The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

Koutsakos, Marios; Lee, Wen Shi; Reynaldi, Arnold; Tan, Hyon‐Xhi; Gare, Grace; Kinsella, Paul; Liew, Kwee Chin; Taiaroa, George; Williamson, Deborah A; Kent, Helen E; Stadler, Eva; Cromer, Deborah; Khoury, David S.; Wheatley, Adam K.; Juno, Jennifer A; Davenport, Miles P.; Kent, Stephen J.

doi:10.1016/j.immuni.2022.05.018

Cited by 44 publications

(32 citation statements)

References 40 publications

(40 reference statements)

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“…In contrast to BA.4 and BA.5, we detected only minor escape of BA.2 from BA.1 elicited immunity in the same cohort of BA.1 infected individuals in a previous study 21 . As we previously reported 21 and confirmed here, BA.1 elicits relatively weak neutralization in the absence of vaccination, consistent with reports showing that Omicron has reduced immunogenicity [24][25][26] . Even with BA.1 breakthrough infection, the FRNT 50 against ancestral virus was about half of that measured in a group composed mostly (Table S1) of people with ancestral infection and vaccination hybrid immunity (Fig.…”

Section: Resultssupporting

confidence: 93%

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

et al. 2022

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SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vaccination as well as from vaccination without BA.1 infection. In BA.1-infected unvaccinated individuals, neutralization relative to BA.1 declines 7.6-fold for BA.4 and 7.5-fold for BA.5. In vaccinated individuals with subsequent BA.1 infection, neutralization relative to BA.1 decreases 3.2-fold for BA.4 and 2.6-fold for BA.5. The fold-drop versus ancestral virus neutralization in this group is 4.0-fold for BA.1, 12.9-fold for BA.4, and 10.3-fold for BA.5. In contrast, BA.4/BA.5 escape is similar to BA.1 in the absence of BA.1 elicited immunity: fold-drop relative to ancestral virus neutralization is 19.8-fold for BA.1, 19.6-fold for BA.4, and 20.9-fold for BA.5. These results show considerable escape of BA.4/BA.5 from BA.1 elicited immunity which is moderated with vaccination and may indicate that BA.4/BA.5 may have the strongest selective advantage in evading neutralization relative to BA.1 in unvaccinated, BA.1 infected individuals.

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Section: Resultssupporting

confidence: 93%

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

et al. 2022

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“…Firstly, it is still unclear why the risk of death is lower. Is this due to omicron’s increased capacity to avoid immune recall67 leading to lower immune activation, altered viral tropism,89 changes in anatomical localisation,10 improvements in clinical care, or a combination of these and other factors? Understanding the causes is critical for assessing risks as variants continue to emerge.…”

mentioning

confidence: 99%

Covid-19: is omicron less lethal than delta?

Lorenzo-Redondo

Ozer

Hultquist

2022

BMJ

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“…It is also unclear how our finding observed with BNT162b2 -vaccination will translate to other SARS-CoV-2 vaccines with more or less potent responses (such as mRNA-1273, adenoviral vectors, inactivated viruses, and protein subunit vaccines). Furthermore, neutralizing antibody responses elicited from current Omicron BA.2 infections have been shown to differ from that of earlier waves (Omicron BA.1 and Delta) and this will also likely impact the specificity of RBD responses (52). Lastly, due to resource constraints, we opted to use commercially available Omicron BA.2 and WT RBD to study responses against Omicron.…”

Section: Discussionmentioning

confidence: 99%

Altered affinity to ACE2 and reduced Fc functional antibodies to SARS-CoV-2 RBD variants

Haycroft

Davis

Ramanathan

et al. 2022

Preprint

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains a formidable challenge to worldwide public health. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. We comprehensively investigated the impact of RBD mutations, including 6 variants of concern (VOC) or interest (Alpha, Beta, Gamma, Delta, Kappa and Omicron) and 33 common point mutations, on IgG recognition, FcgR-engagement, and ACE2-binding inhibition in plasma from BNT162b2-vaccine recipients (two-weeks following second dose) and mild-to-moderate COVID-19 convalescent subjects using our custom bead-based 39-plex array. We observed that IgG-recognition and FcgR-binding antibodies were most profoundly decreased against Beta and Omicron RBDs, as well as point mutations G446S, found in Omicron, and N501T, a key mutation found in animal adapted SARS-CoV-2 viruses. Measurement of RBD-ACE2 binding affinity via Biolayer Interferometry showed all VOC RBDs have enhanced affinity to human ACE2. Furthermore we demonstrate that human ACE2 polymorphisms, E35K (rs1348114695), K26R (rs4646116) and S19P (rs73635825), have altered binding kinetics to the RBD of VOCs potentially affecting virus-host interaction and thereby host susceptibility.

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The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

Cited by 44 publications

References 40 publications

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Covid-19: is omicron less lethal than delta?

Altered affinity to ACE2 and reduced Fc functional antibodies to SARS-CoV-2 RBD variants

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