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1.
Semin Neurol ; 42(4): 512-522, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2096904

ABSTRACT

Medication overuse headache (MOH), new daily persistent headache (NDPH), and persistent refractory headache attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection represent a significant burden in terms of disability and quality of life, and a challenge in terms of definition, pathophysiology, and treatment. Regarding MOH, prevention without withdrawal is not inferior to prevention with withdrawal. Preventive medications like topiramate, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies improve chronic migraine with MOH regardless of withdrawal. The differential diagnosis of NDPH is broad and should be carefully examined. There are no guidelines for the treatment of NDPH, but options include a short course of steroids, nerve blocks, topiramate, nortriptyline, gabapentin, CGRP monoclonal antibodies, and onabotulinumtoxinA. The persistence of headache 3 months after SARS-CoV2 infection is a predictor of poor prognosis.


Subject(s)
Botulinum Toxins, Type A , COVID-19 , Headache Disorders, Secondary , Headache Disorders , Humans , Calcitonin Gene-Related Peptide/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Quality of Life , Topiramate/therapeutic use , RNA, Viral/therapeutic use , COVID-19/complications , COVID-19/drug therapy , SARS-CoV-2 , Headache Disorders, Secondary/diagnosis , Headache Disorders, Secondary/drug therapy , Headache/diagnosis , Headache/drug therapy , Antibodies, Monoclonal/therapeutic use
2.
Rev Esp Quimioter ; 35 Suppl 3: 16-19, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2091723

ABSTRACT

The COVID-19 pandemic has boosted significant research in developing monoclonal antibodies (mAbs) to treat and prevent SARS-CoV-2 infection. Clinical trials have shown that mAbs are safe and effective in preventing hospitalization and death in patients with mild to moderate COVID-19 risk factors for progression. mAbs have also been effective for treating severe disease in seronegative patients and preventing COVID-19. So far, studies have been carried out in a largely unvaccinated population at a time when the omicron variant was not described. Future research should address these limitations and provide information on specific population groups, including immunosuppressed and previously infected individuals.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , Antibodies, Neutralizing/therapeutic use , Neutralization Tests , SARS-CoV-2 , Antibodies, Viral/therapeutic use , Pandemics , Spike Glycoprotein, Coronavirus , Viral Envelope Proteins , Membrane Glycoproteins , Antibodies, Monoclonal/therapeutic use
3.
J Basic Clin Physiol Pharmacol ; 33(6): 727-733, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2089488

ABSTRACT

Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The idiotype based hypothesis is discussed in this paper in order to produce effective anti-idiotype vaccinations. Polyclonal anti-idiotype reagents have been shown to be more successful in animal models, and a better understanding of the immune response in humans supports the idea that polyclonal anti-idiotype vaccines will be more effective than monoclonal-based anti-idiotype vaccines. This innovative approach can be used to produce therapeutic antibodies in a Biotech-standard manner. The idiotype network has been tweaked in the lab to provide protection against a variety of microbiological diseases. Antibodies to image-idiotype antigens, both internal and non-internal, can elicit unique immune responses to antigens. The current outbreak of severe acute respiratory syndrome 2 (SARS-2) has presented a fantastic chance to use idiotype/anti-idiotype antibodies as a protective regimen, which might be used to treat COVID-19 patients. The development of various effective vaccinations has been crucial in the pandemic's management, but their effectiveness has been limited. In certain healthy people, the development of viral variations and vaccinations can be linked to rare off-target or hazardous effects, such as allergic responses, myocarditis and immune-mediated thrombosis and thrombocytopenia. Many of these occurrences are most likely immune-mediated. The current analysis reveals successful idiotype/anti-idiotype antibody uses in a variety of viral illnesses, emphazising their importance in the COVID-19 pandemic.


