The impact of timing of maternal influenza immunization on infant antibody levels at birth

Abstract

Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunization is a potent tool to protect both these at-risk groups. While the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunized in the second trimester of pregnancy had the highest antibody titres compared to children immunized in the third trimester. The aim of the current study was to investigate how the timing of maternal influenza immunization impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both immunoglobulin (Ig)G-binding enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunization was performed less than 4 weeks before birth. These studies confirm that immunization during pregnancy increases the antibody titre in infants. Importantly, antibody levels in cord blood were significantly higher when the mother was vaccinated in either trimesters 2 or 3, although titres were significantly lower if the mother was immunized less than 4 weeks before birth. Based on these data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available.

Keywords: human; vaccination; viral.

Figure 1

Effect of maternal immunization on maternal and cord enzyme‐linked immunosorbent assay (ELISA) titres. Blood was collected from mothers and cord at the time of delivery. Donors were grouped by vaccination status of the mother. Antibody titre to H1N1 influenza by ELISA in all individuals (a), or in cord (b) and maternal samples (c) by stage of pregnancy at immunization. Haemagglutination inhibition assay (HAI) titres to H1N1 influenza (d); the dotted line represents the level of seroprotection (HAI titre ≥ 1 : 40). Numbers above are the proportion of individuals who sero‐converted. HAI titres by stage of pregnancy at immunization in cord (e) and maternal samples (f). One‐way analysis of variance (anova) and Bonferroni’s test: a,d, comparison between all groups; b,c,e,f, comparisons against the unvaccinated group. Line represents the mean, ^* P < 0·05, ^** P ≤ 0·01, ^*** P ≤ 0·001.

Figure 2

The effect of time interval between maternal vaccination and delivery on anti‐influenza titres. Individuals were grouped by the time interval between vaccination and delivery. H1N1‐specific immunoglobulin (Ig)G titres were measured by enzyme‐linked immunosorbent assay (ELISA) in cord (a) and maternal serum (b). H1N1‐specific HAI titre was measured by haemagglutination inhibition assay (HAI) assay in cord (c) and maternal (d) serum samples. The dotted line represents the level of seroprotection (HAI titre ≥ 1 : 40). One‐way analysis of variance (anova) and Bonferroni’s test: comparisons between all groups and the unvaccinated and 0–4 groups. Line represents the mean, ^* P < 0·05, ^** P ≤ 0·01, ^*** P ≤ 0·001.

Figure 3

Effect of season of birth and immunization on antibody titre in mother and cord. Maternal and cord samples were grouped by the season of birth comparing those in the influenza season (born September–March) to those outside it (April–August). Antibody titres were compared by birth season in unvaccinated (a) and unvaccinated donors (b). Titres in unvaccinated (c) and vaccinated (d) groups were compared against month of birth, ordered from the start of the influenza season (September). Month of vaccination (e) and month of birth (f) for children born to mothers vaccinated in different trimesters. One‐way analysis of variance (anova) and Bonferroni’s test: a,b, pairwise comparison between cord and maternal groups; line represents the mean, ^* P < 0·05, ^** P ≤ 0·01, ^*** P ≤ 0·001.

Figure 4

Effect of maternal immunization on maternal and cord enzyme‐linked immunosorbent assay (ELISA) titres to H3N2 and B antigens. Blood was collected from mothers and cord at the time of delivery. Donors were grouped by vaccination status of the mother. Antibody titre to H1N1 influenza by ELISA in all individuals (a) or in cord (b) and maternal samples (c) by stage of pregnancy at immunization. Antibody titre to B influenza by ELISA in all individuals (d) or in cord (e) and maternal samples (f) by stage of pregnancy at immunization. Maternal (∆) and cord (●) samples were grouped by the season of birth comparing titres to H3N2 (g) or influenza B (h) in the influenza season (born September–March, closed symbols) to those outside it (April‐August, open symbols). One‐way analysis of variance (anova) and Bonferroni’s test: a,d, comparison between all groups; b,c,e,f, comparisons against unvaccinated group; g,h, pairwise comparison between cord and maternal groups. Line represents the mean, ^*  P < 0·05.