Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells.

BACKGROUND: Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. RESULTS: Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specific IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. CONCLUSION: Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

CpG-induced Th1-type response in the downmodulation of early development of allergy and inhibition of B7 expression on T cells of newborn mice.

INTRODUCTION: Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. OBJECTIVE: The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. RESULTS AND DISCUSSION: Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. CONCLUSION: Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.

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

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.