Vaccination strategies to enhance immunity in neonates

Abstract

Neonates are particularly susceptible to infection. This vulnerability occurs despite their responsiveness to most vaccines. However, current vaccines do not target the pathogens responsible for most of the severe neonatal infections, and the time it takes to induce protective pathogen-specific immunity after vaccination limits protection in the first days to weeks of life. Alternative strategies include using vaccines to broadly stimulate neonatal immunity in a pathogen-agnostic fashion or vaccinating women during pregnancy to induce protective antibodies that are vertically transferred to offspring within their window of vulnerability. Protection may be further improved by integrating these approaches, namely vaccinating the neonate under the cover of vertically transferred maternal immunity. The rationale for and knowledge gaps related to each of these alternatives are discussed.

Fig. 1.. Current maternal and neonatal vaccines do not cover most pathogens associated with severe infection in early life.

Relative proportion of each pathogen, represented by the size of each segment, identified in recent studies of suspected sepsis in early life (–9). The top pathogens from each study are shown, covering >90% of cases in which a pathogen was identified. Age range (in days) and number of neonates are shown for each study.

Fig. 2.. Tempo of immunity provided by vaccination at birth compared with vaccination during pregnancy in relation to the neonatal window of infection susceptibility.

(A) Antibody levels primed by neonatal vaccination increase with delayed tempo, which offers suboptimal protection during the early life window of susceptibility. (B) Maternal immunization provides high levels of pathogen-specific antibodies at birth and is an effective strategy for narrowing the window of susceptibility to specific pathogens. (C) Combining maternal vaccination with pathogen-agnostic and pathogen-specific benefits of neonatal vaccination may contribute equally to optimal neonatal immune fitness and efficiently close the early life window of susceptibility.