Abstract
Newborns and unvaccinated infants, compared to other age groups, are more susceptible to pertussis infection, manifesting severe symptoms leading to a higher mortality. The recent increase in pertussis cases demands more effective strategies to overcome this major health problem. In parallel with maternal-immunization, neonatal-immunization (NI) is a strategy needing revision. Here, using the intranasal-challenge-mouse-model we evaluated the protective capacity of NI in both naïve-mice and those with maternally acquired immunity. We tested our acellular-vaccine-candidate based on outer-membrane-vesicles derived from Bordetella pertussis (OMVP) that induces Th2-profile but also the recommended Th-profile for protection: Th1/Th17-profile and CD4 T-memory-cells that reside in the lungs. Commercial acellular-vaccine (aP) and whole cell-vaccine (wP) inducing mainly Th2-profile and Th1-profile, respectively, were also tested. Analyzing the induced immunity and protection capability of NI included in 1- or 2-dose schedules with the same or different types of vaccine, we detected that the aP-vaccine administered in either single- or 2-dose schedules protected against sublethal B. pertussis infection. Schedules consisting of doses of aP neonatally and of OMVP or wP vaccine during infancy greatly reduced bacterial lung colonization while inducing the highest levels of high-avidity anti-pertussis toxin (PTx) IgG. That OMVP or wP neonatal dose did not interfere with the protection of transferred maternal immunity was especially encouraging. Moreover, OMVP- or wP used as a neonatal dose enhanced the quality of the humoral immune response in immunized pups. Antibodies generated by OMVP-or wP-vaccinated mice born to aP-immunized mothers were of higher avidity than those from mice that harbored only maternal immunity; but when mothers and neonates were immunized with the same aP-vaccine, the humoral response in the neonates was partially suppressed through the blunting of the level of anti-PTx IgG induced by the neonatal aP dose. These results demonstrated that neonatal immunization is a possible strategy to be considered to improve the current pertussis epidemiology. For neonates without maternal-immunity, mixed-vaccination schedules that include the aP- and OMVP-vaccines appear to be the most appropriate to induce protection in the pups. For offspring from immune mothers, to avoid blunting-effect, NI should be carried out with vaccines other than those applied during pregnancy.
Highlights
The first month of life represents one of the most vulnerable periods for contracting infectious diseases that can be fatal to neonates
Experiments involving the 2-dose–vaccination schedule in which one dose was administered at 7 days of age and the second at infancy (21 days of age) in comparison with schedules that included a single dose at infancy indicated that neonatal vaccination did not interfere with the eventual protection induced by the primary vaccination (Figure 2)
In the study reported here, we used a mouse model to analyze whether neonatal immunization with pertussis vaccines that induce different Th-profiles—an OMVP-based vaccine giving rise to a Th1/Th2/Th17 mixed response, the aP resulting in mainly Th2, and the wP inducing Th1/Th17—led to a protection of offspring against B. pertussis
Summary
The first month of life represents one of the most vulnerable periods for contracting infectious diseases that can be fatal to neonates. Some of the diseases that affect that age group are vaccine preventable, but the majority of the infants who die are not old enough to receive the number of vaccine doses required for inducing protection Within this context, and in an effort to reverse this serious health problem, maternal immunization was implemented as a possible solution for various pathogens (Munoz et al, 2018). Maternal pertussis immunization during the third trimester of every pregnancy (27–36 weeks of gestation) is one of the recent strategies recommended in several countries to improve pertussis control in newborns and older infants (Healy, 2016; Hoang et al, 2016) The rationale for this strategy is that mothers are detected as the main source of infection for unprotected infants, who are at high risk of complications and death, and that antibody-mediated immunity is achieved by placental transfer and breast-feeding (Cherry, 2016). Baxter et al (2017) found that maternal immunization provided additional protection for infants who received the first dose of pertussis vaccine
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