Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation

Quandt, Jasmin; Muik, Alexander; Salisch, Nadine; Lui, Bonny Gaby; Lutz, Sebastian; Krueger, Kimberly; Wallisch, Ann-Kathrin; Adams‐Quack, Petra; Bacher, Maren; Finlayson, Andrew; Ozhelvaci, Orkun; Vogler, Isabel; Grikscheit, Katharina; Hoehl, Sebastian; Goetsch, Udo; Ciesek, Sandra; Tuereci, Oezlem; Şahin, Uğur

doi:10.1101/2022.04.01.486695

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…Moreover, several studies reported stem-directed antibody- mediated protection against H5N1 and H7N9 zoonotic influenza strains through hemagglutinin imprinting during childhood resulting from exposure to seasonal H1N1 and H3N2, respectively ( 48, 50 ). Similarly, we show that exposure to the antigenically shifted Omicron primarily leads to a recall of existing memory B cells specific for epitopes shared by multiple SARS-CoV-2 variants rather than by priming naïve B cells recognizing Omicron-specific epitopes (at least up to 100 days post breakthrough infection), as also recently reported ( 51 ). Although immune imprinting may be beneficial in stimulating responses to cross-reactive SARS-CoV-2 epitopes, antibody responses to some Omicron-specific epitopes were markedly diminished by prior antigenic exposure.…”

Section: Discussionsupporting

confidence: 87%

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Park

Pinto

Walls

et al. 2022

Preprint

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SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

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Section: Discussionsupporting

confidence: 87%

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Park

Pinto

Walls

et al. 2022

Preprint

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“…Indeed, it is worth noting that Omicron breakthrough infection mediates a robust B-cell recall response, expanding preformed memory B cells that recognize the epitopes shared by different variants [ 23 , 24 ]. It has been reported that the preformed B-cell memory pool has sufficient plasticity to be remodeled by exposure to heterologous S protein, allowing the effective neutralization of other variants [ 25 ]. Therefore, we consider that breakthrough infection with Omicron could enrich the memory B-cell plateaus of vaccinated individuals and recall preexisting B cells, which recognize the conserved S protein epitopes and provide cross-protection.…”

Section: Discussionmentioning

confidence: 99%

Omicron Infection Evokes Cross-Protection against SARS-CoV-2 Variants in Vaccinees

et al. 2022

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Due to the rapid global spread of the Omicron (B.1.1.529) variant, efforts to scale up COVID-19 booster vaccination have been improved, especially in light of the increasing evidence of reduced neutralizing antibody (NT Ab) over time in vaccinated subjects. In this study, neutralizing antibody responses against the Wild-Type, Delta, and Omicron strains were evaluated among vaccinees, both infected with Omicron or uninfected, and non-vaccinated subjects infected with Omicron. The aim of the study was to compare the cross-protective humoral response to the variant strains induced by vaccination and/or Omicron infection. The results showed a significant difference in the neutralizing antibody response between the vaccinees and the Omicron-infected vaccinated subjects against the three tested strains (p < 0.001), confirming the booster effect of the Omicron infection in the vaccinees. By contrast, Omicron infection only did not enhance the antibody response to the other variants, indicating a lack of cross-protection. These results suggest the importance of updating the current formulation of the SARS-CoV-2 vaccine to protect people against the Omicron subvariants. A specific Omicron vaccine, administered as a booster for the previously adopted mRNA vaccines, may protect against a wider range of SARS-CoV-2 variants. However, it is unlikely that the Omicron vaccine alone would be able to protect non-vaccinated subjects against other circulating variants.

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“…In several studies, hybrid immunity resulting from infection-acquired immunity boosted with vaccination conferred the strongest, or longer-lasting protection, respectively [33, 34]. Similarly, Omicron break-through infections in previously vaccinated individuals have been shown to drive cross-variant neutralization and memory B cell formation [35], suggesting that a combination of both, natural infection and vaccination, will have more impact on the future COVID-19 epidemiology than one of the events alone.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Estimating the distribution of COVID-19-susceptible, -recovered, and -vaccinated individuals in Germany up to April 2022

Maier

Rose

Burdinski

et al. 2022

Preprint

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After having affected the population for two years, the COVID-19 pandemic has reached a phase where a considerable number of people in Germany have been either infected with a SARS-CoV-2 variant, vaccinated, or both. Yet the full extent to which the population has been in contact with either virus or vaccine remains elusive, particularly on a regional level, because (a) infection counts suffer from under-reporting, and (b) the overlap between the vaccinated and recovered subpopulations is unknown. Since previous infection, vaccination, or especially a combination of both reduce the risk of severe disease, a high share of individuals with SARS-CoV-2 immunity lowers the probability of severe outbreaks that could potentially overburden the public health system once again, given that emerging variants do not escape this reduction in susceptibility. Here, we estimate the share of immunologically naïve individuals by age group for each of the 16 German federal states by integrating an infectious disease model based on weekly incidences of SARS-CoV-2 infections in the national surveillance system and vaccine uptake, as well as assumptions regarding under-ascertainment. We estimate a median share of 7.0% of individuals in the German population have neither been in contact with vaccine nor any variant as of March 31, 2022 (quartile range [3.6%– 9.8%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.5% [1.3%–5.5%] for ages 18–59 and 4.3% [2.7%–5.8%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.1% [14.0%–17.8%] of the population in Germany, across all ages, are estimated to be immunologically naïve, highlighting the large impact the Omicron wave had until the beginning of spring in 2022.

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Omicron breakthrough infection drives cross-variant neutralization and memory B cell formation

Cited by 9 publications

References 35 publications

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Omicron Infection Evokes Cross-Protection against SARS-CoV-2 Variants in Vaccinees

Estimating the distribution of COVID-19-susceptible, -recovered, and -vaccinated individuals in Germany up to April 2022

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