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. 2018 Jun 20;218(2):208-217.
doi: 10.1093/infdis/jiy106.

Virus-Specific Antibody, Viral Load, and Disease Severity in Respiratory Syncytial Virus Infection

Edward E Walsh  1   2 , Lu Wang  3 , Ann R Falsey  1   2 , Xing Qiu  3 , Anthony Corbett  3 , Jeanne Holden-Wiltse  3 , Thomas J Mariani  4   5   6 , David J Topham  7 , Mary T Caserta  6
Affiliations

Virus-Specific Antibody, Viral Load, and Disease Severity in Respiratory Syncytial Virus Infection

Edward E Walsh et al. J Infect Dis. .

Abstract

Background: Maternally derived serum antibody and viral load are thought to influence disease severity in primary respiratory syncytial virus (RSV) infection. As part of the AsPIRES study of RSV pathogenesis, we correlated various serum antibody concentrations and viral load with disease severity.

Methods: Serum neutralizing antibody titers and levels of immunoglobulin G (IgG) to RSV fusion protein (F), attachment proteins of RSV group A and B, the CX3C region of G, and nasal viral load were measured in 139 full-term previously healthy infants with primary RSV infection and correlated with illness severity.

Results: Univariate analysis showed no relationship between measures of serum antibody and severity. However, a multivariate model adjusting for age at the time of infection found a significant 0.56 decrease in severity score for each 2-fold increase in antibody concentration to RSV F. The benefit of antibody was greatest in infants ≤ 2 months of age. Additionally, estimated antibody titer at birth was correlated with age at infection, suggesting that higher antibody titers delay infection. Viral load did not differ by illness severity.

Conclusion: Our data support the concept of maternal immunization with an RSV vaccine during pregnancy as a strategy for reducing the burden of RSV infection in full-term healthy infants exposed to RSV during their first winter.

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Figures

Figure 1.
Figure 1.
Relationship of the global respiratory severity score (GRSS) and anti–respiratory syncytial virus (RSV) antibody titers. Reported slope P values were calculated by a regression t test. A, Antibody to RSV fusion protein (F) for all infants. B, Antibody to attachment protein of group A RSV (Ga) for group A infections (Ga_A). C, Neutralizing antibody to group A RSV for group A infection (MNA_A). D, Relationship between GRSS and age at time of infection.
Figure 2.
Figure 2.
Relationship of antibody titers and age at the time of infection. Disease severity was categorized as mild (global respiratory severity score [GRSS] ≤ 3.5; open circles) or severe (GRSS > 3.5; closed circles). Reported ρ and P values were calculated by the Spearman correlation test. A, Antibody to respiratory syncytial virus (RSV) fusion protein (F). B, Antibody to attachment protein of group A RSV (Ga) for group A virus infection (Ga_A). C, Neutralizing antibody to group A RSV for group A infection (MNA_A). D, Neutralizing antibody to group B RSV for group B infection (MNA_B).
Figure 3.
Figure 3.
Relationship between antibody titer and severity (global respiratory severity score [GRSS]) for infants ≤ 2 months of age. GRSS is plotted against antibody to respiratory syncytial virus (RSV) fusion protein (F) for infants 0.5–1.0 months of age (A) and infants 1.1–2.0 months of age (B) and against neutralizing antibody for group A RSV infections (MNA_A) for the same age groups (C and D).
Figure 4.
Figure 4.
Relationship of estimated antibody titers at birth and time to respiratory syncytial virus (RSV) infection in mild (global respiratory severity score [GRSS] ≤ 3.5; open circles) or severe (GRSS > 3.5; closed circles) illness. The estimated antibody titer at birth is plotted against the age at which RSV infection was identified. Reported ρ and P values were calculated by the Spearman correlation test. A, Antibody to RSV fusion protein (F). B, Antibody to attachment protein of group A RSV (Ga) for group A virus infection (Ga_A). C, Antibody to attachment protein of group B RSV (Gb) for group A virus infection (Ga_B).
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