SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals

Ruggiero, Alessandra; Piubelli, Chiara; Calciano, Lucia; Accordini, Simone; Valenti, Maria Teresa; Carbonare, Luca Dalle; Siracusano, Gabriel; Temperton, Nigel; Tiberti, Natalia; Longoni, Silvia Stefánia; Pizzato, Massimo; Accordini, Silvia; Fantoni, Tobia; Lopalco, Lucia; Beretta, Alberto; Bisoffi, Zeno; Zipeto, Donato

doi:10.1016/j.ebiom.2022.103888

Cited by 52 publications

(60 citation statements)

References 36 publications

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“…Additionally, IgM response peaked after the second vaccine dose, and we observed strong correlations between IgM and IgG responses after the first and second doses (Fig. 2A and S8A), indicating the simultaneous production of IgM and IgG, as reported previously ( 36 ), irrespective of age. Although the antibody levels were highly variable among individuals, even within the same age cohort, we observed a negative correlation between age and peak IgG titers after the second dose (r = −0.39; p < 0.001) (Fig.…”

Section: Resultssupporting

confidence: 87%

Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Hidaka

Kikuchi

et al. 2022

Preprint

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Despite the clinical efficacy of coronavirus disease 2019 mRNA vaccines, the elderly demonstrate lower IgG levels and neutralizing titers and a higher risk of severe diseases. CD4+ T cells play a central role in regulating antigen-specific antibody and CD8+ T-cell responses; however, because their composition and functionality change significantly with age, relationships between age-associated defects in T cells and the immunogenicity of or reactogenicity to mRNA vaccines are unclear. Using a vaccine cohort (n = 216), we found that the elderly (aged ≥65 years) showed delayed induction and early contraction of vaccine-specific CD4+ T cells, and that the compromised C–X–C motif chemokine receptor 3+ circulating T follicular helper cell response after the first dose was associated with the lower IgG levels. Additionally, the elderly experienced significantly fewer systemic adverse effects (AEs) after the second dose, with those exhibiting few AEs showing lower cytokine+ CD4+ T cells after the first dose and lower antibody levels after the second dose. Furthermore, T helper 1 cells in the elderly expressed higher levels of programmed cell death protein-1, a negative regulator of the T-cell response, which was associated with less production of vaccine-specific CD4+ T cells and impaired CD8+ T-cell expansion. Thus, efficient induction of vaccine-specific effector/memory CD4+ T cells after the first dose may trigger robust cytokine production after the second dose, leading to effective vaccine responses and higher systemic reactogenicity. These results suggested that an enhanced CD4+ T-cell response after the first dose is key to improved vaccination efficacy in the elderly.One Sentence SummaryWe compared immunogenicity and reactogenicity to COVID-19 mRNA vaccine in 107 adults (aged <65 years) and 109 elderly (aged ≥65) individuals.

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Section: Resultssupporting

confidence: 87%

Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Hidaka

Kikuchi

et al. 2022

Preprint

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“…Extended studies that focus on the antibody levels triggered by infection and/or by vaccination have reported the existance of an entire panel of specific immunoglobulines 5 . Moreover, recent studies show that cross immunity against coronaviruses can be elicited by vaccination 6 but still we have to focus on the relevance of the booster vaccination. Within the total population, healthcare workers (HCW) represent the highly exposed populational segment to virus threatening.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity evaluation after BNT162b2 booster vaccination in healthcare workers

Zurac

Vlădan

Dincă

et al. 2022

Sci Rep

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Waning of the immune response upon vaccination in SARS-CoV-2 infection is an important subject of evaluation in this pandemic, mostly in healthcare workers (HCW) that are constantly in contact with infected samples and patients. Therefore, our study aimed to establish the specific humoral response of specific IgG and IgA antibodies upon vaccination, during the second year of pandemic and evaluating the booster shot with the same vaccine type. A group of 103 HCW with documented exposure to the virus were monitored for specific IgG and IgA levels prior to vaccination, after the first vaccination round, during the following 8 months and after the booster shot with the same vaccine type. After 8 months post-vaccination the humoral response in both IgG and IgA decreased, 2.4 times for IgG, and 2.7 times for IgA. Although the antibodies levels significantly decreased, no documented infection was registered in the group. After the booster shot, the entire group, displayed IgG increased levels, immediately after booster followed by the increase in specific IgA. IgG levels post-second round of vaccination are statistically higher compared to the first round, while IgA is restored at the same levels. Within the vaccination or booster routine for a multiple waves’ pandemic that is generating new virus variants, populational immunity remains an important issue for future implementation of prevention/control measures.

