutralization potency similar to that of anti‐SARS‐CoV‐2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID‐HIG against SARS‐CoV‐2 infection and provide reference for subsequent clinical trials.

Passive immunization with polyclonal hyper immunoglobulin (HIG) therapy represents a proven strategy by transferring immunoglobulins to patients to confer immediate protection against a range of pathogens including infectious agents and toxins. Distinct from active immunization, the protection is passive and the immunoglobulins will clear from the system; therefore, administration of an effective dose must be maintained for prophylaxis or treatment until a natural adaptive immune response is mounted or the pathogen/agent is cleared. The current review provides an overview of this technology, key considerations to address different pathogens, and suggested improvements. The review will reflect on key learnings from development of HIGs in the response to public health threats due to Zika, influenza, and severe acute respiratory syndrome coronavirus 2.

Passive immunotherapy is a very promising approach for the treatment of Alzheimer's disease (AD). Among the different antibodies under development, those targeting post-translationally modified Aβ peptides might combine efficient reduction in beta-amyloid accompanied by lower sequestration in peripheral compartments and thus anticipated and reduced treatment-related side effects. In that regard, we recently demonstrated that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to the attenuation of AD-like amyloid pathology in 5xFAD mice. In order to assess novel strategies to enhance the efficacy of passive vaccination approaches, we investigated the role of CD33 for Aβ phagocytosis in transgenic mice treated with an isoD7-Aβ antibody. We crossbred 5xFAD transgenic mice with CD33 knock out (CD33KO) mice and compared the amyloid pathology in the different genotypes of the crossbreds. The knockout of CD33 in 5xFAD mice leads to a significant reduction in Aβ plaques and concomitant rescue of behavioral deficits. Passive immunotherapy of 5xFAD/CD33KO showed a significant increase in plaque-surrounding microglia compared to 5xFAD treated with the antibody. Additionally, we observed a stronger lowering of Aβ plaque load after passive immunotherapy in 5xFAD/CD33KO mice. The data suggest an additive effect of passive immunotherapy and CD33KO in terms of lowering Aβ pathology. Hence, a combination of CD33 antagonists and monoclonal antibodies might represent a strategy to enhance efficacy of passive immunotherapy in AD. [ABSTRACT FROM AUTHOR]

Abstract Background Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer’s disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize l-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice. Methods This work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing l-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ monoclonal antibody characterization by surface plasmon resonance, immunohistochemical staining of human and transgenic mouse brain, and the development and application of isoD7-Aβ ELISA as well as different non-modified Aβ ELISA. For antibody treatment studies, 12 mg/kg anti-isoD7-Aβ antibody K11_IgG2a was applied intraperitoneally to 5xFAD mice for 38 weeks. Treatment controls implemented were IgG2a isotype as negative and 3D6_IgG2a, the parent molecule of bapineuzumab, as positive control antibodies. Behavioral studies included elevated plus maze, pole test, and Morris water maze. Results Our advanced antibody K11 showed a KD in the low nM range and > 400fold selectivity for isoD7-Aβ compared to other Aβ variants. By using this antibody, we demonstrated that formation of isoD7-Aβ may occur after formation of aggregates; hence, the presence of the isoD7-modification differentiates aged Aβ from newly formed peptides. Importantly, we also show that the Tottori mutation responsible for early-onset AD in a Japanese pedigree is characterized by massively accelerated formation of isoD7-Aβ in cell culture. The presence of isoD7-Aβ was verified by K11 in post mortem human cortex and 5xFAD mouse brain tissue. Passive immunization of 5xFAD mice resulted in a significant reduction of isoD7-Aβ and total Aβ in brain. Amelioration of cognitive impairment was demonstrated by Morris water maze, elevated plus maze, pole, and contextual fear conditioning tests. Interestingly, despite the lower abundance of the isoD7-Aβ epitope, the application of anti-isoD7-Aβ antibodies showed comparable treatment efficacy in terms of reduction of brain amyloid and spatial learning but did not result in an increase of plasma Aβ concentration as observed with 3D6 treatment. Conclusions The present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy.

