Nduati, EW;
Gorman, MJ;
Sein, Y;
Hermanus, T;
Yuan, D;
Oyaro, I;
Muema, DM;
... Moore, PL; + view all
(2021)
Coordinated Fc-effector and neutralization functions in HIV-infected children define a window of opportunity for HIV vaccination.
AIDS
, 35
(12)
pp. 1895-1905.
10.1097/QAD.0000000000002976.
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Abstract
OBJECTIVES: Antibody function has been extensively studied in HIV-infected adults but is relatively understudied in children. Emerging data suggests enhanced development of broadly neutralizing antibodies (bNAbs) in children but Fc effector functions in this group are less well defined. Here, we profiled overall antibody function in HIV-infected children. DESIGN: Plasma samples from a cross-sectional study of 50 antiretroviral therapy-naive children (aged 1-11 years) vertically infected with HIV-1 clade A were screened for HIV-specific binding antibody levels and neutralizing and Fc-mediated functions. METHODS: Neutralization breadth was determined against a globally representative panel of 12 viruses. HIV-specific antibody levels were determined using a multiplex assay. Fc-mediated antibody functions measured were antibody-dependent: cellular phagocytosis (ADCP); neutrophil phagocytosis (ADNP); complement deposition (ADCD) and natural killer function (ADNK). RESULTS: All children had HIV gp120-specific antibodies, largely of the IgG1 subtype. Fifty-four percent of the children exhibited more than 50% neutralization breadth, with older children showing significantly broader neutralization activity. Apart from ADCC, observed only in 16% children, other Fc-mediated functions were common (>58% children). Neutralization breadth correlated with Fc-mediated functions suggesting shared determinants of enhanced antibody function exist. CONCLUSIONS: These results are consistent with previous observations that children may develop high levels of neutralization breadth. Furthermore, the striking association between neutralization breadth and Fc effector function suggests that HIV vaccination in children could yield multifunctional antibodies. Paediatric populations may therefore provide an ideal window of opportunity for HIV vaccination strategies.
| Type: | Article |
|---|---|
| Title: | Coordinated Fc-effector and neutralization functions in HIV-infected children define a window of opportunity for HIV vaccination |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1097/QAD.0000000000002976 |
| Publisher version: | http://doi.org/10.1097/QAD.0000000000002976 |
| Language: | English |
| Additional information: | Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Antibodies, children, Fc-mediated function, HIV, neutralizing function, vaccines |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10136494 |
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