A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain

Wang, Ji; Deng, Caiguangxi; Liu, Ming; Liu, Yihao; Li, Liubing; Huang, Zhangping; Shang, Liru; José, Juán; Li, Yongyong; Mo, Ruohui; Zhang, Hui; Liu, Min; Peng, Sui; Xiao, Haipeng

doi:10.1038/s41467-022-34633-7

Cited by 23 publications

(42 citation statements)

References 35 publications

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“…By studying the antigenspecificity of the Spike response, we identified Spike/NTD as a specific IgA target that correlated with seroneutralization titers. A shift of the humoral response toward the Spike/NTD domain had previously been described after the second boost, despite the fact that some Omicron sublineages displayed several NTD mutations (38). Monoclonal antibodies targeting the Spike/NTD have shown in previous studies their ability to inhibit cell-to-cell fusion, to activate effector functions and to protect Syrian hamsters from SARS-CoV-2 challenge (39).…”

Section: Discussionmentioning

confidence: 90%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Front. Immunol.

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IntroductionCurrent approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission.MethodsWe measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer).ResultsWhile serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19.DiscussionAs breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

show abstract

Section: Discussionmentioning

confidence: 90%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…By studying the antigenspecificity of the Spike response, we identified Spike/NTD as a specific IgA target that correlated with seroneutralization titers. A shift of the humoral response toward the Spike/NTD domain had previously been described after the second boost, despite the fact that some Omicron sublineages displayed several NTD mutations (37). Monoclonal antibodies targeting the Spike/NTD have shown in previous studies their ability to inhibit cell-to-cell fusion, to activate effector functions and to protect Syrian hamsters from SARS-CoV-2 challenge (38).…”

Section: Discussionmentioning

confidence: 90%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Preprint

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Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria/Astrazeneca and/or Comirnaty/Pfizer). While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19, and could potentially be used as an early prognosis biomarker.

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“…Wang et al demonstrated that non-spike and spike T cell responses as assayed by ELISPOT were readily detectable 6 months after the third dose of inactivated vaccine BBIBP-CorV (Covilo). A homologous booster 6 months after the third dose failed to further enhance T cell responses (39). Melo-Gonzaĺez et al reported that AIM + CD4 + T cell response remained stable after the third dose of CoronaVac, but showed a decline 4-6 months later (40).…”

Section: Discussionmentioning

confidence: 99%

“…demonstrated that non-spike and spike T cell responses as assayed by ELISPOT were readily detectable 6 months after the third dose of inactivated vaccine BBIBP-CorV (Covilo). A homologous booster 6 months after the third dose failed to further enhance T cell responses ( 39 ). Melo-González et al.…”

Section: Discussionmentioning

confidence: 99%

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine

et al. 2023

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BackgroundDuring the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited.MethodsIn this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4+ and CD8+ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose. ResultsThe booster dose elevated cytokine response in CD4+ and CD8+ T cells as well as expression of cytotoxic marker CD107a in CD8+ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4+ and CD8+ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4+ and CD8+ T cell responses. In addition, booster vaccination produced similar spike-specific AIM+CD4+ and AIM+CD8+ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4+ and CD8+ T cells. ConclusionsThese data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.

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A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain

Cited by 23 publications

References 35 publications

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine

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