Subject(s)
COVID-19 , Vaccines , Humans , Animals , Antibodies, Monoclonal/therapeutic use , Pandemics/prevention & control , Immunoglobulin Idiotypes , Antibodies, Anti-Idiotypic/therapeutic use
4.
BMC Infect Dis ; 22(1): 793, 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2079395

ABSTRACT

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited. METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients. RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events. CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Secondary Prevention , Retrospective Studies , COVID-19/drug therapy , Antiviral Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use
5.
Ann Med ; 54(1): 2856-2860, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2077366

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 continues to have a serious impact on public health worldwide. Most patients develop mild to moderate symptoms and recover without requiring special treatment, but up to 15% develop severe (dyspnea, hypoxia, lung involvement) or critical symptoms (respiratory failure, septic shock, thromboembolism, multiorgan dysfunction). Although vaccination is having a substantial impact on case numbers, hospitalizations and deaths, there remains a need for new effective treatments against COVID-19. METHODS: This short review aims at reporting on current therapeutics against SARS-CoV-2 focussing on new drugs authorized in the European Union, describing the treatment strategies and the clinical recommendations for the management of hospitalized and non-hospitalized COVID-19 patients based on the available guidelines for clinical practice. RESULTS: New effective drugs, like antiviral medications and monoclonal antibodies, have been developed as therapy against severe and life-threatening disease courses. Specifically, the European Medicines Agency has authorized two antiviral medicines (nirmatrelvir/ritonavir, remdesivir), supporting also early use of molnupiravir before marketing authorization, and four monoclonal antibodies (regdanvimab, casirivimab/imdevimab, sotrovimab, tixagevimab/cilgavimab). In addition, three drugs (anakinra, tocilizumab, baricitinib) previously authorized for the treatment of rheumatoid arthritis are also available to treat COVID-19. CONCLUSIONS: Recommendations and guidelines for clinical practice should be regularly updated as further evidence becomes available in favour or against specific interventions, to inform all stakeholders involved in the health care of COVID-19 patients both in the community and in the hospital setting, aiming at improving the quality of care and therefore the patient outcome.KEY MESSAGESCOVID-19 has been recognized as a multisystem disorder affecting many body systems; this wide spectrum of clinical patterns made difficult an appropriate choice of treatments able to counteract severe symptoms of the disease and alleviate the burden on the healthcare system.New effective drugs, like antiviral medications and monoclonal antibodies, have been developed and approved by the European Medicines Agency as therapy against severe and life-threatening disease courses.Recommendations and guidelines should be regularly updated as further evidence becomes available in favour or against specific interventions aiming at improving the quality of care and therefore the patient outcome.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Pandemics , Ritonavir , Interleukin 1 Receptor Antagonist Protein , European Union , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Hospitalization
6.
Sci Rep ; 12(1): 17561, 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2077116

ABSTRACT

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70-80% reduction in relative risk; absolute reduction of 35-40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Humans , SARS-CoV-2 , Network Meta-Analysis , Bayes Theorem , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing
7.
Epidemiol Mikrobiol Imunol ; 71(3): 171-174, 2022.
Article in English | MEDLINE | ID: covidwho-2072922

ABSTRACT

This study describes a cohort of 223 patients who received anti-S protein monoclonal antibody (mAb) treatment for COVID-19 after having met the indication criteria set by the national guidelines in the Czech Republic at the time. The authors compare the vaccinated and unvaccinated subpopulations of this cohort. The results show that most of the patients (73.5%) already had significant circulating levels of anti-S antibodies detectable at the time of treatment. The authors confirm a positive correlation between number of vaccine doses and S-protein antibody levels. The data show, that vaccinated patients are overall less likely to be hospitalized than unvaccinated ones. The authors recommend a change in the national guidelines for mAb treatment in the Czech Republic.


Subject(s)
Antibodies, Monoclonal , COVID-19 , Humans , Antibodies, Monoclonal/therapeutic use , Vaccination , Czech Republic/epidemiology , Cohort Studies , Antibodies, Viral
9.
Cell Rep ; 41(5): 111528, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2060517

ABSTRACT

The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Humans , SARS-CoV-2 , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/genetics , Neutralization Tests , Antibodies, Viral/therapeutic use , Viral Envelope Proteins , Membrane Glycoproteins/genetics , Antibodies, Neutralizing/therapeutic use
10.
JAMA Dermatol ; 158(11): 1327-1330, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2058992

ABSTRACT

This case series describes the outcomes of COVID-19 and SARS-CoV-2 vaccination in patients with atopic dermatitis who have been treated with tralokinumab.


