Improved vaccines through targeted manipulation of the body's immunological risk‐assessment?

Abstract

Recent advances have highlighted the outstanding role of the innate immune system for instructing adaptive immunity. Translating this knowledge into successful immunotherapies like vaccines, however, has proven to be a difficult task. This essay is based on the hypothesis that immune responses are tightly scaled to the infectious threat posed by a given microbial stimulus. A meticulous immunological risk‐assessment process is therefore instrumental for eliciting well‐balanced responses and maintaining immune homeostasis. The immune system makes fine distinctions, for example, between live and dead bacteria, or pathogenic and non‐pathogenic microorganisms. Here, I discuss recent evidence for some of the mechanisms underlying these distinctions and speculate on strategies for therapeutically targeting the immunological risk‐assessment machinery.

A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection

“…Studies on Prevnar-13 and during the development of Synflorix showed that ST3 is an especially challenging pneumococcal serotype to achieve high titers and memory even when conjugates of the large purified polysaccharide are injected (Poolman et al, 2009; Gruber et al, 2012; Prymula and Schuerman, 2014). Rather than using larger antigens, formulation effects like antigen loading, carrier protein and adjuvant adjustment to mobilize protective T cell and subsequent B cell memory responses may be required to increase the immunogenicity of semi-synthetic glycoconjugate vaccines (Snippe et al, 1983; Sander, 2012). Having a protective synthetic oligosaccharide lead antigen in hand will allow in-depth studies for hapten and formulation optimization.…”

“…The formulation including the employed adjuvants of the semi-synthetic vaccine needs further refinement to achieve long-lived immune memory. Activation of innate immune responses capable of instructing robust adaptive immunity may be crucial in this regard (Blander and Sander, 2012; Sander, 2012). …”

Strategies for Enhancement of Live-Attenuated Salmonella-Based Carrier Vaccine Immunogenicity

“…The mechanisms controlling the level of immune response against a given bacterial organism depend on overlapping and complementary detection strategies capable of discriminating between non-pathogenic and pathogenic organisms to mount either a tolerogenic non-inflammatory response or to trigger more robust adaptive immunity, respectively. Indeed, a theory describing a series of immune checkpoints for scaling the threat of a microbial infringement has recently been advanced [47,48], for which some formal evidence in support of specific aspects of the theory is now accumulating.…”