The level and duration of RSV-specific maternal IgG in infants in Kilifi Kenya

Abstract

Background: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants. The rate of decay of RSV-specific maternal antibodies (RSV-matAb), the factors affecting cord blood levels, and the relationship between these levels and protection from infection are poorly defined.

Methods: A birth cohort (n = 635) in rural Kenya, was studied intensively to monitor infections and describe age-related serological characteristics. RSV specific IgG antibody (Ab) in serum was measured by the enzyme linked immunosorbent assay (ELISA) in cord blood, consecutive samples taken 3 monthly, and in paired acute and convalescent samples. A linear regression model was used to calculate the rate of RSV-matAb decline. The effect of risk factors on cord blood titres was investigated.

Results: The half-life of matAb in the Kenyan cohort was calculated to be 79 days (95% confidence limits (CL): 76-81 days). Ninety seven percent of infants were born with RSV-matAb. Infants who subsequently experienced an infection in early life had significantly lower cord titres of anti-RSV Ab in comparison to infants who did not have any incident infection in the first 6 months (P = 0.011). RSV infections were shown to have no effect on the rate of decay of RSV-matAb.

Conclusion: Maternal-specific RSV Ab decline rapidly following birth. However, we provide evidence of protection against severe disease by RSV-matAb during the first 6-7 months. This suggests that boosting maternal-specific Ab by RSV vaccination may be a useful strategy to consider.

Figure 1. Schema of sample collection regime for Kilifi cohort.

635 children were recruited to a birth cohort in 2 phases (February- May 2002, and December 2002- May 2003). Cord bloods (circles), together with sera every 3 months (triangles) were collected. Any antigen positive nasal washing detected by IFAT collected upon each ARI episode, prompted collection of paired acute (asterix) and convalescent (squares) phase sera. The first 2 epidemics experienced by the cohort are indicated by the black bars.

Figure 2. The level of RSV-specific matAb by age (months) in a birth cohort, Kilifi Kenya.

Box plot of log₁₀AU Ab levels for age categories defined as 0 months (cord), 0.5 (>0-<1), 1.5 (1-<2), 2.5 (2-<3), 3.5 (3-<4), 4.5 (4-<5) and 5.5 (5-<6) months. The red horizontal line defines the cut-off for seropositivity of 1.5 log₁₀AU.

Figure 3. Frequency distribution of antibody titres (log₁₀ AU) by age class (months).

Cut-off between seropositive and seronegative is shown by red lines and lies between 1.5–1.8 (log₁₀AU).

Figure 4. Age-seroprevalence profile at various cut-off levels of seropositivity.

The assay cut-off value of seropositivity is 1.5.

Figure 5. Scatter plot of Ab titres (log₁₀ AU) during the first 6 months of life.

The predicted line of fit by simple linear regression: y = mx+c (rate of decay (slope), m = −0.008; intercept, c = 2.928) is indicated. Only children without serologic evidence of infection during the first 6 months of life are depicted.