Immunization of newborns with bacterial conjugate vaccines

Ontogeny of early life immunity

“…For example, a birth dose of alum-adjuvanted pneumococcal conjugate vaccine resulted in altered TLR-mediated cytokine responses at 9 months of age [31]. Therefore, future development of novel age-specific vaccine formulations and delivery systems is likely warranted [108]. Given that ~11% of the global population is born preterm [109], the high burden of preterm infection [110], and that preterms demonstrate distinct immunity [111] which is incompletely characterized, there is a particular need to accurately model preterm immune responses to adjuvants and vaccines.…”

TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

“…Although the majority of global immunization schedules are focused on the pediatric age group, development of early life vaccines has been hampered by this distinct immunity and an ad hoc approach in developing vaccines for adults prior to infant trials (2). By comparison to initiation of immunization in infancy, accelerated neonatal immunization strategies may be highly advantageous (3,4) because (a) newborn vaccines achieve relatively high population penetration, as birth is the most reliable point of health care contact worldwide (5); (b) there is high risk of severe infection after very early life colonization; and (c) reduced vaccine responses can occur after bacterial colonization (6,7). Adjuvantation is a key tool to enhance vaccine-induced immunity.…”

“…However, PCV-induced protection may not be fully achieved until completion of the recommended vaccination schedule (12-18 months of life) (20), and the inclusion of alum, though safe and effective, appears to be Th2 polarizing (24) and results in a formulation that requires multiple doses prior to achieving protective Ab titers. In this context, we have selected PCV13, which protects against Streptococcus pneumoniae, as a model vaccine to adjuvant, because (a) PCV13 is a well-studied vaccine with known correlates of protection, which allows clear and unambiguous evaluation of our adjuvantation strategy; (b) current PCVs can prevent severe disease in older children and offer newborns some indirect herd protection, but newborns are not directly protected; (c) pneumococcal diseases strikes in early life, particularly in resource-poor countries, such as Papua New Guinea, making a vaccine that provides rapid protection in early life desirable (3,4); and (d) although studies of PCV7 immunization, with a 3-dose schedule starting at birth, induced protective serum Ab concentrations in human infants as early as 18 weeks (4.5 months), neonatal hyporesponsiveness was noted for several vaccine serotypes, as compared with infants starting a 3-dose schedule of PCV7 at 2 months of life (24,25).…”

Age-Specific Adjuvant Synergy: Dual TLR7/8 and Mincle Activation of Human Newborn Dendritic Cells Enables Th1 Polarization

“…The synthetic MPLA analog glucopyranosyl lipid adjuvant (GLA) is another TLR4 agonist that has shown promise in vitro and in vivo, including in human clinical trials (11,12). Importantly, adjuvants can have age-specific immune-enhancing effects, and adjuvants that induce a strong Th1 response in adults may induce Th2-biased immune responses early in life (8,13,14).…”