Abstract
Traditional vaccine development against infectious diseases has been guided by the overarching aim to generate efficacious vaccines normally indicated by an antibody and/or cellular response that correlates with protection. However, this approach has been shown to be only a partially effective measure, since vaccine- and pathogen-specific immunity may not perfectly overlap. Thus, some vaccine development strategies, normally focused on targeted generation of both antigen specific antibody and T cell responses, resulting in a long-lived heterogenous and stable pool of memory lymphocytes, may benefit from better mimicking the immune response of a natural infection. However, challenges to achieving this goal remain unattended, due to gaps in our understanding of human immunity and full elucidation of infectious pathogenesis. In this review, we describe recent advances in the development of effective vaccines, focusing on how understanding the differences in the immunizing and non-immunizing immune responses to natural infections and corresponding shifts in immune ontogeny are crucial to inform the next generation of infectious disease vaccines.
Highlights
Apart from clean drinking water and sanitation, vaccination is one of the most effective medical interventions to avert infectious diseases [1, 2]
Vaccines are one of the most cost-effective and effective interventions to address the global burden of pediatric infectious diseases and the implementation of early life immunizations has reduced deaths in neonates and children across the world [4]
Infants are capable of inducing adaptive immune responses after pathogen exposure
Summary
Apart from clean drinking water and sanitation, vaccination is one of the most effective medical interventions to avert infectious diseases [1, 2]. Despite the great successes of past revolutions in vaccinology, current vaccine technologies may still provide suboptimal protection in vulnerable populations, such as infants [1] and the elderly [3]. Inactivated, live attenuated, subunit, Lessons From Natural Immunity recombinant, polysaccharide and conjugate vaccines-which all induce humoral and cell mediated immunity-have been used to protect against different viral and bacterial infections. We discuss three examples, tuberculosis, pertussis and influenza, in which lessons can be learnt from our current understanding of natural pathogen-specific immunity which can better guide (Box 1) novel vaccination strategies to elicit targeted and effective immune activation in neonates and infants, with possible applicability in vulnerable elders and those with immunocompromised status. A number of important caveats need to be addressed, including: i) whether induction of beneficial unnatural immunity can be incorporated into the designing of broad spectrum generation vaccines [reviewed in [15, 16]], ii) whether these strategies can induce innate immunity and vaccine efficacy in early and later life [reviewed in [6, 11] and [17]], and iii) how can a growing body of vaccine adjuvants, in combination with formulation science of vaccine delivery, such as lipo-nanoparticle based mRNA technologies [3], be used to open up a new toolbox for vaccinologists [reviewed in [12] and [13]]
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