Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

Abstract

The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.

Protective Levels of Polysaccharide-Specific Maternal Antibodies May Enhance the Immune Response Elicited by Pneumococcal Conjugates in Neonatal and Infant Mice

“…1C and D), and there was a highly significant correlation between maternal and offspring antibody levels in the neonatal (r ϭ shown. These results demonstrate effective transmission of MatAb to the offspring, in agreement with our previous results for pneumococcal and meningococcal PS-specific antibodies (50). The high levels of maternal PPS-1-specific IgG in unimmunized offspring of the Pnc1-TT-immunized mothers declined slowly, ϳ1 log until 9 weeks of age in the neonatal experiment shown and ϳ1 to 1.5 log until 11 weeks of age in the infant experiment.…”

“…All offspring immunized with Pnc1-TT in the absence or presence of MatAb were completely protected against pneumococcal bacteremia, and a great majority were protected against lung infection. As protection against pneumococcal infections is mediated by Abs only, it is important during the time when the offspring are unable to mount adequate Ab responses that MatAbs are above the levels known to be protective (50). Whereas high levels of PPS-1-specific MatAb may protect the offspring during the most vulnerable period, they may also be detrimental, as they can completely inhibit the offspring immune response to the conjugate.…”

“…We have previously shown that MatAb elicited against three important pediatric serotypes can protect neonatal and infant offspring from pneumococcal infections (50), but the effect of MatAb on offspring responses to conjugates of other serotypes was not assessed. For highly versus poorly immunogenic serotypes, it is difficult to predict which levels of MatAb are optimal to provide protection without interfering with the offspring responses.…”

“…We have recently demonstrated that MatAbs elicited by immunization of adult female mice with Pnc-TT of three important pediatric serotypes were able to protect their offspring against pneumococcal infections caused by i.n. challenge with a lethal dose of the homologous pneumococcal serotype (50).…”

Animal Models ofStreptococcus pneumoniaeDisease

“…infection with aspiration set up for adult animals (50) was adjusted to neonatal (1-week-old) and infant (3-week-old) mice, which mimic the immune systems of human neonates and infants, respectively. By using this approach, several aspects of vaccinology in early life were investigated, including the efficacies of polysaccharide conjugate vaccines delivered by the mucosal route (115), the role of T-cell responses to pneumococcal conjugates (116), and the importance of maternal antibodies for protecting offspring against S. pneumoniae (204).…”