@article{fdi:010089481, title = {{N}eutralizing and enhancing monoclonal antibodies in {SARS}-{C}o{V}-2 convalescent patients : lessons from early variant infection and impact on shaping emerging variants}, author = {{C}outant, {F}. and {T}ouret, {F}. and {P}in, {J}. {J}. and {A}lonzo, {M}. and {B}aronti, {C}{\'e}cile and {M}unier, {S}. and {A}ttia, {M}. and de {L}amballerie, {X}. and {F}erry, {T}. and {M}iossec, {P}.}, editor = {}, language = {{ENG}}, abstract = {{S}erological studies of {COVID}-19 convalescent patients have identified polyclonal lineage-specific and cross-reactive antibodies ({A}bs), with varying effector functions against virus variants. {I}ndividual specificities of anti-{SARS}-{C}o{V}-2 {A}bs and their impact on infectivity by other variants have been little investigated to date. {H}ere, we dissected at a monoclonal level neutralizing and enhancing {A}bs elicited by early variants and how they affect infectivity of emerging variants. {B} cells from 13 convalescent patients originally infected by {D}614{G} or {A}lpha variants were immortalized to isolate 445 naturally-produced anti-{SARS}-{C}o{V}-2 {A}bs. {M}onoclonal antibodies (m{A}bs) were tested for their abilities to impact the cytopathic effect of {D}614{G}, {D}elta, and {O}micron ({BA}.1) variants. {N}inety-eight exhibited robust neutralization against at least one of the three variant types, while 309 showed minimal or no impact on infectivity. {T}hirty-eight m{A}bs enhanced infectivity of {SARS}-{C}o{V}-2. {I}nfection with {D}614{G}/{A}lpha variants generated variant-specific (65 neutralizing {A}bs, 35 enhancing {A}bs) and cross-reactive (18 neutralizing {A}bs, 3 enhancing {A}bs) m{A}bs. {I}nterestingly, among the neutralizing m{A}bs with cross-reactivity restricted to two of the three variants tested, none demonstrated specific neutralization of the {D}elta and {O}micron variants. {I}n contrast, cross-reactive m{A}bs enhancing infectivity (n = 3) were found exclusively specific to {D}elta and {O}micron variants. {N}otably, two m{A}bs that amplified in vitro the cytopathic effect of the {D}elta variant also exhibited neutralization against {O}micron. {T}hese findings shed light on functional diversity of cross-reactive {A}bs generated during {SARS}-{C}o{V}-2 infection and illustrate how the balance between neutralizing and enhancing {A}bs facilitate variant emergence.}, keywords = {{COVID}-19 ; {B} cell repertoire ; antibody-dependent enhancement ; human ; monoclonal antibody ; emerging variants}, booktitle = {}, journal = {{E}merging {M}icrobes and {I}nfections}, volume = {13}, numero = {1}, pages = {2307510 [11 p.]}, year = {2024}, DOI = {10.1080/22221751.2024.2307510}, URL = {https://www.documentation.ird.fr/hor/fdi:010089481}, }