Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity

Jia, Liqiu; Weng, Shufeng; Wu, Jing; Tian, Xiangxiang; Zhang, Yifan; Wang, Xuyang; Wang, Jing; Yan, Dongmei; Wang, Wanhai; Fang, Fang; Zhu, Zhaoqin; Qiu, Chao; Zhang, Wenhong; Xu, Ying; Wan, Yanmin

doi:10.1080/19490976.2022.2117503

Cited by 11 publications

(9 citation statements)

References 63 publications

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“…Mice with pre-existing high levels of S2 cross-reactive antibodies produced higher S protein-specific binding antibodies, especially antibodies against S2, after immunization with the SARS-COV-2 S DNA vaccine. Similarly, pre-existing S2- and P144-specific antibody levels were positively correlated with receptor-binding domain-specific antibody titers after vaccinating two doses of inactivated SARS-COV-2 vaccine in humans [ 30 ]. These studies suggested that gut microbiota could affect vaccine efficacy by inducing cross-immunity by carrying vaccine-like epitopes.…”

Section: Gut Microbiota Affects Vaccine Efficacy By Modulating the Im...mentioning

confidence: 99%

Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms

Huang¹,

Wang²,

Li³

2023

Gut Pathog

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Vaccine is the most effective way to prevent the spread of communicable diseases, but the immune response induced by it varies greatly between individuals and populations in different regions of the world. Current studies have identified the composition and function of the gut microbiota as key factors in modulating the immune response to vaccination. This article mainly reviews the differences in gut microbiota among different groups of vaccinated people and animals, explores the possible mechanism of vaccine immunity affected by gut microbiota, and reviews the strategies for targeting gut microbiota to improve vaccine efficacy.

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Section: Gut Microbiota Affects Vaccine Efficacy By Modulating the Im...mentioning

confidence: 99%

Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms

Huang¹,

Wang²,

Li³

2023

Gut Pathog

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“…Alternatively, cross-reactivity to past microorganism exposures not addressed in this study could be at play. For instance, the SARS-CoV-2 S protein S2 subunit (S686-1273) has been reported to harbour cross-reactive epitopes elicited by commensal microorganisms [103]. Finally, homology clustering can only suggest cross-reactivity between the different HCoV HFRs.…”

Section: Discussionmentioning

confidence: 99%

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Bach,

Ghanizada,

Kirkby

et al. 2024

Preprint

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Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.

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“…Our data also elucidated that the anti-vaccinia neutralizing antibody responses were not associated with prior STIs, which dismissed the possibility that the higher levels of neutralizing antibody responses among the gay men aged ≤ 41 were induced by STIs. A potential explanation for this phenomenon is that the pre-existing anti-MPXV antibodies might be cross-reactive antibodies induced by commensal microbial antigens or other human pathogens, which has been suggested by studies of anti-HIV [ 46 – 48 ], anti-SARS-CoV-2 [ 49 , 50 ] and anti-influenza cross-reactive antibodies [ 51 ]. Although high levels of neutralizing antibodies against vaccinia virus could potentially provide protection against MPXV, the fact that individuals can acquire monkeypox despite smallpox vaccination [ 52 ] highlights the highly efficient transmission of MPXV through intimate contact might not be easily blocked by the pre-existing cross-reactive antibodies in real world.…”

Section: Discussionmentioning

confidence: 99%

Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population

Feng

Zhang

Liu

et al. 2023

BMC Med

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Background The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized. Methods A cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately. Results Our data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort. Conclusions Anti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.

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Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity

Cited by 11 publications

References 63 publications

Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms

Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population

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