Vaccination of COVID‐19 convalescent plasma donors increases binding and neutralizing antibodies against SARS‐CoV‐2 variants

Abstract

Background COVID‐19 convalescent plasma (CCP) was widely used as passive immunotherapy during the first waves of SARS‐CoV‐2 infection in the US. However, based on observational studies and randomized controlled trials, the beneficial effects of CCP were limited, and its use was virtually discontinued early in 2021, in concurrence with increased vaccination rates and availability of monoclonal antibody (mAb) therapeutics. Yet, as new variants of the SARS‐CoV‐2 spread, interest in CCP derived from vaccine‐boosted CCP donors is resurging. The effect of vaccination of previously infected CCP donors on antibodies against rapidly spreading variants is still under investigation. Study design/methods In this study, paired‐samples from 11 CCP donors collected before and after vaccination was tested to measure binding antibody levels and neutralization activity against the ancestral Wuhan‐Hu‐1 and SARS‐CoV‐2 variants (Wuhan‐Hu‐1 with D614G, alpha, beta, gamma, delta, epsilon) on the Ortho Vitros Spike Total Ig and IgG assays, the MSD V‐PLEX SARS‐CoV‐2 arrays for IgG binding and ACE2 inhibition, and variant‐specific Spike Reporter Viral Particle Neutralization (RVPN) assays. Results/findings Binding and neutralizing antibodies were significantly boosted by vaccination, with several logs higher neutralization for all the variants tested post‐vaccination compared to the pre‐vaccination samples, with no difference found among the individual variants. Discussion Vaccination of previously infected individuals boosts antibodies including neutralizing activity against all SARS‐CoV‐2 variants.

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

“…IVIG, a standard treatment for many people with PIs, and COVID-19 convalescent plasma can both provide protection to people with PI. Studies have shown that both IVIG and COVID-19 convalescent plasma now have increased anti-SARS-CoV2 antibody titers compared with early trials because of vaccine coverage, which generated higher antibody titers than infection in the general population, including plasma donors [ 81 ]. Some studies suggest that convalescent plasma can be especially beneficial for people with PI, helping avoid relapses and prolonged infection [ 42 , 58 ].…”

Analysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

“…Efficacy outcomes have been mixed to date, with most failures explained by low dose, late usage, or both, but efficacy of high-titer CCP has been definitively proven in outpatients with mild disease stages 6 , 7 . Neutralizing antibody (nAb) efficacy against VOC remains a prerequisite to support CCP usage, which can now be collected from vaccinated convalescents, including donors recovered from breakthrough infections (so-called “hybrid plasma” or “Vax-CCP”) 8 : pre-Omicron evidence suggest that those nAbs have higher titers and are more effective against VOCs than those from unvaccinated convalescents 9 , 10 . From a regulatory viewpoint, to date, plasma from vaccinees that have never been convalescent does not fall within the FDA emergency use authorization.…”

Neutralizing antibody levels against SARS‐CoV‐2 variants of concern Delta and Omicron in vaccine breakthrough‐infected blood donors

“…9,10 While clinical correlates for high neutralizing antibody (nAb) titers in CCP exist, most studies have been run in the prevaccine era. 11 Although Di Germanio et al recently reported boosting of anti-SARS-CoV-2 titers in 11 CCP donors after mRNA COVID19 vaccination, 12 kinetics of Omicron-specific nAb titers have been poorly investigated so far. In particular, the opposite sequence, that is, the effect of SARS-CoV-2 breakthrough infection on nAb titer in previously vaccinated CCP donors, has never been explored.…”