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“…Examination of anti-RBD IgM revealed no significant differences between any of the groups tested, which is probably due to the time point at which samples were collected. Anti-RBD IgM levels are significantly decreased at 6 months post infection[18], in addition, vaccination does not elicit formation of anti-RBD IgM as natural infection [19], both reasons account for our finding of no significant difference in anti-RBD IgM levels. This study also indicated that anti-RBD IgG but not IgM was more important in complement activation following vaccination, where C5b-9 strongly and significantly correlated to the amount of bound C1q, which in turn strongly correlated to the amount of bound anti-RBD-IgG but not IgM.…”

Section: Discussionmentioning

confidence: 97%

Anti-SARS-Cov-2 S-RBD IgG formed after BNT162b2 vaccination can bind C1q and activate complement

Abu-Humaidan

Ahmad

Awajan

et al. 2022

Preprint

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IntroductionActivation of the classical complement pathway through C1q binding to immunoglobulins (Ig) contributes to pathogen neutralization, thus, the ability of Ig produced after vaccination to bind C1q could affect vaccine efficacy. In this study, we investigated C1q binding and subsequent complement activation by anti-spike (S) protein receptor-binding domain (RBD) specific antibodies produced following vaccination with either the mRNA vaccine BNT162b2 or the inactivated vaccine BBIBP-CorV.MethodsSerum samples were collected in the period July 2021-March 2022. Participants’ demographic data, type of vaccine, date of vaccination, as well as adverse effects of the vaccine were recorded. The serum samples were incubated with S protein RBD-coated plates. Levels of human IgG, IgM, and C1q, that were bound to the plate, as well as formed C5b-9, were compared between different groups of participants.ResultsA total of 151 samples were collected from vaccinated (n=116) and non-vaccinated (n=35) participants. Participants who received either one or two doses of BNT162b2 formed higher levels of anti-RBD IgG than participants who received BBIBP-CorV. The anti-RBD IgG formed following either vaccine bound C1q, but significantly more C1q binding was observed in participants who received BNT162b2. Subsequently, C5b-9 formation was significantly higher in participants who received BNT162b2, while no significant difference in C5b-9 formation was found between the non-vaccinated and BBIBP-CorV groups. Formation of C5b-9 was strongly correlated to C1q binding, additionally, the ratio of formed C5b-9/ bound C1q was significantly higher in the BNT162b2 group.ConclusionAnti-RBD IgG formed following vaccination can bind C1q with subsequent complement activation, the degree of terminal complement pathway activation differed between vaccines, which could play a role in in the protection offered by COVID-19 vaccines. Further investigation into the correlation between vaccine protection and the ability of vaccine generated antibodies to activate complement is required.

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SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals

Cited by 52 publications

References 36 publications

Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Immunogenicity evaluation after BNT162b2 booster vaccination in healthcare workers

Anti-SARS-Cov-2 S-RBD IgG formed after BNT162b2 vaccination can bind C1q and activate complement

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SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals

Cited by 52 publications

References 36 publications

Delayed antigen-specific CD4+ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Delayed antigen-specific CD4+ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Immunogenicity evaluation after BNT162b2 booster vaccination in healthcare workers

Anti-SARS-Cov-2 S-RBD IgG formed after BNT162b2 vaccination can bind C1q and activate complement

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Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly

Delayed antigen-specific CD4⁺ T-cell induction correlates with impaired immune responses to SARS-COV-2 mRNA vaccination in the elderly