Convalescent plasma post-vaccination increases binding and neutralizing antibodies against SARS-CoV-2 variants

A recent study published on the preprint server medRxiv* assesses the boost in antibodies against all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants post-vaccination in samples collected from previously infected coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donors.

Study: Vaccination of COVID-19 Convalescent Plasma Donors Increases Binding and Neutralizing Antibodies Against SARS-CoV-2 Variants. Image Credit: Pavel Kosolapov /


During the initial waves of the coronavirus disease 2019 (COVID-1)9 pandemic, effective therapies against the SARS-CoV-2 infection and COVID-19 were lacking. During that period, the medical community turned to use CCP obtained from recovered patients as passive immunotherapy for newly hospitalized patients.

However, observational studies and randomized controlled trials found that the beneficial effects of CCP are sparse. Eventually, as there were no significant beneficial effects, CCP use was discontinued early in 2021. Vaccination rollouts and the availability of monoclonal antibody (mAb) therapeutics helped in controlling SARS-CoV-2 infection and assisting in the recovery of the patients.

Moreover, the interest in CCP derived from vaccine-boosted CCP donors is resurging due to the emergence of new SARS-CoV-2 variants. The SARS-CoV-2 B.1.617.2

Delta variant is currently the primary circulating strain that is causing hospitalizations and deaths in unvaccinated patients, as well as breakthrough infections in vaccinated people. Notably, the Delta variant has been found to be resistant to neutralization by some mAbs.

Previous studies have reported that vaccination of previously infected individuals significantly boosts anti-SARS-CoV-2 antibody titers. When vaccinated, previously infected CCP donors may have higher antibody levels and a boosted immunity.

With this renewed interest in CCP, it is crucial to understand if vaccination of previously infected CCP or regular allogeneic donors will provide CCP units with enhanced efficacy, including against the rapidly spreading SARS-CoV-2 variants of concern (VOCs). Moreover, the effect of vaccination on antibodies obtained from previously infected CCP donors against rapidly spreading SARS-CoV-2 VOCs is still under investigation.

Study design

In the current study, samples were collected from 11 previously infected CCP donors, between January and March 2021 before and after vaccination. The researchers tested these samples to measure binding antibody levels and neutralization activity against the ancestral Wuhan-Hu-1 SARS-CoV-2 strain, as well as several variants including the B.1.1.7, B.1.351, P.1, D614G, B.1.617.2, and B.1.427 strains.

Several assays were performed to measure the levels of total immunoglobulin (Ig) and IgG antibodies against the S1 domain of the SARS-CoV-2 spike antigen, in vitro binding and angiotensin-converting enzyme 2 (ACE2) inhibition against S1, nucleocapsid (N), and receptor-binding domain (RBD) proteins, and neutralization titers. Several additional tests were conducted to assess the binding and neutralization activity against different SARS-CoV2 S1 variants including the B.1.1.7 (Alpha), B.1.351 (Beta), P.1-gamma, D614G, B.1.617 (Delta), and B.1.427 (Epsilon) strains.

Findings of the study

The researchers found that the antibody levels were significantly lower before vaccination than after vaccination. While the post-vaccination samples had an increased concentration for the anti-spike and anti-RBD binding antibodies, the levels sightly decreased for the anti-N antibodies.

ACE2 inhibition results also showed a similar pattern. After a natural infection, the samples showed low neutralization activity against each of the variants. However, post-vaccination, there was a remarkable rise of 4- to 7- fold in all variants. The researchers reported that ACE2 inhibitory activity of the antibodies following vaccination of the CCP donors against all variants was 67.90% ± 10.74.

Using the variant-specific spike Reporter Viral Particle Neutralization (RVPN) on the pre-and post-vaccination samples, the researchers measured the ability to inhibit viral entry. To this end, lentivirus-based vectors of renilla luciferase RVPs, which were bearing the Spike from the ancestral strain Wuhan-Hu-1, B.1.1.7, B.1.351, P.1, B.1.1.7+E484K, B.1.617.2, and B.1.427 were used and titrated on 293T/ACE2/TMPRSS2 cells.

The variant-specific RVPN assay demonstrated neutralizing activity due to natural infection that was significantly higher for the Wuhan-Hu-1 strain than the B1.1.7+

E484K, B.1.351, and B.617.2 strains. The 50% neutralization titer (NT50) for the Wuhan-Hu-1 strain was 547, whereas the average NT50 following vaccination was 10,831 ± 2,000.

Thus, pre-vaccination CCP donor samples neutralized the ancestral Wuhan-Hu-1 more than any other variants, with the after-vaccination samples neutralizing all variants in a similar manner.


The researchers assessed the ability of vaccination to boost anti-SARS-CoV-2 antibody levels in previously infected CCP donors. Importantly, the researchers also determined the activity against the SARS-CoV-2 ancestral strain and VOCs.

The current study confirms that vaccination highly boosts natural immunity and also protects against reinfection, especially from variants. Because the neutralizing antibodies are correlates of protection for the SARS-CoV-2, the findings from this study demonstrate that the antibodies elicited by previous infection and vaccination are able to neutralize new variants in vitro.

*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.

Journal reference:
Dr. Ramya Dwivedi

Written by

Dr. Ramya Dwivedi

Ramya has a Ph.D. in Biotechnology from the National Chemical Laboratories (CSIR-NCL), in Pune. Her work consisted of functionalizing nanoparticles with different molecules of biological interest, studying the reaction system and establishing useful applications.


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