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Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?

ABSTRACT: Broadly neutralizing antibodies directed against human immunodeficiency virus (HIV) offer promise as long-acting agents for prevention and treatment of HIV. Progress and challenges are discussed. Lessons may be learned from the development of monoclonal antibodies to treat and prevent COVID-19.

SUBMITTER: Caskey M

PROVIDER: S-EPMC10200322 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?

Caskey Marina M Kuritzkes Daniel R DR

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20221101 Suppl 4

Broadly neutralizing antibodies directed against human immunodeficiency virus (HIV) offer promise as long-acting agents for prevention and treatment of HIV. Progress and challenges are discussed. Lessons may be learned from the development of monoclonal antibodies to treat and prevent COVID-19. ...[more]

PMID: 36410387

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Project description:ObjectivePatients with immune-mediated diseases treated with anti-CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID-19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown.MethodsWe identified patients with immune-mediated diseases who received anti-CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction-confirmed COVID-19 between January 31, 2020, and January 31, 2021. General population comparators with COVID-19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti-CD20 monoclonal antibodies versus comparators were estimated by using Cox regression.ResultsWe identified 114 cases patients COVID-19 who had received anti-CD20 monoclonal antibodies for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). Patients treated with anti-CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03-4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62-1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36-1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti-CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID-19 diagnosis were excluded.ConclusionPatients who received anti-CD20 monoclonal antibodies for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti-CD20 monoclonal antibodies during the ongoing pandemic.

Project description:IntroductionThe last 12 years have seen remarkable progress in the isolation and characterization of at least five different epitope classes of HIV-specific broadly neutralizing antibodies (bnAbs). Detailed analyses of these bnAb lineages, maturation pathways and epitopes have created new opportunities for vaccine development. In addition, interest exists in passive administration of monoclonal antibodies as a viable option for HIV prevention.DiscussionRecently, two antibody-mediated prevention (AMP) trials of a passively administered monoclonal antibody targeting the HIV envelope CD4 binding site, called VRC01, provided proof-of-concept that monoclonal antibody infusion could offer protection against HIV acquisition. While the trials failed to show overall protection against HIV acquisition, sub-analyses revealed that VRC01 infusion provided a 75% prevention efficacy against HIV strains that were susceptible to the antibody. The study also demonstrated that in vitro neutralizing activity, measured by the TZM-bl/pseudovirus assay, was able to predict HIV prevention efficacy in humans. In addition, the AMP trials defined a threshold protective concentration, or neutralization titer, for the VRC01 class of bnAbs, explaining the observed low overall efficacy and serving as a benchmark for the clinical testing of new bnAbs, bnAb cocktails and neutralizing antibody-inducing vaccines. Newer bnAbs that exhibit greater potency and breadth of neutralization in vitro than VRC01 are available for clinical testing. Combinations of best-in-class bnAbs with complementary magnitude, breadth and extent of complete neutralization are predicted to far exceed the prevention efficacy of VRC01. Some engineered bi- and trispecific mAbs exhibit similar desirable neutralizing activity and afford advantages for manufacturing and delivery. Modifications that prolong the serum half-life and improve genital tissue persistence offer additional advantages.ConclusionsIterative phase 1 trials are acquiring safety and pharmacokinetic data on dual and triple bnAbs and bi- and trispecific antibodies in preparation for future AMP studies that seek to translate findings from the VRC01 efficacy trials and achieve acceptable levels of overall prevention efficacy.

Dataset Information

Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?

Publications

Monoclonal Antibodies as Long-Acting Products: What Are We Learning From Human Immunodeficiency Virus (HIV) and Coronavirus Disease 2019 (COVID-19)?

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