The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity and reliability, monoclonal antibodies (mAbs) have emerged as powerful tools to treat and detect numerous diseases. Hence, many researchers have begun to urgently develop Ab-based kits for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ab drugs for use as COVID-19 therapeutic agents. The detailed structure of the SARS-CoV-2 spike protein is known, and since this protein is key for viral infection, its receptor-binding domain (RBD) has become a major target for therapeutic Ab development. Because SARS-CoV-2 is an RNA virus with a high mutation rate, especially under the selective pressure of aggressively deployed prophylactic vaccines and neutralizing Abs, the use of Ab cocktails is expected to be an important strategy for effective COVID-19 treatment. Moreover, SARS-CoV-2 infection may stimulate an overactive immune response, resulting in a cytokine storm that drives severe disease progression. Abs to combat cytokine storms have also been under intense development as treatments for COVID-19. In addition to their use as drugs, Abs are currently being utilized in SARS-CoV-2 detection tests, including antigen and immunoglobulin tests. Such Ab-based detection tests are crucial surveillance tools that can be used to prevent the spread of COVID-19. Herein, we highlight some key points regarding mAb-based detection tests and treatments for the COVID-19 pandemic.

Monoclonal antibodies (mAbs) represent a major class of therapeutics with widespread clinical applications in oncology, immunology, hematology, neurology and infectious disease. Since the introduction of hybridoma technology in 1975, the field has been advanced by a succession of innovations including chimeric and humanized antibody engineering, phage display, transgenic mouse platforms and high-throughput single B cell isolation. These technological developments have enhanced the specificity, potency and safety of mAbs, resulting in 144 FDA-approved antibody drugs on the market and 1,516 worldwide candidates in clinical development as of August 2025. Engineering breakthroughs have led to new modalities of antibody-based therapeutics, such as antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor T (CAR-T) cell therapies. Each of these modalities has therapeutic utility across multiple disease domains. Recent advances in delivery strategies, notably mRNA-lipid nanoparticles (LNPs) and antibody-directed in vivo CAR-T cell reprogramming, can enable precision therapies while reducing off-target effects and manufacturing complexity. The integration of artificial intelligence (AI) and machine learning (ML), next-generation sequencing (NGS), and structural modeling tools has further accelerated antibody discovery, affinity maturation and immunogenicity prediction, allowing for more efficient and rational antibody design. The advances in antibody technology are reflected in the rapid market growth of antibody-based therapeutics, which had global sales exceeding USD 267 billion in 2024. This review provides a comprehensive update on recent developments in antibody discovery platforms, therapeutic formats and market trends, highlighting emerging strategies that are reshaping the landscape of antibody-based medicine. Furthermore, we discuss clinical translation, regulatory landscapes, and the integration of engineering, biology and informatics. Together, these aspects shape a dynamic and multidisciplinary future for the therapeutic antibody field, which is poised to address unmet clinical needs and global healthcare priorities.

Mitigation strategies of the coronavirus disease 2019 (COVID-19) pandemic have been greatly hindered by the continuous emergence of SARS-CoV-2 variants. New sensitive, rapid diagnostic tests for the wide-spectrum detection of viral variants are needed. We generated a panel of 41 monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein (NP) by using mice hybridoma techniques. Of these mAbs, nine exhibited high binding activities and were applied in latex-based lateral flow immunoassays (LFIAs). The LFIAs utilizing NP-mAb-7 and -40 had the best sensitivity and lowest limit of detection: 8 pg for purified NP and 625 TCID₅₀/mL for the authentic virus (hCoV-19/Taiwan/4/2020). The specificity tests showed that the NP-mAb-40/7 LFIA strips did not cross-react with five human coronavirus strains or 20 other common respiratory pathogens. Importantly, we found that 10 NP mutants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) variants, could be detected by NP-mAb-40/7 LFIA strips. A clinical study (n = 60) of the NP-mAb-40/7 LFIA strips demonstrated a specificity of 100% and sensitivity of 90% in infected individuals with cycle threshold (Ct) values < 29.5. These anti-NP mAbs have strong potential for use in the clinical detection of SARS-CoV-2 infection, whether the virus is wild-type or a variant of concern.

The COVID-19 pandemic continues to threaten human health worldwide, as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around K417 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC ₅₀ values that range from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on a broadly neutralizing chimeric antibody to create K-RBD-hAb-62, which still retains excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.

Since the emergence of severe acute respiratory syndrome coronavirus 2 Omicron, dramatic changes in the receptor-binding domain have allowed for virus escape from many therapeutic antibodies. Development of antibodies effective against current viral strains is, therefore, necessary to provide useful clinical treatments and can also yield fundamental information about viral neutralization. Here, we utilized single B-cell antibody technology to isolate and characterize neutralizing antibodies from splenocytes of mice immunized with mRNA-LNPs. With this approach, we identified five BA.5 and four XBB.1.5 neutralizing chimeric antibodies (ChAbs). The identified ChAbs, BA.5-ChAb-41, XBB.1.5-ChAb-17 and XBB.1.5-ChAb-26, each potently neutralized BA.5, XBB.1.5 and JN.1 pseudotype viruses with low IC ₅₀ (1.9, 2.3 and 10.93 ng ml ⁻¹ ). Furthermore, XBB.1.5-ChAb-26 showed neutralizing capability against the current JN.1-related variants, KP.3.1.1 and XEC. By performing single amino acid substitution of the receptor-binding motif (RBM), we observed that the epitopes of BA.5-ChAb-41 and XBB.1.5-ChAb-17 include Y453 and R498 in the RBM. Moreover, XBB.1.5-ChAb-26 epitope includes Y453 and T500, which may contribute to its ability to neutralize JN.1, KP.3.1.1 and XEC variants. In summary, our approach allowed us to efficiently screen for highly functional antibodies, and we further identified critical residues in the epitopes to aid in the design of therapeutic virus-neutralizing antibodies.