Pandemics unveil major shortcoming in contemporary vaccine design: Too little, too late.

Vaccines Summit 2021

September 20-22

Current ‘progress’ in the vaccine field is largely based on new technologies such as those involved in novel manufacturing processes or in big data mining (-omics) enabling molecular analysis of immunorelevant genes and immune signalling pathways. However, much less progress has been made in our fundamental understanding of host-pathogen interactions and immune subversive mechanisms which pathogenic agents have evolved to escape natural mechanisms of host immune defence. As a result, selection of vaccinal antigens still largely relies on naturally induced immune responses that correlate with recovery from acute disease caused by specific pathogens. The immune responses these antigens induce are restricted by antigenic variability of the pathogen and/ or the immuno-genetic background of the host. Immune responses induced by contemporary vaccines are, therefore, prone to immune escape. Natural selection of immune escape variants is even more likely to occur when individuals exerting suboptimal immune pressure have a high chance of becoming exposed to circulating virus. Provided widespread immune selection pressure, these immune escape variants will even be able to adapt to the rising immune status of the vaccinated population. This already explains why classical vaccines fail to prevent variants from arising and further evolving when mass vaccination campaigns are conducted in populations that are continuously exposed to the circulating virus, a situation which typically occurs during a pandemic. Under these conditions, the effect of these vaccines is simply ‘too little’ and comes ‘too late’ to prevent evolving variants from circumventing vaccine-elicited immunity.

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