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.
Highlights
Neutralizing antibodies to HIV-1 are of particular interest for vaccine-mediated humoral immunity
Study population clinical characteristics Children were categorized by age, as per the antiretroviral therapy (ART) initiation WHO guidelines at the time of study [28] (Table 1)
HIV-specific antibody neutralization activity Neutralization breadth was determined for 44 children against a globally representative panel of 12 viruses
Summary
Neutralizing antibodies (bNAbs) to HIV-1 are of particular interest for vaccine-mediated humoral immunity. Only a small proportion of HIV-infected individuals generate bNAbs [7] and no HIV vaccine candidate has been able to elicit antibodies with sufficient breadth [8,9]. Antibody functions have largely been described in adults but less is known for children despite their distinct course of HIV infection. AIDS typically develops more rapidly in paediatric HIV cases compared with adults [10,11,12] and infants and children rapidly develop broader and more potent neutralizing antibodies than adults [13,14,15]. An isolated bNAb from an infant showed low somatic hypermutation and lacked insertions and deletions typical of bNAbs from adults, suggesting that infants may have a more direct pathway to breadth that does not require years of affinity maturation [13]
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