Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells.

Valentina Marcellini,Eva Piano Mortari,Paola Stefanelli,Pasqualina Leone,Elisabetta Pandolfi,Francesco Gesualdo,Fabio Midulla,Alberto Eugenio Tozzi,Rita Carsetti,Giorgio Fedele

doi:10.3389/fimmu.2017.01158

Abstract

Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies.

Highlights

Mammalians protect their progeny during the first days and months of life through the adoptive transfer of maternal antibodies
IgA against PT significantly increased in PERTUSSIS [5.5 (0–39.5)] mothers compared to healthy controls (HCs) [0 (0–0) p = 0.005] and lower respiratory tract infections (LRTI) [0 (0–0) p = 0.01] mothers (Figure 1B)
It has been shown that B. pertussis infects subjects of all ages who act as infection source causing local clusters of disease [28]

Summary

INTRODUCTION

Mammalians protect their progeny during the first days and months of life through the adoptive transfer of maternal antibodies. We found that mothers that are not infected or exposed to pertussis (HC and LRTI) have low levels of pertussis-specific antibodies in the serum and breast milk and are unable to transfer passive protection to their children before or after birth. Mothers of children with pertussis actively protect themselves from the ongoing infection by increasing the number of specific memory B cells that secrete IgG and IgA and producing anti-pertussis toxin IgG and IgA antibodies in the serum. IgM memory B cells secreting antibodies able to react with pertussis antigens and Bordetella-binding milk IgA increase, in mothers of children with pertussis and in the mothers of neonates with LRTI. Whereas switched memory B cells and serum IgA and IgG increase in response to pertussis, IgM memory B cells and milk IgA are aspecifically induced during infection generating a wide spectrum antibody response. A p-value of less than 0.05 was considered as statistically significant

RESULTS

DISCUSSION

ETHICS STATEMENT