Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants

Qu, Panke; Faraone, Julia N.; Evans, John P.; Zheng, Yi-Min; Carlin, Claire; Anghelina, Mirela; Stevens, Patrick; Fernández, Soledad; Jones, Daniel M.; Panchal, Ashish R.; Saif, Linda J.; Oltz, Eugene M.; Zhang, Baoshan; Zhou, Tongqing; Xu, Kai; Gumina, Richard J.; Liu, Shan-Lu

doi:10.1016/j.celrep.2023.112443

Cited by 117 publications

(64 citation statements)

References 46 publications

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“…We and others have previously reported that the acute B cell response following Omicron BA.1 breakthrough infection is dominated by re-activated memory B cells induced by mRNA vaccination 12 – 15 . Consistent with these findings, booster immunization with Omicron variant-containing mRNA vaccines induces modestly higher (up to fivefold) peak serum-neutralizing antibody responses compared with booster vaccination with the original mRNA vaccines based on the Wuhan-1 strain 8 , 9 , 11 , 16 , 17 . Although these studies provide evidence for antigenic imprinting in the early B cell response following Omicron breakthrough infection, if and how this response evolves over time remains unclear.…”

Section: Introductionsupporting

confidence: 64%

Evolution of antibody immunity following Omicron BA.1 breakthrough infection

et al. 2023

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Understanding the longitudinal dynamics of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we track SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in six mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses decline by two- to four-fold through the study period. Breakthrough infection elicits minimal de novo Omicron BA.1-specific B cell responses but drives affinity maturation of pre-existing cross-reactive MBCs toward BA.1, which translates into enhanced breadth of activity across other variants. Public clones dominate the neutralizing antibody response at both early and late time points following breakthough infection, and their escape mutation profiles predict newly emergent Omicron sublineages, suggesting that convergent antibody responses continue to shape SARS-CoV-2 evolution. While the study is limited by our relatively small cohort size, these results suggest that heterologous SARS-CoV-2 variant exposure drives the evolution of B cell memory, supporting the continued development of next-generation variant-based vaccines.

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Section: Introductionsupporting

confidence: 64%

Evolution of antibody immunity following Omicron BA.1 breakthrough infection

et al. 2023

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“…As of 5 September 2023, there have been 41 reported sequences of BA.2.86 from 12 countries in the GISAID database, which is likely underestimated due to limited sampling. Additionally, two other circulating non-XBB Omicron subvariants CH.1.1 (a descendant of BA.2.75 sublineage) and XBC.1.6 (a recombination of Delta and Omicron sublineage BA.2) have also drawn attention due to their great immune evasion capabilities 13,16,17 . As of 29 August 2023, CH.1.1 has expanded from Southeast Asia to over 86 countries, while XBC.1.6 subvariant has steadily increased in prevalence in the Philippines and Australia (https://outbreak.info/situation-reports).…”

mentioning

confidence: 99%

Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1

Hu,

Zou,

Kurhade

et al. 2023

Preprint

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The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In comparison to XBB.1.5, the more recent XBB descendants, particularly EG.5.1 and FL.1.5.1, display increased resistance to neutralization induced by parental COVID-19 mRNA vaccine and a BA.5-Bivalent-booster. In contrast, XBC.1.6 shows a slight reduction but remains comparable sensitivity to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.

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“…In the endosomal entry pathway, Spike utilizes the cysteine protease Cathepsin L to activate and drive S2 fusion across the endosomal membrane 25,32 which does not require prior S1/S2 Spike cleavage by Furin. Whilst replication of Omicron BA.1 supports this hypothesis, post-BA.1, there has been an emergence of subsequent lineages with a continuum of S1/S2 cleavage 44,45 . To date, this has not correlated with an entry phenotype consistent with that observed for pre-Omicron lineages such as Delta.…”

Section: Discussionmentioning

confidence: 93%

“…In the endosomal entry pathway, Spike utilises the cysteine protease Cathepsin L to activated and drive S2 fusion across the endosomal membrane 24,40 and this does not require prior S1/S2 Spike cleavage by Furin. Whilst observations of Omicron BA.1 do support this hypothesis, the emergence of a number of Omicron lineages post BA.1 have observed a continuum of S1/S2 cleavage 42,43 but to date an entry phenotype not consistent with that observed for pre-Omicron lineages such as Delta. For many in vitro studies, we readily support and independently confirm that Omicron lineages may indeed be forced into using the endosomal pathway in setting where TMPRSS2 spike activation is attenuated/switched off.…”

Section: Discussionmentioning

confidence: 96%

TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by Collectrin-like domain of ACE2

Aggarwal,

Fichter,

Milogiannakis

et al. 2023

Preprint

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Continued high levels spread of SARS-CoV-2 globally enabled accumulation of changes within the Spike glycoprotein, leading to resistance to neutralising antibodies and concomitant changes to entry requirements that increased viral transmission fitness. Herein, we demonstrate a significant change in ACE2 and TMPRSS2 use by primary SARS-CoV-2 isolates that occurred upon arrival of Omicron lineages. Mechanistically we show this shift to be a function of two distinct ACE2 pools based on cleavage or non-cleavage of ACE2 by TMPRSS2 activity. In engineered cells overexpressing ACE2 and TMPRSS2, ACE2 was cleaved by TMPRSS2 and this led to either augmentation or progressive attenuation of pre-Omicron and Omicron lineages, respectfully. In contrast, TMPRSS2 resistant ACE2 restored infectivity across all Omicron lineages through enabling ACE2 binding that facilitated TMPRSS2 spike activation. Therefore, our data support the tropism shift of Omicron lineages to be a function of evolution towards the use of uncleaved pools of ACE2 with the latter consistent with its role as a chaperone for many tissue specific amino acid transport proteins.

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Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants

Cited by 117 publications

References 46 publications

Evolution of antibody immunity following Omicron BA.1 breakthrough infection

Evolution of antibody immunity following Omicron BA.1 breakthrough infection

Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1

TMPRSS2 activation of Omicron lineage Spike glycoprotein is regulated by Collectrin-like domain of ACE2

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