Plasma from vaccinated and COVID-19 convalescent subjects as passive immunotherapy against the new Omicron BQ.1.1, XBB, and BF.7 variants

By Tarun Sai LomteNov 30 2022Reviewed by Danielle Ellis, B.Sc.

In a recent study posted to bioRxiv*, researchers systematically reviewed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BQ.1.1 neutralization data from individual patient samples.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Antivirals and passive immunotherapies are often required to treat coronavirus disease 2019 (COVID-19) and clear high SARS-CoV-2 load in immunocompromised (IC) patients. High, persistent, and chronic SARS-CoV-2 viral loads elevate the risk of mutations and transmission. All monoclonal antibodies (mAbs) authorized for preventive or therapeutic use have been inefficacious against SARS-CoV-2 Omicron.

COVID-19 convalescent plasma (CCP) contains thousands of unique antibody specificities of multiple isotypes, many of which can neutralize SARS-CoV-2. Plasma from vaccinated and infected individuals (VaxCCP) can neutralize pre-Omicron and Omicron variants (BA.1 to BA.4/5).

The study and findings

In the present study, researchers systematically reviewed the literature for data on the neutralization of SARS-CoV-2 Omicron BQ.1.1 by plasma obtained from vaccinated individuals with or without past SARS-CoV-2 infection or those infected recently with Omicron. PubMed, bioRxiv, and medRxiv were searched for research papers reporting BQ.1.1 neutralization.

Articles published in the English language were eligible for inclusion. The researchers extracted data on the type of neutralization assay, sampling interval, geometric mean neutralizing titers (GMT₅₀), and minimum and maximum neutralizing dilutional titers of SARS-CoV-2 WA1 and Omicron sub-lineages from eligible studies.

Seven studies were identified that reported the neutralization of SARS-CoV-2 WA1 and Omicron (BQ.1.1, BF.7, BA.4/5, XBB, and BA.4.6) with live or pseudovirus neutralization assays. These studies cumulatively covered 652 patients. Four studies used live-virus neutralization assays in different cell types, and three implemented lentiviral pseudovirus assays with diverse spike proteins.

One study primarily involved individuals with BA.1 or BA.4/5 breakthrough infections and healthcare workers boosted with a monovalent vaccine in the United States (US). The second study sampled triple-vaccinated subjects in the US before and after receiving a fourth vaccine dose, regardless of their prior infection status.

Another study in the US involved participants with no documented history of COVID-19 and sampled them before and after the third vaccination and after the fourth dose with a bivalent/monovalent vaccine. A Chinese study examined BQ.1.1 neutralization activity in four cohorts after three CoronaVac doses without COVID-19 or after infection with Omicron BA.1, BA.2, or BA.4/5.

A US study examined the neutralizing activity of samples after three or four vaccinations with those receiving a bivalent vaccine for the fourth dose with or without COVID-19 history. A French analysis examined plasma specimens four and 16 weeks after the third mRNA vaccination and 12 to 32 weeks after breakthrough infection with BA.1, BA.2, or BA.5 variant.

The last study conducted in the US examined samples after the third vaccination with a monovalent dose and the fourth dose with a monovalent or bivalent vaccine. Subjects across the studies were categorized into three groups – 1) vaccine boosted and had COVID-19 (boosted VaxCCP), 2) boosted but self-reported SARS-CoV-2-naïve or were negative for antibodies against nucleocapsid, and 3) Omicron-infected but unvaccinated.

Boosted VaxCCP samples neutralized Omicron XBB, BQ.1.1, and BF.7 variants with two/three times the dilutional potency of vaccinated, CCP, or pre-boost vaccination plasma samples. More than 97% of boosted VaxCCP specimens neutralized Omicron BQ.1.1, XBB, and BF.7, despite the 25-fold lower neutralizing potency against BQ.1.1 relative to the WA1 strain.

The GMT₅₀ for WA1 was 80 with pre-Alpha CCP, whereas it was 83 for BQ.1.1 variant with boosted plasma samples. Four studies examined BQ.1.1 neutralization in individuals boosted with a bivalent mRNA vaccine (wildtype + BA.4/5 spike). Sixty-nine plasma samples (92%) neutralized BQ.1.1 within four weeks of bivalent booster administration.

Several studies assessed the virus-neutralizing activity of samples collected before the third or fourth vaccine dose, administered six to 11 months after the last dose. These samples had four times lower GMT₅₀ than VaxCCP but showed similar fold reductions. The live-virus neutralization assays for VaxCCP had, in general, 10-fold higher neutralizing antibody (nAb) levels. In contrast, the GMT₅₀ in COVID-19-naïve boosted plasma samples was slightly higher with the pseudovirus assays than with live virus assays.

Conclusions

In summary, boosted VaxCCP neutralized more than 95% of SARS-CoV-2 Omicron BQ.1.1, BF.7, and XBB. Samples collected within a six-month window from boosted individuals without prior infection had half the nAb levels as VaxCCP specimens. Taken together, boosted VaxCCP could be a viable substitute for anti-SARS-CoV-2 mAbs for passive immunotherapy of IC patients. The researchers suggested revising guidelines to include boosted VaxCCP for COVID-19 treatment in IC patients.

*Important notice: bioRxiv 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.