Evaluation of tixage vimab and cilgavimab for SARS-CoV-2

In a recent study posted on medRxiv* Preprint server, researchers evaluated neutralizing activity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant after administration of tixagebimab and cilgavimab (T + C).

Background

Neutralizing antibody Even after being vaccinated against Coronavirus Disease 2019 (COVID-19), most solid organ transplant recipients (SOTRs) are less responsive. Various studies have reported the possibility of administering the monoclonal antibody tixagebimab to the SARS-CoV-2 omicron variant with a combination of pre-exposure prophylaxis (PrEP) measures sirgabimabus.

About research

In this study, researchers analyzed antibody reactions associated with the anti-SARS-CoV-2 spike (S) receptor binding domain (RBD) and plasma against SARS-CoV-2 omicron subline BA.1 and BA.2. The neutralizing ability was analyzed. With COVID-19 vaccination SOTR.

The team enrolled SOTR in a national prospective observational study recording responses to the SARS-CoV-2 vaccine. Participants will be notified of pre- or planned doses of 150 g tixagebimab and 150 g cilgavimab in January 2022, and for the administration of T + C (300 + 300 mg) doses in March 2022. Was recruited for. All participants received a total dose of 300 + 300 mg between January 10th and April 4th, 2022.

The team categorized eligible participants based on their history of exposure to SARS-CoV-2. antigen This was defined as receipt of the COVID-19 vaccine within 30 days prior to the first T + C injection and the first date of sample collection. Whole blood samples were taken from participants within and 2 weeks after each T + C dose.

Plasma samples collected from participants were also tested in anti-spikes assays, including Rocheelexis anti-SARS-CoV-2-S anti-receptor binding domain (RBD) pan-immunoglobulin and mesoscale diagnostic study assays. The assay evaluated anti-nucleocapsid (anti-N) and anti-RBD binding antibodies. The chemiluminescence assay was also used to assess inhibition of the angiotensin converting enzyme-2 (ACE-2) receptor that binds to the SARS-CoV-2 S protein. Samples are further assayed for SARS-CoV-2 wild-type (WT), B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and BA.1. it was done. 2 (Omicron) variant.

The team collected electronic studies 7 days after each T + C dose to record adverse events, especially those associated with cardiac and hypersensitivity reactions. Questions also included questions about local symptoms such as pain, swelling, and redness, as well as systemic symptoms such as fatigue, muscle aches, headaches, fever, chills, diarrhea, and vomiting. Symptoms were classified according to their severity into mild symptoms that do not interfere with daily life, moderate symptoms that slightly interfere with daily life, and severe symptoms that interfere with daily life. The team also defined the breakthrough COVID-19 infection as either a new self-reported SARS-CoV-2 infection or an anti-N seroconversion.

result

Of the 61 study participants, 21 were treated with a single dose of 300 + 300 mg T + C and 40 received two doses of 150 + 150 mg T + C. The median age of the study cohort was 62.5 years, with 59% being female. Almost 52% of the participants had a kidney transplant and 26% had a chest transplant. In addition, 52% of participants took three immunosuppressive drugs, including antimetabolites, calcineurin inhibitors, and corticosteroids.

In addition, all participants received at least 3 vaccinations prior to T + C treatment. This includes 38 people who received 4 doses and 5 people who received 5 doses. All participants received either BNT162b2, messenger ribonucleic acid (mRNA) -1273, or Ad.26.COV2.SCOVID-19 vaccine as the third dose. Of the 22 exposed to SARS-CoV-2 antigen, 16 were vaccinated within 30 days of T + C treatment, 3 were vaccinated after receiving T + C, and 3 were less than 90 days. I was diagnosed with COVID-19. Before T + C injection.

After administration of the full dose of T + C, the median anti-RBD titer increased from 424 U / ml to 3500 U / ml. In addition, 26% of participants who did not have detectable antibodies prior to T + C administration showed seroconversion.Change Antibody titer Equivalent in individuals injected with a single dose of 300 + 300 mg and two doses of 150 + 150 mg. The team also noticed similar changes in antibody titers among individuals who have not recently been exposed to the SARS-CoV-2 antigen.

Neutralization inhibition for the SARS-CoV-2 WT strain increased from 46% before T + C to 100% after administration. In addition, neutralization inhibition increased from 44% to 100% for alpha, 26% to 100% for beta, and 39% to 100% for delta variants after T + C infusion. The team also observed a modest positive association between ACE2 inhibition and anti-RBD titers for WT, alpha, beta, and delta mutants. In addition, the team noted that SOTR with neutralization inhibition also showed high anti-RBD titers after T + C injection.

Overall, the study results showed that T + C effectively increased the ability of SOTR to neutralize SARS-CoV-2 mutants. Researchers believe that future studies will be able to investigate the persistence of neutralization induced against new viral variants.

*Important Notices

medRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.