Background: Immunocompromised (IC) patients are at increased risk of severe and/or prolonged COVID-19. Main text: The recent study by Scaglione et al., addresses the issue of IC outpatients with SARS-CoV-2 infection. Authors describe the real-life use of SARS-CoV-2 antivirals and/or monoclonal antibodies and the clinical benefit in high-risk COVID-19 patients. The study supports the use of early combination therapy in a subgroup of extremely high risk patients, and considers the combined strategy as a gold standard regimen to both increase the effectiveness of early treatment, especially in IC individuals, and, reduce the emergence of SARS-CoV-2 escape mutants. Conclusion: A tailored and standardised therapeutic approach in case of IC out and inpatients with SARS-CoV-2 infection is needed. [ABSTRACT FROM AUTHOR]

Background: Humoral immunity plays an important role in the prevention of canine distemper. Anti-CD virus (CDV) antibody has strong antiviral activity and is widely used in the treatment of CD. However, with the increase of CD cases, the availability of therapeutic CD antibody fell short of the clinical needs. Results: The high-titer antiserum with the high-titer neutralizing activity against CDV was obtained from the donkeys (Dezhou Donkey) immunized with the inactivated CDV vaccine. The donkey anti-CDV IgG was purified from the donkey serum, which was identified to significantly inhibit the CDV replication in the cultured Vero cells and effectively reduce the clinical symptoms and increase the survival rates (75%) of CDV-infected dogs (Shih-tzu Dog), similar to that treated with the dog-derived anti-CDV IgG. These results indicate that donkey-derived IgG is a potential substitute for dog-derived IgG to treat the CD in clinic. Conclusions: Administration of donkey-derived anti-CDV IgG can ameliorate clinical symptoms and inhibit virus replication, thereby increasing the survival of CDV-infected dogs. This study opens up a new source of therapeutic antibody for CD treatment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by cognitive impairment with few therapeutic options. Despite many failures in developing AD treatment during the past 20 years, significant advances have been achieved in passive immunotherapy of AD very recently. Here, we review characteristics, clinical trial data, and mechanisms of action for monoclonal antibodies (mAbs) targeting key players in AD pathogenesis, including amyloid-β (Aβ), tau and neuroinflammation modulators. We emphasized the efficacy of lecanemab and donanemab on cognition and amyloid clearance in AD patients in phase III clinical trials and discussed factors that may contribute to the efficacy and side effects of anti-Aβ mAbs. In addition, we provided important information on mAbs targeting tau or inflammatory regulators in clinical trials, and indicated that mAbs against the mid-region of tau or pathogenic tau have therapeutic potential for AD. In conclusion, passive immunotherapy targeting key players in AD pathogenesis offers a promising strategy for effective AD treatment. ● Passive immunotherapy is a major strategy under clinical development for AD treatment. ● Monoclonal antibodies against Aβ including lecanemab and donanemab showed significant efficacy in phase III clinical trials. ● ARIA and brain atrophy cannot be ignored in Aβ-targeted immunotherapy. ● Passive immunotherapy targeting tau and neuroinflammation is at an early stage of development. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is the most frequent form of dementia in aging population and is presently the world’s sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer’s disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD.

Corona virus disease or its pandemic (COVID-19), because of novel corona virus-2 (SARS-nCoV-2), has become a big challenge worldwide to discover an effective therapeutic regime for its prevention and treatment. Researchers and scientists are continuously exploring new ideas and strategies to come up with an effective treatment that can confront against the novel corona virus, but no significant results have been documented in any of the reported study up till. Neither an effective vaccine nor any antiviral therapeutic agent has been approved to treat Covid-19. In the present scenario, immunotherapy by transferring of antibody enriched convalescent sera to the infected patient seems to be one of the promising treatment approaches. This paper focuses on exploring the suitability of using CP transfusion therapy on Covid-19 patients, highlighting the risks and challenges associated with its treatment for gaining maximum clinical benefits and better treatment outcome. The findings derived from the serological assays provide a valuable information that would help to support diagnosis, treatment and prevention of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: The role of convalescent plasma therapy for patients with coronavirus disease 2019 (COVID‐19) is unclear. Methods: We retrospectively compared outcomes in a cohort of critical COVID‐19 patients who received standard care (SC Group) and those who, in addition, received convalescent plasma (CP Group). Results: In total, 40 patients were included in each group. The median patient age was 53.5 years (interquartile range [IQR] 42–60.5), and the majority of patients required invasive ventilation (69, 86.2%). Plasma was harvested from donors after a median of 37 days (IQR 31–46) from the first positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) polymerase chain reaction (PCR) result and 26 days (IQR 21–32) after documented viral clearance; it was administered after a median of 10 days (IQR 9–10) from the onset of symptoms and 2.5 days (IQR 2–4) from admission to intensive care unit. The primary endpoint of improvement in respiratory support status within 28 days was achieved in 26 patients (65%) in the SC Group and 31 patients (77.5%) in the CP Group (p =.32). The 28‐day all‐cause mortality (12.5% vs. 2.5%; p =.22) and viral clearance (65% vs. 55%; p =.49) were not significantly different between the two groups. Convalescent plasma was not significantly associated with the primary endpoint (adjusted hazard ratio 0.87; 95% confidence interval 0.51–1.49; p =.62). Adverse events were balanced between the two study groups. Conclusion: In severe COVID‐19, convalescent plasma therapy was not associated with clinical benefits. Randomized trials are required to confirm our findings. Highlights: In patients with severe influenza, convalescent plasma was associated with improved viral clearance and reduced mortality.In this retrospective observational study of patients with severe COVID‐19, convalescent plasma was not associated with improvement in respiratory support status within 28 days, all‐cause mortality, or viral clearance.Randomized trials are urgently required to confirm these findings. [ABSTRACT FROM AUTHOR]