Subject(s)
COVID-19 , Dermatitis, Atopic , Humans , COVID-19/prevention & control , Dermatitis, Atopic/drug therapy , Antibodies, Monoclonal/therapeutic use , Vaccination
11.
West J Emerg Med ; 23(5): 618-622, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-2056166

ABSTRACT

INTRODUCTION: Monoclonal antibody (MAB) infusion is the first treatment to manage coronavirus 2019 (COVID-19) in an outpatient setting. Yet increased risk of severe COVID-19 illness may occur from inequities in social determinants of health including access to quality healthcare. Given the safety-net nature of emergency departments (ED), a model that puts them at the center of MAB infusion may better reach underserved patients than models that require physician referral and distribute MAB at outpatient infusion centers. We examined characteristics of two groups of patients who received MAB infusion in the Robert Wood Johnson University Hospital (RWJUH) ED in New Brunswick, New Jersey: 1) patients who tested positive for COVID-19 in the ED and received ED infusion; and 2) patients who tested positive elsewhere and were referred to the ED for infusion. The process for the latter group was similar to the more common national model of patients testing COVID-19 positive in the community and then being referred to an infusion center for MAB therapy. METHODS: We performed a cross-sectional retrospective health record review of all adult patients presenting to the ED from November 20, 2020-March 15, 2021 who received MAB infusion at RWJUH ED (N = 486). Patients were identified through the electronic health record system by an administrative query, with manual chart review for any additional characteristics not available through the query. We compared the two groups using chi-squared tests for categorical variables and t-tests for continuous variables. RESULTS: We found higher proportions of Black (18% vs 6% P < 0.001, statistically significant), Hispanic (19% vs 11% P = 0.02), Medicaid (12% vs 9% P = 0.01), and uninsured (17% vs 8% P = 0.01) patients who tested positive for COVID-19 in their ED visit and then received MAB therapy during their visit than patients tested elsewhere in the community and referred to the ED for MAB therapy. CONCLUSION: These findings suggest that providing MAB infusion in the ED allows increased access for patients traditionally marginalized from the healthcare system, who may be at risk of longer disease duration and complications from COVID-19.


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Adult , Antibodies, Monoclonal/therapeutic use , COVID-19/drug therapy , Cross-Sectional Studies , Emergency Service, Hospital , Humans , Retrospective Studies
12.
Cell Rep Med ; 3(7): 100678, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-2042205

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) are among the treatments recommended for high-risk ambulatory persons with coronavirus 2019 (COVID-19). Here, we study viral culture dynamics post-treatment in a subset of participants receiving the mAb bamlanivimab in the ACTIV-2 trial (ClinicalTrials.gov: NCT04518410). Viral load by qPCR and viral culture are performed from anterior nasal swabs collected on study days 0 (day of treatment), 1, 2, 3, and 7. Treatment with mAbs results in rapid clearance of culturable virus. One day after treatment, 0 of 28 (0%) participants receiving mAbs and 16 of 39 (41%) receiving placebo still have culturable virus (p < 0.0001). Recrudescence of culturable virus is detected in three participants with emerging mAb resistance and viral RNA rebound. While further studies are necessary to fully define the relationship between shed culturable virus and transmission, these results raise the possibility that mAbs may offer immediate (household) and public-health benefits by reducing onward transmission.


Subject(s)
COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19/drug therapy , Humans , SARS-CoV-2
13.
Clin Immunol ; 244: 109130, 2022 11.
Article in English | MEDLINE | ID: covidwho-2041623

ABSTRACT

Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and anti-receptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naïve B cells, and maintaining a long term vaccine response.


