Precision adjuvants for pediatric vaccines

Abstract

Elucidating optimal vaccine adjuvants for harnessing age-specific immune pathways to enhance magnitude, breadth, and durability of immunogenicity remains a key gap area in pediatric vaccine design. A better understanding of age-specific adjuvants will inform precision discovery and development of safe and effective vaccines for protecting children from preventable infectious diseases.

Fig. 1.. Rational development of adjuvants for pediatric vaccines.

(A) Human newborns are equipped with all immune organs and immune cells, but functional maturation occurs primarily postbirth in a dynamic manner following a regulated trajectory. The overall ontogenetic trajectory is similar independent of gestational age (GA) at birth, although preterm infants can present with unique immune features, such as reduced passively transferred maternal antibodies. The dynamic nature of the infant immune system combined with the establishment of the normal host microbiota, sudden exposure to a wealth of microorganisms, and decline of transferred maternal immunity translate into a period of heightened susceptibility to infectious diseases in early life, especially during the first 3 months, that gradually decreases with age. (B to D) The left illustrations show the APC–T cell–B cell interactions, and the right plots highlight the differences in antibody responses dependent on adjuvant usage and adjuvant type. Ag, antigen; MHC, major histocompatibility complex; TCR, T cell receptor. (B) Protein or subunit vaccines administered without adjuvants poorly activate APCs, resulting in suboptimal T cell help and low antibody responses by B cells. (C) Among adjuvanted pediatric vaccines, alum-based adjuvants are most commonly used. However, alum-based adjuvants might be limited in the induction of long-term T and B cell memory in neonates and infants as they are less effective in activating APCs and promote T_H2 responses. (D) Precision adjuvants that are rationally designed and selected to enhance APC function will increase vaccine immunogenicity, enhancing CD4 cell responses and long-lived antibody responses. As an example, a precision adjuvant able to bind to an extracellular intracellular PRR is shown.