Passive immunotherapy is a very promising approach for the treatment of Alzheimer’s disease (AD). Among the different antibodies under development, those targeting post-translationally modified Aβ peptides might combine efficient reduction in beta-amyloid accompanied by lower sequestration in peripheral compartments and thus anticipated and reduced treatment-related side effects. In that regard, we recently demonstrated that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to the attenuation of AD-like amyloid pathology in 5xFAD mice. In order to assess novel strategies to enhance the efficacy of passive vaccination approaches, we investigated the role of CD33 for Aβ phagocytosis in transgenic mice treated with an isoD7-Aβ antibody. We crossbred 5xFAD transgenic mice with CD33 knock out (CD33KO) mice and compared the amyloid pathology in the different genotypes of the crossbreds. The knockout of CD33 in 5xFAD mice leads to a significant reduction in Aβ plaques and concomitant rescue of behavioral deficits. Passive immunotherapy of 5xFAD/CD33KO showed a significant increase in plaque-surrounding microglia compared to 5xFAD treated with the antibody. Additionally, we observed a stronger lowering of Aβ plaque load after passive immunotherapy in 5xFAD/CD33KO mice. The data suggest an additive effect of passive immunotherapy and CD33KO in terms of lowering Aβ pathology. Hence, a combination of CD33 antagonists and monoclonal antibodies might represent a strategy to enhance efficacy of passive immunotherapy in AD.

Introduction. The rise of multi-drug-resistant bacteria poses a global threat. In 2017, the World Health Organization identified 12 antibiotic-resistant 'priority pathogens', including Enterobacteriaceae, highlighting the menace of Gram-negative bacteria. Diarrhoeagenic Escherichia coli (DEC)-induced diarrhoea is particularly problematic for travellers and infants. In contrast to other antibiotic alternatives, passive immunotherapy is showing promise by providing immediate and precise protection. However, mammalian-sourced antibodies are costly, hindering large-scale production. Egg-laying chicken-derived IgY antibodies present a cost-effective, high-yield solution, revolutionizing antibody-based therapeutics compared to mammalian IgG. Hypothesis/Gap Statement. This study hypothesized that developing anti-DEC-IgY could combat DEC infections effectively. Aim. The primary aim was to develop anti-DEC-IgY and assess its potential in DEC-induced diarrhoeal management. Method. Chickens were immunized with DEC antigens to induce an immune response. IgY antibodies were extracted from immune eggs and purified using ion-exchange column chromatography. Anti-DEC-IgY's ability to inhibit DEC growth was evaluated through growth inhibition assays. Anti-DEC-IgY's capacity to prevent E. coli adhesion was assessed using mice intestinal mucosa. In vivo experiments measured pathogen colonization reduction and infection severity reduction. P values were calculated to confirm statistical significance. Result. The antibacterial efficacy of anti-DEC-IgY by growth inhibition assay demonstrated that 25 mg ml -1 of IgY could inhibit the DEC growth. The anti-adherence-property was tested using mice intestinal mucosa and found that anti-DEC-IgY could prevent the E. coli adhesion. In vivo results suggest that 12 mg ml -1 of IgY will reduce the pathogen colonization in intestine and reduce the severity of the infection. The P values between the experimental groups confirm the statistical significance of the findings. Conclusion. The study findings suggest that IgY-based passive immunotherapy could be a potential strategy for managing the risks associated with antibiotic-resistant bacterial infections. Additionally, this study paves the way for the development of IgY-related research and applications in India.