Subject(s)
COVID-19 , Receptors, Interleukin-4 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , COVID-19 Vaccines , Humans , Interleukin-4 , RNA , Receptors, Antigen, B-Cell
14.
Microbiol Spectr ; 10(5): e0215222, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2038253

ABSTRACT

Monoclonal antibodies (MAbs) targeting the Spike glycoprotein of SARS-CoV-2 is a key strategy to prevent severe COVID-19. Here, the efficacy of two monoclonal antibody bitherapies against SARS-CoV-2 was assessed on 92 patients at high risk of severe COVID-19 between March and October 2021 (Bichat-Claude Bernard Hospital, Paris, France). Nine patients died despite appropriate management. From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy (P = 0.045). The emergence of several mutations on the Spike protein known to diminish antiviral efficacy was observed from 1 to 3 weeks after infusion. The Q493R mutation was frequently selected, located in a region of joint structural overlap by Bamlanivimab/Etsevimab antibodies. Despite that this study was done on former SARS-CoV-2 variants (Alpha and Delta), the results provide new insights into resistance mechanisms in SARS-CoV-2 antibodies neutralization escape and should be considered for current and novel variants. IMPORTANCE Monoclonal antibody bitherapies (MAbs) are commonly prescribed to treat severe SARS-CoV-2-positive patients, and the rapid growth of resistance mutation emergence is alarming globally. To explore this issue, we conducted both clinical and genomic analyses of SARS-CoV-2 in a series of patients treated in 2021. We first noticed that the two dual therapies prescribed during the study had different kinetics of viral load decay. Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/therapeutic use , Neutralization Tests , COVID-19/drug therapy , Antibodies, Viral , Antiviral Agents/therapeutic use , Antibodies, Neutralizing
15.
Viruses ; 14(9)2022 09 09.
Article in English | MEDLINE | ID: covidwho-2033136

ABSTRACT

Evusheld® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered for prolonged half-life by modifying the Fc fragment, thus creating a long-acting antibody (LAAB). We review here preclinical development, baseline and treatment-emergent resistance, clinical efficacy from registration trials, and real-world post-marketing evidence. The combination was initially approved for pre-exposure prophylaxis at the time of the SARS-CoV-2 Delta VOC wave based on a trial conducted in unvaccinated subjects when the Alpha VOC was dominant. Another trial also conducted at the time of the Alpha VOC wave proved efficacy as early treatment in unvaccinated patients and led to authorization at the time of the BA.4/5 VOC wave. Tixagevimab was ineffective against any Omicron sublineage, so cilgavimab has so far been the ingredient which has made a difference. Antibody monotherapy has a high risk of selecting for immune escape variants in immunocompromised patients with high viral loads, which nowadays represent the main therapeutic indication for antibody therapies. Among Omicron sublineages, cilgavimab was ineffective against BA.1, recovered efficacy against BA.2 and BA.2.12.1, but lost efficacy again against BA.4/BA.5 and BA.2.75. Our analysis indicated that Evusheld® has been used during the Omicron VOC phase without robust clinical data of efficacy against this variant and suggested that several regulatory decisions regarding its use lacked consistency. There is an urgent need for new randomized controlled trials in vaccinated, immunocompromised subjects, using COVID-19 convalescent plasma as a control arm.


Subject(s)
COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19/therapy , Clinical Trials as Topic , Drug Combinations , Humans , Immunization, Passive , Immunoglobulin Fc Fragments , SARS-CoV-2
16.
Curr Opin Infect Dis ; 35(4): 280-287, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-2032206

ABSTRACT

PURPOSE OF REVIEW: Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to provide an overview of mAbs in clinical use against respiratory viruses, highlight factors that modulate mAb clinical efficacy, and provide a perspective on future innovations in the field. This review focuses on publications from the last year. RECENT FINDINGS: Historically, clinical development of a single mAb has taken over a decade. The COVID-19 pandemic has demonstrated that this timeframe can be reduced to less than a year and has catalyzed rapid innovations in the field. Several novel mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization by the Food and Drug Administration (FDA) for the early treatment of mild to moderate COVID-19. However, the majority of these mAbs have ultimately failed due to the emergence of variants, highlighting an important lesson about predicting and countering resistance. Novel mAbs are also in clinical use or in late-stage development for the prevention of infection by SARS-CoV-2 and respiratory syncytial virus (RSV) in vulnerable populations. Several factors can be modulated to improve the clinical efficacy of mAbs. For example, Fc modifications can extend mAb half-life and increase respiratory tract bioavailability, both of which are attractive properties for achieving protection against respiratory viruses. SUMMARY: The mAb landscape is rapidly evolving with numerous examples of success and failure. The armamentarium of clinically-available mAbs to protect vulnerable populations is expected to undergo continued growth.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Viruses , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral , COVID-19/prevention & control , Humans , Pandemics , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/prevention & control , SARS-CoV-2
17.
Int J Infect Dis ; 124: 55-64, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2031341

