Serum IgA responses against pertussis proteins in infected and Dutch wP or aP vaccinated children: an additional role in pertussis diagnostics

Abstract

Background: Whooping cough is a respiratory disease caused by Bordetella pertussis, which induces mucosal IgA antibodies that appear to be relevant in protection. Serum IgA responses are measured after pertussis infection and might provide an additional role in pertussis diagnostics. However, the possible interfering role for pertussis vaccinations in the induction of serum IgA antibodies is largely unknown.

Methods/principal findings: We compared serum IgA responses in healthy vaccinated children between 1 and 10 years of age with those in children who despite vaccinations recently were infected with Bordetella pertussis. All children have been vaccinated at 2, 3, 4 and 11 months of age with either the Dutch whole-cell pertussis (wP) vaccine or an acellular pertussis (aP) vaccine and additionally received an aP booster vaccination at 4 years of age. Serum IgA responses to pertussis toxin (PT), filamentous heamagglutinin (FHA) and pertactin (Prn) were measured with a fluorescent multiplex bead-based immuno-assay. An ELISPOT-assay was used for the detection of IgA-memory B-cells specific to these antigens. Serum IgA levels to all pertussis vaccine antigens were significantly higher in infected children compared with healthy children. High correlations between anti-PT, anti-FHA or anti-Prn IgA and IgG levels were found in infected children and to some degree in wP primed children, but not at all in aP primed children. Highest numbers of IgA-pertussis-specific memory B-cells were observed after infection and generally comparable numbers were found after wP and aP vaccination.

Conclusions: This study provides new insight in the diagnostic role for serum IgA responses against PT in vaccinated children. Since aP vaccines induce high serum IgG levels that interfere with pertussis diagnostics, serum IgA-PT levels will provide an additional diagnostic role. High levels of serum IgA for PT proved specific for recent pertussis infection with reasonable sensitivity, whereas the role for IgA levels against FHA and Prn in diagnosing pertussis remains controversial.

Figure 1. The number of healthy children per age group.

(A) children primed with the Dutch wP vaccine and (B) children primed with aP vaccines.

Figure 2. IgA levels.

IgA responses specific for PT (A), FHA (B) and Prn (C) for each child in the on the x-axis presented group of children. The red horizontal bars indicate the GMC. The 10 and 28 days post-booster responses are indicated by the black circles and all other groups are indicate by open circles. * significant differences (p<0.05) are indicated for the healthy children between the presented age groups in similar primed children. Differences between infected children and the various groups of healthy wP and aP primed children are described in paragraph 3.1 of the results section.

Figure 3. Correlations between serum IgA and IgG responses.

Spearman correlations and linear regression analysis between serum IgA and serum IgG responses specific for PT, FHA and Prn presented for infected (A), wP (B) and aP (C) primed children.

Figure 4. Correlations between serum IgA-Bp and IgA-PT, -FHA and -Prn in infected children.

Serum IgA-Bp levels are presented on the x-axis and serum IgA-PT (A), -FHA (B) and -Prn (C) on the y-axis.