Features and protective efficacy of human mAbs targeting Mycobacterium tuberculosis arabinomannan
A better understanding of the epitopes most relevant for antibody-mediated protection against tuberculosis (TB) remains a major knowledge gap. We have shown that human polyclonal IgG against the Mycobacterium tuberculosis (M. tuberculosis) surface glycan arabinomannan (AM) and related lipoarabinomannan (LAM) is protective against TB. To investigate the impact of AM epitope recognition and Fcγ receptor (FcγR) binding on antibody functions against M. tuberculosis, we isolated a high-affinity human monoclonal antibody (mAb; P1AM25) against AM and showed its binding to oligosaccharide (OS) motifs we previously found to be associated with in vitro functions of human polyclonal anti-AM IgG. Human IgG1 P1AM25, but not 2 other high-affinity human IgG1 anti-AM mAbs reactive with different AM OS motifs, enhanced M. tuberculosis phagocytosis by macrophages and reduced intracellular growth in an FcγR-dependent manner. P1AM25 in murine IgG2a, but neither murine IgG1 nor a non-FcγR-binding IgG, given intraperitoneally prior to and after aerosolized M. tuberculosis infection, was protective in C57BL/6 mice. Moreover, we demonstrated the protective efficacy of human IgG1 P1AM25 in passive transfer with M. tuberculosis-infected FcγR-humanized mice. These data enhance our knowledge of the important interplay between both antibody epitope specificity and Fc effector functions in the defense against M. tuberculosis and could inform development of vaccines against TB.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
JCI insight - 8(2023), 20 vom: 23. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Yanyan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
53026-40-7 |
|---|
| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 10.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1172/jci.insight.167960 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM362301336 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM362301336 | ||
| 003 | DE-627 | ||
| 005 | 20240210232645.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/jci.insight.167960 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1286.xml |
| 035 | |a (DE-627)NLM362301336 | ||
| 035 | |a (NLM)37733444 | ||
| 035 | |a (PII)e167960 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Yanyan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Features and protective efficacy of human mAbs targeting Mycobacterium tuberculosis arabinomannan |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.11.2023 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A better understanding of the epitopes most relevant for antibody-mediated protection against tuberculosis (TB) remains a major knowledge gap. We have shown that human polyclonal IgG against the Mycobacterium tuberculosis (M. tuberculosis) surface glycan arabinomannan (AM) and related lipoarabinomannan (LAM) is protective against TB. To investigate the impact of AM epitope recognition and Fcγ receptor (FcγR) binding on antibody functions against M. tuberculosis, we isolated a high-affinity human monoclonal antibody (mAb; P1AM25) against AM and showed its binding to oligosaccharide (OS) motifs we previously found to be associated with in vitro functions of human polyclonal anti-AM IgG. Human IgG1 P1AM25, but not 2 other high-affinity human IgG1 anti-AM mAbs reactive with different AM OS motifs, enhanced M. tuberculosis phagocytosis by macrophages and reduced intracellular growth in an FcγR-dependent manner. P1AM25 in murine IgG2a, but neither murine IgG1 nor a non-FcγR-binding IgG, given intraperitoneally prior to and after aerosolized M. tuberculosis infection, was protective in C57BL/6 mice. Moreover, we demonstrated the protective efficacy of human IgG1 P1AM25 in passive transfer with M. tuberculosis-infected FcγR-humanized mice. These data enhance our knowledge of the important interplay between both antibody epitope specificity and Fc effector functions in the defense against M. tuberculosis and could inform development of vaccines against TB | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antigen | |
| 650 | 4 | |a Immunoglobulins | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Infectious disease | |
| 650 | 4 | |a Tuberculosis | |
| 650 | 7 | |a arabinomannan |2 NLM | |
| 650 | 7 | |a 53026-40-7 |2 NLM | |
| 650 | 7 | |a Receptors, IgG |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 700 | 1 | |a Chen, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yongqi |e verfasserin |4 aut | |
| 700 | 1 | |a Furey, Aisha |e verfasserin |4 aut | |
| 700 | 1 | |a Lowary, Todd L |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, John |e verfasserin |4 aut | |
| 700 | 1 | |a Bournazos, Stylianos |e verfasserin |4 aut | |
| 700 | 1 | |a Ravetch, Jeffrey V |e verfasserin |4 aut | |
| 700 | 1 | |a Achkar, Jacqueline M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JCI insight |d 2016 |g 8(2023), 20 vom: 23. Okt. |w (DE-627)NLM257703918 |x 2379-3708 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2023 |g number:20 |g day:23 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/jci.insight.167960 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2023 |e 20 |b 23 |c 10 | ||