Neonatal Vaccination : A Once in a Lifetime Opportunity
Demirjian, Alicia MD; Levy, Ofer MD

Introduction
Global eradication of smallpox and the forthcoming eradication of poliomyelitis are testimony to the power of immunization programs. It is both notable and sobering that over 2,000,000 newborns and infants under 6 months of age die each year due to infections.[1] Substantial morbidity and mortality among neonates and infants is related to vaccine-preventable infectious diseases. Immunization of pregnant mothers and passive transmission of antibodies to the fetus may be an effective way to protect the neonate, [2] but is limited by substantial safety and medico-legal concerns. Neonatal immunization is an approach that combines 2 major advantages: (a) birth is the most frequent and consistent point of healthcare contact, and (b ) it initiates early protective responses that shield the susceptible infant. Thus neonatal vaccines achieve relatively high population penetration.

Potential Challenges in Development of Neonatal Vaccines
Practical

The complexity of vaccine development is compounded when considering development of neonatal vaccines, as much biomedical research primarily focuses on adults, and less is known about the function of the neonatal immune system.[3]

Immunologic
The immune system of the newborn is functionally distinct and has been considered immunocompromised.[4] Impaired production of TH1-polarizing cytokines byneonatal antigen-presenting cells (APCs), in part reflecting high cytosolic concentrations of inhibitory cyclic adenosine monophosphate, and increased activity of inhibitory neonatal T regulatory cells limit adaptive immune responses at birth.[5] Neonatal responses are thus often TH2 -polarized. Moreover, maternal antibodies can inhibit responses to some antigens.[6] Certain antigens/adjuvant combinations, including BCG, engages the Toll-like receptor (TLR) system, can effectively activate T H 1 -polarizing neonatal adaptive immune responses in vitro and in vivo.[7]

Safety
Proof-of-concept for neonatal immunization exists in the form of vaccines, such as BCG and hepatitis B vaccine (HBV), given to millions of newborns and which have an excellent safety profile. Nevertheless, safety concerns are paramount in the development of any new biologic agent, particularly ones that may be given to an entire population at birth. The potential benefits of neonatalvaccination are thus tempered by parental and medical concerns about safety. Biopharmaceutical development of neonatal vaccines will have to proceed with caution , but also within a viable development pathway given the urgent unmet needs and potential of immunization at birth.[3,8]

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