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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Impact of maternal whole-cell or acellular pertussis primary immunization on neonatal immune response
Pablo Martin Aispuro1, Daniela Bottero1, María Eugenia Zurita1
1Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CONICET, La Plata, Argentina.
Insights
Maternal immunization with whole-cell pertussis vaccine (wP) priming followed by acellular pertussis vaccine (aP) during pregnancy offers longer-lasting protection for infants against pertussis compared to aP-only priming.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Pertussis (whooping cough) remains a global public health concern, necessitating effective immunization strategies.
- Maternal immunization programs aim to protect infants during their vulnerable early months.
- The choice between whole-cell pertussis vaccine (wP) and acellular pertussis vaccine (aP) for priming and during pregnancy is critical for optimal disease control.
Purpose of the Study:
- To compare the impact of different maternal pertussis vaccination priming schedules (wP-wP-aPpreg vs. aP-aP-aPpreg) on immune responses and offspring protection against Bordetella pertussis.
- To evaluate the duration of maternal immunity conferred by these schedules.
- To investigate potential interference between maternal and neonatal vaccination in offspring.
Main Methods:
- Mice were immunized using two maternal vaccination schemes: wP-wP-aPpreg and aP-aP-aPpreg.
- Immune responses (PTx-specific IgG) were measured in mothers and offspring.
- Offspring protection against B. pertussis challenge was assessed.
- The timing of birth relative to maternal aPpreg vaccination was analyzed.
Main Results:
- Both schedules induced pertussis toxin (PTx)-specific IgG in mothers, with sustained levels in the wP-wP-aPpreg group but a decline in the aP-aP-aPpreg group after 22 weeks.
- The wP-wP-aPpreg scheme induced a mixed Th1/Th2 immune response, while aP-aP-aPpreg induced a predominantly Th2 response.
- Offspring protection was longer-lasting with the wP-wP-aPpreg schedule, maintaining high IgG levels up to 22 weeks post-maternal vaccination, whereas aP-aP-aPpreg protection waned after 18 weeks.
- Neonatal vaccination in aP-aP-aPpreg offspring potentially interfered with maternal immunity, increasing susceptibility to B. pertussis infection.
Conclusions:
- Whole-cell pertussis vaccine (wP) priming followed by acellular pertussis vaccine (aP) during pregnancy provides more durable maternal immunity and offspring protection against pertussis than an acellular-only schedule.
- The wP-wP-aPpreg schedule supports a more robust and sustained immune response, crucial for protecting infants.
- Potential interference between maternal and neonatal pertussis vaccination warrants further investigation, especially with acellular vaccine priming.
Abstract:
With the introduction of pertussis immunization for pregnant women in many countries, there has been renewed interest in the impact of whole-cell pertussis vaccine (wP) versus acellular vaccine (aP) on disease control, particularly regarding the best approach for priming. To gather evidence on this topic, we analyzed the impact of aP or wP priming on aP vaccination during pregnancy (aPpreg) in mice. Two-mother vaccination schemes were employed (wP-wP-aPpreg and aP-aP-aPpreg), and the immune response in the mothers and their offspring, as well as the protection of the offspring against Bordetella pertussis challenge, were assessed. Pertussis toxin (PTx)-specific IgG responses were detected in mothers after both the second and third doses, with higher titers after the third dose, regardless of the vaccination schedule. However, a significant reduction in PTx-IgG levels was observed after 22 weeks post aPpreg immunization in mothers with the aP-aP-aPpreg scheme but not in the wP-wP-aPpreg immunized mothers. The aP-aP-aPpreg schedule triggered a murine antibody response mainly to a Th2-profile, while wP-wP-aPpreg induced a Th1/Th2 mixed profile. Both immunization schemes administered to the mothers protected the offspring against pertussis, but the wP-wP-aPpreg vaccination conferred offspring protection in all pregnancies at least up to 20 weeks after receiving the aPpreg-dose. In contrast, the immunity induced by aP-aP-aPpreg began to decline in births that occurred 18 weeks after receiving the aPpreg dose. For the aP-aP-aPpreg scheme, pups born from gestations furthest from aPpreg (+22 weeks) had lower PTx-specific IgG levels than those born closer to the application of the dose during pregnancy. In contrast, for pups born to wP-wP-aPpreg vaccinated mothers, the PTx-specific IgG levels were maintained over time, even for those born at the longest time studied (+22 weeks). It is noteworthy that only the pups born from mothers with aP-aP-aPpreg and receiving a neonatal dose of either aP or wP were more susceptible to B. pertussis infection than mice with only maternal immunity, suggesting interference with the induced immunity (p<0.05). However, it should be noted that mice with maternal immunity, whether vaccinated or not with neonatal doses, are better protected against colonization with B. pertussis than mice without maternal immunity but vaccinated with aP or wP.
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