Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Servellita, Venice; Syed, Abdullah Muhammad; Morris, Mary Kate; Brazer, Noah; Saldhi, Prachi; Garcia-Knight, Miguel; Sreekumar, Bharath; Khalid, Mir M.; Ciling, Alison; Chen, Peiyi; Kumar, G. Renuka; Gliwa, Amelia; Nguyen, Jenny; Sotomayor-González, Alicia; Zhang, Yueyuan; Frias, Edwin C.; Prostko, John; Hackett, John; Andino, Raul; Wadford, Debra A.; Hanson, Carl V.; Doudna, Jennifer A.; Ott, Mélanie; Chiu, Charles Y.

doi:10.1016/j.cell.2022.03.019

Cited by 143 publications

(110 citation statements)

References 31 publications

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“…Booster immunization of mRNA-1273-primed individuals with a Beta spike vaccine (mRNA-1273.351) did not induce broader neutralizing antibody responses relative to homologous WT boost ( 35 ). Similarly, heterologous Delta infection in mRNA-vaccinated individuals boosted neutralizing titers to Delta but not BA.1 ( 14 ). In contrast, COVID-19 vaccination induced broadly neutralizing antibody responses to SARS-CoV-2 VOCs and highly divergent sarbecoviruses in SARS-CoV convalescent individuals, which is likely due to recall of pre-existing cross-reactive B cells induced by an antigenically divergent SARS virus ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Neutralization capacity elicited to BA.1 infection in unvaccinated participants was low, accounting for the BA.4 and BA.5 fold-drops leading to very low residual neutralization levels. The low immunity to BA.1 is perhaps reflective of lower immunogenicity of this variant 3,5 . The vaccinated group showed about 5-fold higher neutralization capacity of BA.4 and BA.5 and should be better protected, although levels may decrease with waning.…”

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confidence: 99%

Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity

Khan

Karim

Ganga

et al. 2022

Preprint

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The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both1,2. Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V mutations in the spike receptor binding domain. We isolated live BA.4 and BA.5 viruses and tested them against neutralizing immunity elicited to BA.1 infection in participants who were Omicron/BA.1 infected but unvaccinated (n=24) and participants vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV.2S with breakthrough Omicron/BA.1 infection (n=15). In unvaccinated individuals, FRNT50, the inverse of the dilution for 50% neutralization, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity1,3. However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection4.This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.

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“…Nonetheless, vaccinated subjects infected with the newer Omicron variant show the highest response against all previously characterized strains of SARS-CoV-2, which is in accordance with previously published data [ 19 ]. However, Omicron can escape NT-Abs, causing milder symptoms, which can be attributed to its reduced fitness in the lower airways [ 20 ] and reduced replication in comparison to the other variants. Moreover, as stated by other authors, the antigenic profile of the Omicron receptor binding domain (RBD) is different from previous VOC, giving a reduced antigenicity in its new receptor binding sites (RBS) [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Neutralizing Antibodies Response against 14 SARS-CoV-2 Variants in BNT162b2 Vaccinated Naïve and COVID-19 Positive Healthcare Workers from a Northern Italian Hospital

et al. 2022

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SARS-CoV-2 still represents a global health burden, causing more than six million deaths worldwide. Moreover, the emergence of new variants has posed new issues in terms of vaccine efficacy and immunogenicity. In this study, we aimed to evaluate the neutralizing antibody response against SARS-CoV-2 variants in different cohorts of vaccinated and unvaccinated subjects. Four-fold diluted sera from SARS-CoV-2 naïve and recovered subjects vaccinated with two or three doses of the BNT162b2 vaccine were challenged against 14 SARS-CoV-2 variants, and the SARS-CoV-2 neutralizing antibody titer was measured. Results were compared with those obtained from unvaccinated COVID-19 recovered patients. Overall, a better SARS-CoV-2 NT Abs response was observed in recovered vaccinated subjects after three doses of the vaccine when compared to unvaccinated patients and vaccinated subjects with only two doses. Additionally, the lowest level of response was observed against the Omicron variant. In conclusion, third doses of BNT162b2 vaccine seems to elicit a sustained response against the large majority of variants.

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Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

Cited by 143 publications

References 31 publications

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

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

Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity

Evaluation of the Neutralizing Antibodies Response against 14 SARS-CoV-2 Variants in BNT162b2 Vaccinated Naïve and COVID-19 Positive Healthcare Workers from a Northern Italian Hospital

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