Vaccine Breakthrough Infection with the SARS-CoV-2 Delta or Omicron (BA.1) Variant Leads to Distinct Profiles of Neutralizing Antibody Responses

Seaman, Michael S.; Siedner, Mark J.; Boucau, Julie; Lavine, Christy L.; Ghantous, Fadi; Liew, May Y.; Mathews, Josh; Singh, Arshdeep; Marino, Caitlin; Regan, James; Uddin, Rockib; Choudhary, Manish; Flynn, James P.; Chen, Geoffrey; Stuckwisch, Ashley; Lipiner, Taryn; Kittilson, Autumn; Melberg, Meghan; Gilbert, Rebecca F; Reynolds, Zahra; Iyer, Surabhi; Chamberlin, Grace; Vyas, Tammy D.; Vyas, Jatin M.; Goldberg, Marcia B.; Luban, Jeremy; Li, Jonathan Z.; Barczak, Amy K.; Lemieux, Jacob E.

doi:10.1101/2022.03.02.22271731

Cited by 21 publications

(40 citation statements)

References 30 publications

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“…This is in line with other studies where an omicron variant re-infection not only increased neutralizing antibody titers against omicron but also against other variants. 26,27 Surprisingly, we found that a delta variant breakthrough infection induced high titers against both omicron sub-lineages, although these individuals were never exposed to the omicron variant. In these individuals, neutralizing antibody titers against both omicron sub-variants were comparable to individuals who had a combination of prior infection/vaccination and omicron infection.…”

Section: Discussionmentioning

confidence: 71%

“…However, others also found improved levels and durability of cross-neutralizing antibodies after three or more exposures (vaccination or infection). 3,8,27 In a non-human primate model, titers of cross-neutralizing antibodies were similarly increased by either a third dose of a wild type-specific mRNA vaccine or a beta-specific mRNA vaccine after two doses of a wild type-specific mRNA vaccine. 28…”

Section: Discussionmentioning

confidence: 98%

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BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Rössler

Netzl

Knabl³

et al. 2022

Preprint

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BackgroundSeveral studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.MethodsWe characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naïve, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes.ResultsUnvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.ConclusionsHere, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 98%

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Rössler

Netzl

Knabl³

et al. 2022

Preprint

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“…Understanding the role of antigenic imprinting in shaping the B cell response to antigenically drifted SARS-CoV-2 variants will be critical for the development of next-generation COVID-19 vaccines. Previous studies have shown that breakthrough infection with Delta or Omicron boosts serum neutralizing activity against both the Wuhan-1 vaccine strain and the infecting variant, suggesting recall of cross-reactive vaccine-induced MBCs ( 12–14 ). However, the specificities, functions, and genetic features of the antibodies mediating this response remain poorly defined.…”

Section: Main Textmentioning

confidence: 99%

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Kaku

Bergeron

Ahlm

et al. 2022

Preprint

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Understanding immune responses following SARS-CoV-2 breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit toward the receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 variants of concern (VOCs). Together, these findings provide fundamental insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

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“…Understanding the role of antigenic imprinting in shaping the B cell response to antigenically drifted SARS-CoV-2 variants will be critical for the development of next-generation COVID-19 vaccines. Previous studies have shown that Delta or Omicron breakthrough infection boosts serum neutralizing activity against both the Wuhan-1 vaccine strain and the infecting variant, potentially suggesting recall of cross-reactive vaccine-induced MBCs ( 12 – 14 ). However, the specificities, functions, and genetic features of the antibodies mediating this response remain poorly defined.…”

Section: Introductionmentioning

confidence: 99%

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

et al. 2022

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Understanding immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

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Vaccine Breakthrough Infection with the SARS-CoV-2 Delta or Omicron (BA.1) Variant Leads to Distinct Profiles of Neutralizing Antibody Responses

Cited by 21 publications

References 30 publications

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

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