Evaluating tixagevimab plus cilgavimab against SARS-CoV-2

In a recent study posted to the medRxiv* preprint server, researchers assessed the neutralizing activity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant after tixagevimab plus cilgavimab (T+C) administration.

Background

Neutralizing antibody responses are lowered in most solid organ transplant recipients (SOTRs) even after receiving the coronavirus disease 2019 (COVID-19) vaccination. Various studies have reported the potential of administering a combination of monoclonal antibodies tixagevimab and cilgavimabas, a pre-exposure prophylactic (PrEP) measure, against the SARS-CoV-2 Omicron variant.   

About the study

In the present study, researchers analyzed antibody responses associated with the anti-SARS-CoV-2 spike (S) receptor-binding domain (RBD) and the plasma neutralizing capacity against SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in COVID-19 vaccinated SOTRs.

The team enrolled SOTRs in a nationwide, prospective observational study that recorded responses to the SARS-CoV-2 vaccine. The participants were recruited in January 2022 to inform the prior or planned administration of 150 g tixagevimab plus 150 g cilgavimab and in March 2022 for the administration of T+C (300+300 mg) dosage. All participants received a total dose of 300+300 mg between 10 January and 4 April 2022.

The team classified the eligible participants based on the history of exposure to the SARS-CoV-2 antigen which was defined as the receipt of a COVID-19 vaccine within 30 days before the first T+C injection and the first date of sample collection. Whole blood samples were obtained from the participants two weeks or lesser before and two weeks after each T+C dose.

Plasma samples collected from the participants were also tested on anti-spike assays including the Roche Elecsys anti-SARS-CoV-2-S anti-receptor binding domain (RBD) pan immunoglobulin and the Meso scale diagnostic research assays. The assays evaluated the anti-nucleocapsid (anti-N) and anti-RBD binding antibodies. A chemiluminescent assay was also used to evaluate the inhibition of angiotensin-converting enzyme-2 (ACE-2) receptor binding to the SARS-CoV-2 S protein. Samples were further assayed against the SARS-CoV-2 wild-type (WT), B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and BA.1 and BA.2 (Omicron) variants.

The team collected electronic surveys seven days after each T+C dose administration to record any adverse events, particularly events related to cardiac and hypersensitivity reactions. The questionnaire also included queries regarding local symptoms such as pain, swelling, and redness, and systemic symptoms such as fatigue, myalgia, headache, fever, chills, diarrhea, and vomiting. The symptoms were classified based on severity as mild symptoms that do not interfere with everyday activities, moderate symptoms that have slight interference in everyday activities, or severe symptoms that prevent everyday activities. The team also defined breakthrough COVID-19 infections as either self-reported new SARS-CoV-2 infection or anti-N seroconversion.          

Results

Among the 61 study participants, 21 were treated with a single dose of 300+300 mg T+C while 40 received two doses of 150+150mg T+C doses. The median age of the study cohort was 62.5 years with 59% females. Almost 52% of the participants were recipients of a kidney transplant and 26% had a thoracic transplant. Also, 52% of the participants consumed triple immunosuppressives, including antimetabolite, calcineurin inhibitor, and corticosteroids.

Furthermore, all the participants were vaccinated with at least three vaccine doses before T+C treatment including 38 individuals who had received four doses and five individuals who had received five doses. All participants received either BNT162b2, messenger ribonucleic acid (mRNA)-1273, or Ad.26.COV2.S COVID-19 vaccines as their third dose. Among the 22 individuals who were exposed to a SARS-CoV-2 antigen, 16 were vaccinated less than 30 days before T+C treatment, three were vaccinated after T+C receipt, and three were diagnosed with COVID-19 less than 90 days before T+C injection.

After receiving a full dose of T+C, median anti-RBD titer rose from 424 U/ml to 3500 U/ml. Moreover, 26% of the participants that did not have any detectable antibody before T+C administration displayed seroconversion. The alteration in the antibody titer was comparable in individuals injected with a single 300+300mg dose and two 150+150mg doses. The team also noted a similar change in antibody titer among individuals who were not recently exposed to a SARS-CoV-2 antigen.

The neutralizing inhibition against the SARS-CoV-2 WT strain increased from 46% before T+C administration to 100% after administration. Moreover, the neutralizing inhibition increased from 44% to 100% against the Alpha, 26% to 100% against the Beta, and 39% to 100% against the Delta variant after the T+C injection. The team also observed a moderate positive association of anti-RBD titer with ACE2 inhibition against the WT, Alpha, Beta, and Delta variants. Furthermore, the team noted that SOTRs with neutralizing inhibition also had high anti-RBD titers following a T+C injection.

Overall, the study findings showed that T+C effectively increased the neutralizing capacity of SOTRs against SARS-CoV-2 variants, The researchers believe that future studies can investigate the durability of the neutralization induced against emerging viral variants. 

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.