Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life

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 ma...

Descripción completa

Detalles Bibliográficos
Autores principales: Aispuro, Pablo Martín, Ambrosis, Nicolás Martín, Zurita, María Eugenia, Gaillard, María Emilia, Bottero, Daniela, Hozbor, Daniela Flavia
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Ciencias Exactas
Neonatal Mouse
Vaccine
Pertussis infection
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107813
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7182080&blobtype=pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-107813
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Neonatal Mouse
Vaccine
Pertussis infection
spellingShingle Ciencias Exactas
Neonatal Mouse
Vaccine
Pertussis infection
Aispuro, Pablo Martín
Ambrosis, Nicolás Martín
Zurita, María Eugenia
Gaillard, María Emilia
Bottero, Daniela
Hozbor, Daniela Flavia
Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
topic_facet Ciencias Exactas
Neonatal Mouse
Vaccine
Pertussis infection
description 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.
format Articulo
Articulo
author Aispuro, Pablo Martín
Ambrosis, Nicolás Martín
Zurita, María Eugenia
Gaillard, María Emilia
Bottero, Daniela
Hozbor, Daniela Flavia
author_facet Aispuro, Pablo Martín
Ambrosis, Nicolás Martín
Zurita, María Eugenia
Gaillard, María Emilia
Bottero, Daniela
Hozbor, Daniela Flavia
author_sort Aispuro, Pablo Martín
title Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
title_short Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
title_full Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
title_fullStr Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
title_full_unstemmed Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life
title_sort use of a neonatal-mouse model to characterize vaccines and strategies for overcoming the high susceptibility and severity of pertussis in early life
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/107813
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7182080&blobtype=pdf
work_keys_str_mv AT aispuropablomartin useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
AT ambrosisnicolasmartin useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
AT zuritamariaeugenia useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
AT gaillardmariaemilia useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
AT botterodaniela useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
AT hozbordanielaflavia useofaneonatalmousemodeltocharacterizevaccinesandstrategiesforovercomingthehighsusceptibilityandseverityofpertussisinearlylife
bdutipo_str Repositorios
_version_ 1764820443666055168

Ejemplares similares