Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

Winklmeier, Stephan; Eisenhut, Katharina; Taskin, Damla; Rübsamen, Heike; Schneider, Celine; Eichhorn, Peter; Ot, Keppler; Klein, Michelle; Mader, Simone; Kümpfel, Tania; Meinl, Edgar

doi:10.1101/2021.05.15.21257210

Cited by 6 publications

(5 citation statements)

References 86 publications

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“…Following primary immunization, individuals with preexisting immunity showed increased titers of all antibodies except IgG3 against WT and VOCs, when compared to SARS-CoV-2 naïve subjects. Our data were consistent with recent studies that reported the presence of pre-existing SARS-CoV-2-specific and cross-variant specific-memory B cells in COVID-19 recovered subjects (16,17,19,20,35). In line with our results, a recent report showed a strong correlation between the frequency of SARS-CoV-2-specific memory B cells at baseline and the antibody concentrations following vaccination (6).…”

Section: Discussionsupporting

confidence: 93%

The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity

et al. 2021

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mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.

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Section: Discussionsupporting

confidence: 93%

The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity

et al. 2021

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“…These findings were supported by another study by Winkmeier et al, who assessed cross-variant memory-Bcell responses among 16 convalescent patients and found that memory-B-cell-derived IgGs recognized the RBD of B.1.1.7 similarly to the wild-type, while reactivity to B.1.351 and P.1. decreased by 30% and 50%, respectively (86). Taken together, despite declining antibody titers, memory B cells with broad cross-reactivity have been shown to persist up to 1 year after natural infection and are capable of producing nAbs against wild type and variant RBDs.…”

Section: Role Of Memory B Cellmentioning

confidence: 96%

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

2021

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.

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“…Longitudinal analyses have also found that SARS-CoV-2-reactive memory B cell clones are stably maintained in convalescent COVID-19 patients for several months following infection [30, 45]. Memory B cell responses persist despite the natural decline of SARS-CoV-2-specific IgG binding titers, suggestive of high-quality and durable memory B cell responses [46].…”

Section: Discussionmentioning

confidence: 99%

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

Walters

Schouest

Patel

et al. 2021

Preprint

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SUMMARYThe enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.

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Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

Cited by 6 publications

References 86 publications

The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity

The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

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