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. 2017 Dec 12;216(11):1398-1406.
doi: 10.1093/infdis/jix489.

Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection

Cristina Capella  1 , Supranee Chaiwatpongsakorn  1 , Erin Gorrell  1 , Zachary A Risch  1 , Fang Ye  1 , Sara E Mertz  1 , Sara M Johnson  1 , Melissa Moore-Clingenpeel  2 , Octavio Ramilo  1   3 , Asuncion Mejias  1   3 , Mark E Peeples  1   3
Affiliations

Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection

Cristina Capella et al. J Infect Dis. .

Abstract

Background: Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory tract infection in infants. Maternally derived RSV-specific antibodies play a role in protection against RSV infection in early life, but data regarding the concentration and specificity of those antibodies are incomplete.

Methods: We prospectively enrolled a cohort of previously healthy infants and young children hospitalized (n = 45) or evaluated as outpatients (n = 20) for RSV infection, and healthy noninfected age-matched controls (n = 18). Serum samples were obtained at enrollment to quantify the concentrations and neutralizing activity of serum immunoglobulin G antibodies to the RSV prefusion (pre-F), postfusion (post-F), and G glycoproteins. We also assessed the associations between antibody concentrations and clinical disease severity.

Results: Concentrations of pre-F antibodies were ≥3-fold higher than post-F antibodies and >30-fold higher than G antibodies in serum from infants with acute RSV infection. Antibody concentrations and neutralizing activity inversely correlated with age. The pre-F antibodies displayed the greatest neutralizing activity (55%-100%), followed by G (0%-45%), and post-F (0%-29%) antibodies. Higher concentrations of pre-F and G antibodies, but not post-F antibodies, were associated with lower clinical disease severity scores.

Conclusions: Maternal antibodies directed to pre-F, followed by antibodies directed to G, can modulate RSV disease severity in young infants.

Keywords: RSV; antibodies; infant; prefusion; severity.

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Figures

Figure 1.
Figure 1.
Serum immunoglobulin (Ig)G to each respiratory syncytial virus (RSV) neutralizing antigen and total neutralizing activity according to age. Sera from children <2 years of age with acute RSV infection (n = 65; 45 hospitalized and 20 outpatients) and from healthy controls (n = 18) were analyzed for IgG antibody binding and neutralization activity, according to age (expressed in months). Antibodies to (A) the pre-F protein, (B) the post-F protein, and (C) the G protein were quantified by enzyme-linked immunosorbent assay or (D) assessed for neutralization activity. Neutralization is shown as the half-maximal (50%) inhibitory concentration of serum required to inhibit RSV infection. Each symbol represents the median of triplicate values, for each individual patient serum sample. Antibody concentrations are expressed as micrograms of antigen-specific IgG per milliliter of serum. Note that scales are different for each RSV glycoprotein.
Figure 2.
Figure 2.
Relationship between clinical disease severity, antibody concentration, and neutralizing activity in patients with acute respiratory syncytial virus infection. Patients were categorized into mild (clinical disease severity score [CDSS] 0–5; low) and severe (CDSS 6–15; high), and their serum antibody concentrations were plotted: (A) pre-F; (B) post-F; (C) G; and (D) neutralizing activity. P values were determined by the Mann-Whitney test. Abbreviation: Ig, immunoglobulin.
Figure 3.
Figure 3.
Protein-specific targets of neutralizing antibody in patient sera. The sera from 16 respiratory syncytial virus (RSV)-infected hospitalized infants were adsorbed with each of the 3 viral proteins before measuring their remaining neutralizing activity. (A) Pre-F protein (blue), post-F protein (red), or G protein (green). Neutralization (%) indicates the percentage of original neutralizing activity removed by adsorption with the indicated protein. (B) The unadsorbed sera from the 16 RSV-infected patients were further analyzed by enzyme-linked immunosorbent assay to determine antibody avidity. P value was calculated by Kruskal-Wallis followed by Dunn’s multiple comparisons test. Abbreviation: ns, not significant.
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