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Neutralizing antibodies for the prevention and treatment of COVID-19.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus-cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

SUBMITTER: Du L

PROVIDER: S-EPMC8424621 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Neutralizing monoclonal antibodies for COVID-19 treatment and prevention.

Project description:The SARS-CoV-2 pandemic has caused unprecedented global health and economic crises. Several vaccine approaches and repurposed drugs are currently under evaluation for safety and efficacy. However, none of them have been approved for COVID-19 yet. Meanwhile, several nMAbs targeting SARS-CoV-2 spike glycoprotein are in different stages of development and clinical testing. Preclinical studies have shown that cocktails of potent nMAbs targeting the receptor binding site of SARS-CoV-2, as well as broad-nMAbs targeting conserved regions within the virus spike, might be effective for the treatment and prophylaxis of COVID-19. Currently, several clinical trials have started to test safety, tolerability, PKs and efficacy of these nMAbs. One paramount limitation for the use of nMAbs in clinical settings is the production of large amounts of MAbs and the high costs related to it. Cooperation among public and private institutions coupled with speed of development, rapid safety evaluation and efficacy, and early planning for scale-up and manufacture will be critical for the control of COVID-19 pandemic.

| S-EPMC7685954 | biostudies-literature

Neutralizing monoclonal antibodies for treatment of COVID-19.

Project description:Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.

| S-EPMC8054133 | biostudies-literature

Neutralizing antibodies for the treatment of COVID-19.

Project description: Not available

| S-EPMC7891858 | biostudies-literature

Broadly neutralizing antibodies against COVID-19.

Project description:The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions of infections and millions of deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since SARS-CoV-2 emerged, a variety of strains have acquired increasing numbers of mutations to gain increased transmissibility and escape from the immune response. Most reported neutralizing human mAbs, including all approved therapeutic ones, have been knocked down or out by these mutations. Broadly neutralizing mAbs are therefore of great value, to treat current and possible future variants. Here, we review four types of neutralizing mAbs against the spike protein with broad potency against previously and currently circulating variants. These mAbs target the receptor-binding domain, the subdomain 1, the stem helix, or the fusion peptide. Understanding how these mAbs retain potency in the face of mutational change could guide future development of therapeutic antibodies and vaccines.

| S-EPMC10301462 | biostudies-literature

Tackling COVID-19 with neutralizing monoclonal antibodies.

Project description:Monoclonal antibodies (mAbs) have revolutionized the treatment of several human diseases, including cancer and autoimmunity and inflammatory conditions, and represent a new frontier for the treatment of infectious diseases. In the last 20 years, innovative methods have allowed the rapid isolation of mAbs from convalescent subjects, humanized mice, or libraries assembled in vitro and have proven that mAbs can be effective countermeasures against emerging pathogens. During the past year, an unprecedentedly large number of mAbs have been developed to fight coronavirus disease 2019 (COVID-19). Lessons learned from this pandemic will pave the way for the development of more mAb-based therapeutics for other infectious diseases. Here, we provide an overview of SARS-CoV-2-neutralizing mAbs, including their origin, specificity, structure, antiviral and immunological mechanisms of action, and resistance to circulating variants, as well as a snapshot of the clinical trials of approved or late-stage mAb therapeutics.

| S-EPMC8152891 | biostudies-literature

Tackling COVID-19 with neutralizing monoclonal antibodies.

Project description: Not available

| S-EPMC8375150 | biostudies-literature

Broadly neutralizing antibodies for the treatment and prevention of HIV infection.

Project description:Purpose of reviewSeveral anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency, and targeting different HIV-1 envelope epitopes have entered clinical trials. bNAbs are being evaluated for their potential as long-acting alternatives to antiretrovirals in HIV-1 prevention and therapy, and for potential role in strategies aiming at long-term viral remission. Here, we discuss recent findings from bNAb clinical studies.Recent findingsbNAbs targeting distinct HIV-1 envelope epitopes have shown, in general, favorable safety profiles, and engineered bNAb variants have demonstrated improved pharmacokinetics. Single bNAb infusions transiently decreased viremia with subsequent selection of escape variants, while a combination of two bNAbs successfully maintained viral suppression in individuals harboring antibody-sensitive viruses after antiretroviral therapy (ART) was discontinued. Studies in animal models suggest that bNAbs can modulate immune responses and potentially interfere with the establishment or composition of the latent reservoir, and ongoing clinical studies aim to assess potential bNAb-mediated effects on HIV-1 persistence and host immune responses.SummaryEarly clinical studies support additional evaluation of bNAbs. Antibodies may offer advantages over standard ART for HIV-1 prevention and therapy, and as components of immunologic strategies to achieve sustained virologic control. The evaluation of engineered bNAbs with multispecificity, extended half-lives and increased potency, as well as alternative bNAb-delivery systems are being pursued.

| S-EPMC7340121 | biostudies-literature

COVID-19 neutralizing antibodies predict disease severity and survival.

Project description:COVID-19 exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, and high anti-RBD antibody levels. While anti-RBD IgG levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting protection from reinfection by this strain. However, SARS-CoV-2 sera was unable to cross-neutralize a highly-homologous pre-emergent bat coronavirus, WIV1-CoV, that has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

| S-EPMC7587842 | biostudies-literature

COVID-19-neutralizing antibodies predict disease severity and survival.

Project description:Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

| S-EPMC7837114 | biostudies-literature

COVID-19 reinfection in the presence of neutralizing antibodies.

Project description:After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.

| S-EPMC7928639 | biostudies-literature

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