ABSTRACT

OBJECTIVES: Neutralizing monoclonal antibodies (moAbs) improves clinical outcomes in patients with COVID-19 when administered during the initial days of infection. The action of moAbs may impair the generation or maintenance of effective immune memory, similar to that demonstrated in other viral diseases. We aimed to evaluate short-term memory T-cell responses in patients effectively treated with bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab (SOT). METHODS: Spike (S)-specific T-cell responses were analyzed in 23 patients with COVID-19 (vaccinated or unvaccinated) before and after a median of 50 (range: 28-93) days from moAb treatment, compared with 11 vaccinated healthy controls. T-cell responses were measured by interferon-γ-enzyme-linked immunospot and flow cytometric activation-induced marker assay. RESULTS: No statistically significant difference in S-specific T-cell responses was observed between patients treated with moAb and vaccinated healthy controls. Bamlanivimab/etesevimab and casirivimab/imdevimab groups showed significant increases in cellular responses in paired baseline/postrecovery series, as well as vaccinated patients receiving SOT. In contrast, unvaccinated patients prescribed SOT presented no statistically significant increases in T-cell-responses, suggesting diverse impacts of different moAbs on the evolution of S-specific T-cell responses in vaccinated and unvaccinated patients. CONCLUSION: The moAbs did not hinder short-term memory S-specific T-cell responses in the overall group of patients; however, differences among moAbs must be further investigated both in vaccinated and unvaccinated individuals.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Humans , SARS-CoV-2 , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral
19.
Cell Host Microbe ; 30(9): 1194-1195, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2027966

ABSTRACT

Utilizing monoclonal antibodies to prevent and treat infectious diseases has been accelerated by the COVID-19 pandemic. In this issue of Cell Host & Microbe, Zheng et al. show how a three-monoclonal-antibody cocktail, that defies conventions of "rational design" for a therapeutic agent, functions cooperatively to disrupt coxsackievirus virions.


Subject(s)
COVID-19 , Enterovirus , Antibodies, Monoclonal/therapeutic use , Humans , Pandemics , Virion
20.
Int J Mol Sci ; 23(17)2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-2023744

ABSTRACT

Understanding the biological mechanisms underlying the pH-dependent nature of FcRn binding, as well as the various factors influencing the affinity to FcRn, was concurrent with the arrival of the first recombinant IgG monoclonal antibodies (mAbs) and IgG Fc-fusion proteins in clinical practice. IgG Fc-FcRn became a central subject of interest for the development of these drugs for the comfort of patients and good clinical responses. In this review, we describe (i) mAb mutations close to and outside the FcRn binding site, increasing the affinity for FcRn at acidic pH and leading to enhanced mAb half-life and biodistribution, and (ii) mAb mutations increasing the affinity for FcRn at acidic and neutral pH, blocking FcRn binding and resulting, in vivo, in endogenous IgG degradation. Mutations modifying FcRn binding are discussed in association with pH-dependent modulation of antigen binding and (iii) anti-FcRn mAbs, two of the latest innovations in anti-FcRn mAbs leading to endogenous IgG depletion. We discuss the pharmacological effects, the biological consequences, and advantages of targeting IgG-FcRn interactions and their application in human therapeutics.


Subject(s)
Antibodies, Monoclonal , Receptors, Fc , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Histocompatibility Antigens Class I , Humans , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Receptors, Fc/metabolism , Tissue Distribution
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