Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Zanella, Isabella; Antoni, Melania Degli; Marchese, Valentina; Castelli, Francesco; Quirós-Roldán, Eugenia

doi:10.1016/j.intimp.2022.108943

Cited by 8 publications

(6 citation statements)

References 66 publications

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“…One plausible hypothesis is that the majority of these elderly patients, who endured severe manifestations of COVID-19 requiring hospitalization but successfully overcame the infection, might have developed an adaptive anti-SARS-CoV-2 response, leading to the preferential development of neutralizing antibodies. Furthermore, the absence of facilitating Abs in elderly patients with severe forms of the disease is consistent with existing literature, which establishes no correlation between disease severity and the presence of enhancing Abs [ 22 ].…”

Section: Discussionsupporting

confidence: 87%

Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants

Coutant,

Touret,

et al. 2024

Emerging Microbes & Infections

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Serological studies of COVID-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies (Abs), with varying effector functions against virus variants. Individual specificities of anti-SARS-CoV-2 Abs and their impact on infectivity by other variants have been little investigated to date. Here, we dissected at a monoclonal level neutralizing and enhancing Abs elicited by early variants and how they affect infectivity of emerging variants. B cells from 13 convalescent patients originally infected by D614G or Alpha variants were immortalized to isolate 445 naturally-produced anti-SARS-CoV-2 Abs. Monoclonal antibodies (mAbs) were tested for their abilities to impact the cytopathic effect of D614G, Delta, and Omicron (BA.1) variants. Ninety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. Thirty-eight mAbs enhanced infectivity of SARS-CoV-2. Infection with D614G/Alpha variants generated variant-specific (65 neutralizing Abs, 35 enhancing Abs) and cross-reactive (18 neutralizing Abs, 3 enhancing Abs) mAbs. Interestingly, among the neutralizing mAbs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the Delta and Omicron variants. In contrast, cross-reactive mAbs enhancing infectivity ( n = 3) were found exclusively specific to Delta and Omicron variants. Notably, two mAbs that amplified in vitro the cytopathic effect of the Delta variant also exhibited neutralization against Omicron. These findings shed light on functional diversity of cross-reactive Abs generated during SARS-CoV-2 infection and illustrate how the balance between neutralizing and enhancing Abs facilitate variant emergence.

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Section: Discussionsupporting

confidence: 87%

Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants

Coutant,

Touret,

et al. 2024

Emerging Microbes & Infections

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“…How does a virus use antibodies to enter an immune cell? The process resembles the piggybacking approach, in which “piggyback” is an IgG antibody and the entry gates to a pig barn are Fcγ receptors (FcγRs) of immune phagocytic cells ( 131 , 132 ). It is thought that myeloid cells expressing FcγRs, such as monocytes and macrophages, dendritic cells, and some granulocytes, can become ADE targets through phagocytic uptake of immune complexes ( 128 ).…”

Section: Mainmentioning

confidence: 99%

SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry

et al. 2022

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Our review summarizes the evidence that COVID-19 can be complicated by SARS-CoV-2 infection of immune cells. This evidence is widespread and accumulating at an increasing rate. Research teams from around the world, studying primary and established cell cultures, animal models, and analyzing autopsy material from COVID-19 deceased patients, are seeing the same thing, namely that some immune cells are infected or capable of being infected with the virus. Human cells most vulnerable to infection include both professional phagocytes, such as monocytes, macrophages, and dendritic cells, as well as nonprofessional phagocytes, such as B-cells. Convincing evidence has accumulated to suggest that the virus can infect monocytes and macrophages, while data on infection of dendritic cells and B-cells are still scarce. Viral infection of immune cells can occur directly through cell receptors, but it can also be mediated or enhanced by antibodies through the Fc gamma receptors of phagocytic cells. Antibody-dependent enhancement (ADE) most likely occurs during the primary encounter with the pathogen through the first COVID-19 infection rather than during the second encounter, which is characteristic of ADE caused by other viruses. Highly fucosylated antibodies of vaccinees seems to be incapable of causing ADE, whereas afucosylated antibodies of persons with acute primary infection or convalescents are capable. SARS-CoV-2 entry into immune cells can lead to an abortive infection followed by host cell pyroptosis, and a massive inflammatory cascade. This scenario has the most experimental evidence. Other scenarios are also possible, for which the evidence base is not yet as extensive, namely productive infection of immune cells or trans-infection of other non-immune permissive cells. The chance of a latent infection cannot be ruled out either.

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“…The fraction that mainly decreases may correspond to non-neutralizing antibodies, which carry out effector functions, such as ADCP, ADCC, and CDC, all of which are essential mechanisms for eliminating infected cells [ 28 , 37 ]. However, the persistence of these antibodies before primary infection or reinfection, could develop an antibody-dependent enhancement (ADE) in the individual, a phenomenon that increases the virulence of antibody-mediated pathogens [ 38 ]. Therefore, the rapid decrease in these antibodies could be a protective mechanism against ADE.…”

Section: Discussionmentioning

confidence: 99%

BNT162b2 Vaccination after SARS-CoV-2 Infection Changes the Dynamics of Total and Neutralizing Antibodies against SARS-CoV-2: A 6-Month Prospective Cohort Study

Hernández-Bello,

Sierra-García-de-Quevedo,

Morales-Núñez

et al. 2023

Vaccines

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This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated individuals without prior SARS-CoV-2 infection, with an exponential increase observed in just six days. In those without a COVID-19 history, similar antibody production was reached 45 days after vaccination. Although total antibodies decline considerably in the first two months, the neutralizing antibodies and their inhibitory capacity (>96%) persist up to 6 months after the first dose. There was a tendency for higher total antibodies in women than men, but not at the inhibition capacity level. We suggest that the decline in total antibodies should not be considered as an indicator of loss of protective immunity because most antibodies decay two months after the second dose, but neutralizing antibodies remain constant for at least six months. Therefore, these latter antibodies could be better indicators for estimating the time-dependent vaccine efficacy.

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Non-neutralizing antibodies: Deleterious or propitious during SARS-CoV-2 infection?

Cited by 8 publications

References 66 publications

Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants

Neutralizing and enhancing monoclonal antibodies in SARS-CoV-2 convalescent patients: lessons from early variant infection and impact on shaping emerging variants

SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry

BNT162b2 Vaccination after SARS-CoV-2 Infection Changes the Dynamics of Total and Neutralizing Antibodies against SARS-CoV-2: A 6-Month Prospective Cohort Study

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