A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rapidly spreading worldwide. Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections. However, the emergence of SARS-CoV-2 variants of concern (VOCs), such as Delta (B.1.617.2) and the recently emerged Omicron (B.1.1.529), has seriously challenged the application of current therapeutics. Therefore, there is still a pressing need for identification of new broad-spectrum antivirals. Here, we further characterized a human antibody (58G6), which we previously isolated from a patient, with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations (IC50) of 1.69 ng/ml and 54.31 ng/ml, respectively. 58G6 shows prophylactic and therapeutic efficacy in hamsters challenged with the Delta and Omicron variants through nasal delivery. Notably, a very low dosage (2 mg/kg daily) of 58G6 efficiently prevented Omicron variant replication in the lungs. These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection. In general, 58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants. To the best of our knowledge, 58G6 is one of the most potent neutralizing antibodies against Omicron, with a broader spectrum than those approved for clinical use. 58G6 could be developed as a nebulized therapy, which would be more cost effective and user friendly and enhance the clinical outcome compared to that obtained with direct nasal delivery.

The latest Omicron BA.4 and BA.5 lineages are frowning toward COVID‐19 preventive measures: A threat to global public health

“…33 Studies showed that nasal delivery of a human antibody (58G6) provides protection against SARS‐CoV‐2 Delta and Omicron variants. 34 Nitric oxide nasal spray (NONS) may reduce symptoms, severity, and hospitalization rate among mild COVID‐19 patients. 35 Also, some studies recommended monoclonal antibodies (mAbs) for high‐risk ambulatory COVID‐19 patients for better outcomes.…”

“…These are paxlovid tablets (nirmatrelvir and ritonavir co‐packaged for oral use by Pfizer) and lagevrio (molnupiravir by Merck) 33 . Studies showed that nasal delivery of a human antibody (58G6) provides protection against SARS‐CoV‐2 Delta and Omicron variants 34 . Nitric oxide nasal spray (NONS) may reduce symptoms, severity, and hospitalization rate among mild COVID‐19 patients 35 .…”

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

“…Several studies have demonstrated the therapeutic efficacy of monoclonal antibody through inhalation in animal models of COVID-19 [42][43][44]. In one preclinical study, inhalation (nebulization) of 1212C2, a fully human monoclonal antibody derived from a COVID-19 patient, exhibited remarkable therapeutic efficacy in hamsters, and the inhalation route was more efficient than the systemic route (intraperitoneal) [42].…”

Vaccination using mutated receptor binding domains of SARS-CoV-2: Evidence for partial immune escape but not serotype formation

“…Neutralizing antibody 58G6, isolated from a convalescent patient, was found to recognize AA450-458 and 470-495 regions on RBD. Although it is able to neutralize Omicron BA.1, its efficacy is 40fold lower than wt neutralization (11). In addition to E484K, K417N is shown to abrogate RBD binding of many neutralizing antibodies (12).…”