Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as Bacillus Calmette Guérin (BCG) and Hepatitis B vaccine (HBV), do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination.

Neonates and infants suffer a high frequency and severity of microbial infection resulting in millions of deaths worldwide. The same immune deficiencies that render newborns susceptible to infection also reduce their memory responses to most antigens, thereby potentially frustrating efforts to protect this high-risk population. As birth is the most reliable point of healthcare contact worldwide and effective vaccination at birth would provide early protection for newborns and infants, expanding and improving the available means of neonatal vaccination is a global health priority. Newborns have impaired immune responses due to a range of deficiencies in both adaptive immunity and innate immunity , as well as the potentially suppressive effects of maternally-derived antibodies (MatAb). Newborns exhibit increased activity of suppressive T regulatory cells