Evaluation of tixagevimab plus cilgavimab against SARS-CoV-2

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

Study: Neutralizing activity of Omicron BA.1 and BA.2 after pre-exposure prophylaxis with tixagevimab plus cilgavimab in vaccinated solid organ transplant recipients. Image Credit: Nhemz/Shutterstock

Background

Neutralizing antibody responses are reduced in most solid organ transplant recipients (SOTR) 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 anti-SARS-CoV-2 spike (S) receptor-binding domain (RBD)-associated antibody responses and plasma neutralizing ability against SARS-CoV-2 sublines. 2 Omicron 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. Participants were recruited in January 2022 for prior or planned administration of 150g tixagevimab plus 150g cilgavimab and March 2022 for administration of the T+C dose (300+300mg). All participants received a total dose of 300 + 300 mg between January 10 and April 4, 2022.

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

Plasma samples taken from the participants were also tested on anti-spike assays, including Roche Elecsys’ anti-SARS-CoV-2-S pan immunoglobulin Anti-Receptor Binding Domain (RBD) and diagnostic research assays at the meso scale. The tests assessed anti-nucleocapsid (anti-N) and anti-RBD binding antibodies. A chemiluminescent assay was also used to assess inhibition of angiotensin-converting enzyme-2 (ACE-2) receptor binding to the SARS-CoV-2 S protein. Samples were then tested against wild-type (WT) SARS-CoV-2, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and BA.1 and BA. 2 variants (Omicron).

The team collected electronic surveys seven days after each dose of T+C was administered to record any adverse events, particularly events related to cardiac and hypersensitivity reactions. The questionnaire also included questions regarding local symptoms such as pain, swelling, and redness, and systemic symptoms such as fatigue, myalgia, headache, fever, chills, diarrhea, and vomiting. . Symptoms were categorized by severity into mild symptoms that do not interfere with daily activities, moderate symptoms that interfere slightly with daily activities, or severe symptoms that interfere with daily activities. The team also defined breakthrough COVID-19 infections as new self-reported SARS-CoV-2 infection or anti-N seroconversion.

Results

Of the 61 study participants, 21 were treated with a single dose of 300+300 mg T+C while 40 received two doses of 150+150 mg T+C. The median age of the study cohort was 62.5 years with 59% women. Nearly 52% of participants received a kidney transplant and 26% had a chest transplant. Additionally, 52% of participants consumed triple immunosuppressants, including antimetabolites, calcineurin inhibitors, and corticosteroids.

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

After receiving a full dose of T+C, the median anti-RBD titer increased from 424 U/ml to 3500 U/ml. Additionally, 26% of participants who had no detectable antibodies prior to T+C administration seroconverted. The alteration in antibody titer was comparable in individuals injected with a single dose of 300 + 300 mg and two doses of 150 + 150 mg. The team also noted a similar change in antibody titer in people who were not recently exposed to a SARS-CoV-2 antigen.

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

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

*Important Notice

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

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