Development and validation of the in vitro microfold cell model to investigate the role of breastmilk antibodies in infant protection against pertussis.

Pertussis (better known as whooping cough) is a vaccine-preventable respiratory tract infection mostly affecting infants who are too young to be protected by the currently available vaccines. To better protect these infants, pertussis vaccination during pregnancy has been introduced in a lot of countries worldwide. Vaccination with a tetanus, diphtheria, acellular pertussis vaccine raises the titer of disease-specific maternal antibodies in pregnant women which are then transferred to the newborn through transplacental transport and breastfeeding thereby providing passive protection to the infant in the first vulnerable weeks of life. Little evidence suggests that the antibodies ingested by the newborn via breastmilk provide local mucosal immunity in the enteric and respiratory tract, but whether they can actually be transported across the infant gut barrier into the circulation of the newborn possibly providing systemic protection is currently unexplored. The proposed project aims to develop and validate an in vitro microfold (M) cell model that mimics the infant gut barrier, to investigate the transport of secretory IgA (sIgA) antibodies in breastmilk from the enteric and respiratory tract into the systemic circulation. For this purpose, Caco-2 cells and Raji cells will be co-cultured on a transwell to form M cells, and the formation of M cells will be investigated with confocal microscopy. To validate the model, total sIgA antibodies in a limited number of breastmilk samples will be measured using ELISA before and after diffusion through the model. Once validated, total and pertussis-specific sIgA antibodies in breastmilk samples will be measured on a larger scale to determine the mucosal transport of antibodies across the infant gastrointestinal and respiratory tract . This model could be an effective and low-cost tool that contributes to exploring the impact of vaccination during pregnancy on protection provided by lactation. The project might also be the basis of more research within this field in the context of other immunoglobulins of importance and other infectious diseases for which vaccines can be administered during pregnancy.

Keywords:VACCINOLOGY, PERTUSSIS ANTIBODIES, BREASTFEEDING

Disciplines:Vaccinology