Background: Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize l-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice. Methods: This work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing l-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ monoclonal antibody characterization by surface plasmon resonance, immunohistochemical staining of human and transgenic mouse brain, and the development and application of isoD7-Aβ ELISA as well as different non-modified Aβ ELISA. For antibody treatment studies, 12 mg/kg anti-isoD7-Aβ antibody K11_IgG2a was applied intraperitoneally to 5xFAD mice for 38 weeks. Treatment controls implemented were IgG2a isotype as negative and 3D6_IgG2a, the parent molecule of bapineuzumab, as positive control antibodies. Behavioral studies included elevated plus maze, pole test, and Morris water maze. Results: Our advanced antibody K11 showed a KD in the low nM range and > 400fold selectivity for isoD7-Aβ compared to other Aβ variants. By using this antibody, we demonstrated that formation of isoD7-Aβ may occur after formation of aggregates; hence, the presence of the isoD7-modification differentiates aged Aβ from newly formed peptides. Importantly, we also show that the Tottori mutation responsible for early-onset AD in a Japanese pedigree is characterized by massively accelerated formation of isoD7-Aβ in cell culture. The presence of isoD7-Aβ was verified by K11 in post mortem human cortex and 5xFAD mouse brain tissue. Passive immunization of 5xFAD mice resulted in a significant reduction of isoD7-Aβ and total Aβ in brain. Amelioration of cognitive impairment was demonstrated by Morris water maze, elevated plus maze, pole, and contextual fear conditioning tests. Interestingly, despite the lower abundance of the isoD7-Aβ epitope, the application of anti-isoD7-Aβ antibodies showed comparable treatment efficacy in terms of reduction of brain amyloid and spatial learning but did not result in an increase of plasma Aβ concentration as observed with 3D6 treatment. Conclusions: The present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is historically difficult to treat, in part because of the inaccessible nature of brain pathology. Amyloid beta and tau proteins drive pathology by forming toxic oligomers that eventually deposit as insoluble amyloid plaques and neurofibrillary tangles. Recent clinical studies suggest that effective drugs must specifically target oligomers, not native monomers or insoluble fibrils. Passive immunotherapy is a promising pharmaceutical strategy used to specifically target these oligomers in situ. Using the specificity of antibodies coupled with the natural power of the body's immune response, this treatment provides an opportunity for safe clearance of pathogenic protein species from the brain. Passive immunotherapies against amyloid beta and tau oligomers have progressed to clinical trials, with many currently in progress. Biochemical studies of antibody-oligomer complexes have helped identify previously unknown toxic epitopes, thus providing knowledge to the AD field as a whole. This mini-review focuses on the efforts to develop passive immunotherapy treatments for AD and discusses the knowledge gained from recent failures and clinical trials in progress. [ABSTRACT FROM AUTHOR]

Anti-HIV broadly neutralizing antibodies (bNAbs) offer a novel approach to treating, preventing, or curing HIV. Pre-clinical models and clinical trials involving the passive transfer of bNAbs have demonstrated that they can control viremia and potentially serve as alternatives or complement antiretroviral therapy (ART). However, antibody decay, persistent latent reservoirs, and resistance impede bNAb treatment. This review discusses recent advancements and obstacles in applying bNAbs and proposes strategies to enhance their therapeutic potential. These strategies include multi-epitope targeting, antibody half-life extension, combining with current and newer antiretrovirals, and sustained antibody secretion. • Anti-HIV broad neutralizing antibodies (bNAbs) reduce HIV viremia, offering a huge breakthrough in HIV treatment. • However, challenges like viral resistance, viral reservoirs, and antibody decay can hinder bNAb-based treatments. • This article delves into the latest progress, challenges, and possible approaches utilizing bNAbs for treating HIV. [ABSTRACT FROM AUTHOR]