Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection

Gunn, Bronwyn M.; Bai, Shuangyi

doi:10.1080/21645515.2021.1976580

Cited by 18 publications

(17 citation statements)

References 209 publications

(279 reference statements)

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“…We did not analyse neutralising antibodies, which are considered to be the best humoral correlate of protection, but instead analysed antibodies binding the S1 or S2 domains of SARS-CoV-2 spike, including the receptor binding domain. Importantly, non-neutralising antibodies may be the first line of antigen-specific defence, mediating phagocytosis [ 35 ] and serving as surrogate markers of the T-cell response [ 36 ]. Moreover, a strong correlation has been observed between anti-S IgG titres and neutralising antibody titers [ 22 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamics of SARS-CoV-2 Spike-IgG throughout Three COVID-19 Vaccination Regimens: A 21-Month Longitudinal Study of 82 Norwegian Healthcare Workers

Augustinussen

Tylden

Rinaldo

2023

Viruses

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To facilitate interpretation of clinical SARS-CoV-2 anti-spike IgG analyses post-vaccination, 82 healthcare workers were followed through three vaccination-regimens: two regimens were comprised of two doses of BNT162b2 three or six weeks apart, followed by a dose of mRNA-vaccine, and in the other regimen, the first dose was replaced by ChAdOx1 nCov-19. After each dose, anti-spike IgG was compared between regimens. As many participants became infected, anti-spike IgG persistence was compared between infected and uninfected participants. Thirteen to twenty-one days after the first dose, seroconversion, and the median anti-spike IgG level in the ChAdOx1 group was significantly lower than in the BNT162b2 groups (23 versus 68 and 73 AU/mL). The second dose caused a significant increase in anti-spike IgG, but the median level was lower in the BNT162b2-short-interval group (280 AU/mL), compared to the BNT162b2-long-interval (1075 AU/mL) and ChAdOx1 (1160 AU/mL) group. After the third dose, all groups showed increases to similar anti-spike IgG levels (2075–2390 AU/mL). Over the next half year, anti-spike IgG levels declined significantly in all groups, but appeared to persist longer after post-vaccination infection. This is the first three-dose study with one dose of ChAdOx1. Despite initial differences, all vaccine regimens gave similarly high antibody levels and persistence after the third dose.

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Section: Discussionmentioning

confidence: 99%

Dynamics of SARS-CoV-2 Spike-IgG throughout Three COVID-19 Vaccination Regimens: A 21-Month Longitudinal Study of 82 Norwegian Healthcare Workers

Augustinussen

Tylden

Rinaldo

2023

Viruses

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“…We believe that the neutralizing ability of antibodies formed against SARS-COV-2 should be investigated in the presence and absence of C1q and other complement components, especially in light of advancements that allow the manipulation of the Fc portion of monoclonal antibodies to enhance effector functions [23], a process that is relevant in vaccine production as well [24].…”

Section: Discussionmentioning

confidence: 99%

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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“…We believe that the neutralizing ability of antibodies formed against SARS-COV-2 should be investigated in the presence and absence of C1q, MBL, and other complement components, especially in light of advancements that allow the manipulation of the Fc portion of monoclonal antibodies to enhance effector functions [ 33 ], a process that is relevant in vaccine production as well [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-SARS-Cov-2 S-RBD IgG Formed after BNT162b2 Vaccination Can Bind C1q and Activate Complement

Abu-Humaidan

Ahmad

Awajan

et al. 2022

Journal of Immunology Research

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Background. The ability of vaccine-induced antibodies to bind C1q could affect pathogen neutralization. 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. Methods. Serum samples were collected in the period of 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, IgA, IgM, C1q, and mannose-binding lectin (MBL) that were bound to the plate, as well as formed C3d, and C5b-9 were compared between different groups of participants. Results. A total of 151 samples were collected from vaccinated ( n = 116 ) and nonvaccinated ( n = 35 ) participants. Participants who received either one or two doses of BNT162b2 formed higher levels of anti-RBD IgG and IgA 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 nonvaccinated and BBIBP-CorV groups. The formation of C5b-9 was strongly correlated to C1q binding and not to MBL binding, additionally, the ratio of formed C5b-9/bound C1q was significantly higher in the BNT162b2 group. Conclusion. Anti-RBD IgG formed following vaccination can bind C1q with subsequent complement activation, and the degree of terminal complement pathway activation differed between vaccines, which could play a role in the protection offered by COVID-19 vaccines. Further investigation into the correlation between vaccine protection and vaccine-induced antibodies’ ability to activate complement is required.

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Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection

Cited by 18 publications

References 209 publications

Dynamics of SARS-CoV-2 Spike-IgG throughout Three COVID-19 Vaccination Regimens: A 21-Month Longitudinal Study of 82 Norwegian Healthcare Workers

Dynamics of SARS-CoV-2 Spike-IgG throughout Three COVID-19 Vaccination Regimens: A 21-Month Longitudinal Study of 82 Norwegian Healthcare Workers

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

Anti-SARS-Cov-2 S-RBD IgG Formed after BNT162b2 Vaccination Can Bind C1q and Activate Complement

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