Maternal Immunization: New Perspectives on Its Application Against Non-Infectious Related Diseases in Newborns

Abstract

The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection against various life-threatening diseases in pregnant women and their children. A number of studies to improve prevention rates and expand protection against the largest possible number of infections are still in progress. The complex unicity of the mother-infant interaction, both during and after pregnancy and which involves immune system cells and molecules, is an able partner in the success of maternal immunization, as intended thus far. Interestingly, new studies have shed light on the versatility of maternal immunization in protecting infants from non-infectious related diseases, such as allergy, asthma and congenital metabolic disorders. However, barely any attempt at applying maternal immunization to the prevention of childhood cancer has been made. The most promising study reported in this new field is a recent proof of concept on the efficacy of maternal immunization in protecting cancer-prone offspring against mammary tumor progression. New investigations into the possibility of exploiting maternal immunization to prevent the onset and/or progression of neuroblastoma, one of the most common childhood malignancies, are therefore justified. Maternal immunization is presented in a new guise in this review. Attention will be focused on its versatility and potential applications in preventing tumor progression in neuroblastoma-prone offspring.

Keywords: DNA vaccination; cancer prevention; childhood cancer; maternal immunization; neuroblastoma.

Figure 1

Schematic representation of the mechanism underlying maternal immunization-induced immune protection in offspring. (A) Maternal immunization schedule providing a prime-boost DNA electrovaccination strategy in BALB/c female mice, which then mated with a transgenic BALB-neuT male. (B) Maternal DNA immunization leads to high levels of anti-neu IgG antibodies in mother’s sera being passed to offspring mainly through colostrum and milk. Maternally-derived IgG alone, or complexed with the EC portion of neu, bind the FcRn on the surface of the pup’s enterocytes. The antibody-receptor complex can be internalized and then released into the intestinal lumen. The IgG-neu ICs interact with DC through Fcγ receptors. The DC can then internalize the ICs and load neu peptides onto the MHC-I or MHC-II. The binding of CD8⁺ T cells that express specific TCR against p63-71 with the MHC-I-neu peptide complex on DCs leads to the expansion of this specific CD8⁺ T cell clone into the lymph nodes of offspring born from and fed by anti-neu vaccinated mothers, activating an effective cytotoxic T cell response. (C) List of pictures and related abbreviations.

Figure 1

Schematic representation of the mechanism underlying maternal immunization-induced immune protection in offspring. (A) Maternal immunization schedule providing a prime-boost DNA electrovaccination strategy in BALB/c female mice, which then mated with a transgenic BALB-neuT male. (B) Maternal DNA immunization leads to high levels of anti-neu IgG antibodies in mother’s sera being passed to offspring mainly through colostrum and milk. Maternally-derived IgG alone, or complexed with the EC portion of neu, bind the FcRn on the surface of the pup’s enterocytes. The antibody-receptor complex can be internalized and then released into the intestinal lumen. The IgG-neu ICs interact with DC through Fcγ receptors. The DC can then internalize the ICs and load neu peptides onto the MHC-I or MHC-II. The binding of CD8⁺ T cells that express specific TCR against p63-71 with the MHC-I-neu peptide complex on DCs leads to the expansion of this specific CD8⁺ T cell clone into the lymph nodes of offspring born from and fed by anti-neu vaccinated mothers, activating an effective cytotoxic T cell response. (C) List of pictures and related abbreviations.