Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding

Abstract

Summary Allergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen‐specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non‐specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.

Maternal respiratory sensitization and gestational allergen exposure does not affect subsequent pup responses to homologous or heterologous allergen

“…Maternal sensitization prior to pregnancy has been reported to provide a degree of protection against subsequent pup sensitization to homologous allergen (Fusaro et al, 2002(Fusaro et al, , 2007Victor et al, 2003). Gestational allergen exposure was demonstrated to confer similar protection, especially if dams had also been sensitized prior to breeding (Melkild et al, 2002;Uthoff et al, 2003;Fusaro et al, 2007). In some cases, this protection was attributed to maternal antibody "interference" with neonatal immune responses, as the effects disappeared if pup sensitization was delayed until after maternal antibodies were cleared (Uthoff et al, 2003;Victor et al, 2003).…”

“…Previous studies in mice investigating the effects of maternal sensitization and/or gestational exposure on subsequent pup responses to homologous allergen have produced conflicting results. Maternal sensitization prior to pregnancy has been reported to provide a degree of protection against subsequent pup sensitization to homologous allergen (Fusaro et al, 2002(Fusaro et al, , 2007Victor et al, 2003). Gestational allergen exposure was demonstrated to confer similar protection, especially if dams had also been sensitized prior to breeding (Melkild et al, 2002;Uthoff et al, 2003;Fusaro et al, 2007).…”

“…This method closely mimics the natural exposure scenario, in which allergens (including aerosolized fungal fragments) are typically inhaled (Gorny et al, 2002;Green et al, 2006). In contrast, in the studies described above, dam sensitization was achieved by intraperitoneal (IP) and/or subcutaneous (SC) injection with adjuvant (Herz et al, 2001;Hamada et al, 2003;Uthoff et al, 2003;Victor et al, 2003;Fedulov et al, 2007;Fusaro et al, 2007). Dams were either bred soon thereafter, or a high level of sensitization was maintained by frequent aerosol or intranasal allergen exposures until breeding.…”

Immunotoxicologic analysis of maternal transmission of asthma risk

“…Following sensitization with D pteronyssinus, the offspring of immunized mothers had decreased specific IgE compared to control normal offspring. A more recent study from the same group (Fusaro et al, 2007) demonstrated that 'immunized' mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including IgG in complex with ovalbumin and IgG 1 antibody with "anaphylactic function. "…”

Efeito da imunização materna com Ovalbumina na ativação de células dendríticas e geração de linfócitos T reguladores na prole de camundongos.

“…Este fato salienta que a imunização prévia das mães é um procedimento profilático para evitar a sensibilização precoce das proles (FUSARO et al, 2007).…”