Protective effect of plasma neutralization from prior SARS-CoV-2 Omicron infection against BA.5 subvariant symptomatic reinfection

Chen, Xiaosu; Xie, Yan; Song, Weiliang; Hu, Ye; Yisimayi, Ayijiang; Yang, Sijie; Shao, Fei; Geng, Lanlan; Wang, Ying; Gao, Hongmei; Shi, Yansong; Zhang, Shuo; Jin, Ronghua; Shen, Zhongyang; Cao, Yunlong

doi:10.1016/j.lanwpc.2023.100758

Cited by 12 publications

(6 citation statements)

References 6 publications

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“…In addition to weaker IgG responses, asymptomatic participants also exhibited fewer Wuhan-speci c neutralization antibodies pre-and post-vaccination, as well as fewer Omicron-speci c neutralization antibodies post-vaccination, which is also demonstrated in previous research (15,(31)(32)(33). There is a protective effect of neutralization antibodies against future re-infection (34), suggesting symptomatic individuals could be better protected against SARS-CoV-2 re-infection compared to asymptomatic individuals. As expected, both Wuhan and Omicron neutralising antibodies positively correlated to total anti-spike antibody titre.…”

Section: Discussionsupporting

confidence: 75%

Lower Humoral and Cellular Immunity following Asymptomatic SARS-CoV-2 Infection in Education (The ACE Cohort)

Hopkins,

Gomez,

Tucis

et al. 2024

Preprint

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Purpose Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort). Methods Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. Anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron variants. Results Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis of indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination. Conclusions Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.

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Section: Discussionsupporting

confidence: 75%

Lower Humoral and Cellular Immunity following Asymptomatic SARS-CoV-2 Infection in Education (The ACE Cohort)

Hopkins,

Gomez,

Tucis

et al. 2024

Preprint

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“…To verify whether the findings obtained from mice also apply to humans, we recruited cohorts with repeated Omicron breakthrough infections (BTIs), including individuals with post-vaccination either BA.1 or BA.2 BTI followed by BA.5/BF.7 (the specific variant was not determined) reinfection (BTI + reinfection) and compared them to previously reported BA.1, BA.2, BA.5, BF.7 one-time BTI cohorts 3 , 32 , 37 , 38 . Of note, we also included individuals who had no history of SARS-CoV-2 vaccination before repeated infection (vaccination-naive reinfection) as controls (Supplementary Table 1 ).…”

Section: Mitigating Immune Imprinting In Humansmentioning

confidence: 99%

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Yisimayi,

Song,

Wang

et al. 2023

Nature

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107

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The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1–5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT—such as the XBB variant—and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.

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“…To verify whether findings obtained from mice can also be applied to humans, we recruited cohorts with repeated Omicron breakthrough infections (BTIs), including individuals with post-vaccination BA.1 or BA.2 BTI followed by BA.5/BF.7 reinfection (BTI+reinfection) and compared them to previously reported BA.1, BA.2, BA.5, BF.7 one-time BTI cohorts 7, 29 . Importantly, we also included individuals who had no history of SARS-CoV-2 vaccination before repeated infection (vaccinationnaïve reinfection) as controls.…”

Section: Mitigating Immune Imprinting In Humansmentioning

confidence: 99%

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Yisimayi

Song

Wang

et al. 2023

Preprint

Self Cite

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The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5's immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven't been exposed to Omicron yet should receive two updated vaccine boosters.

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Protective effect of plasma neutralization from prior SARS-CoV-2 Omicron infection against BA.5 subvariant symptomatic reinfection

Cited by 12 publications

References 6 publications

Lower Humoral and Cellular Immunity following Asymptomatic SARS-CoV-2 Infection in Education (The ACE Cohort)

Lower Humoral and Cellular Immunity following Asymptomatic SARS-CoV-2 Infection in Education (The ACE Cohort)

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

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