Genesis of Antibiotic Resistance (AR) LXX: Mechanism(s) of heterogeneity due to Fickle vaccine campaign prodded selection of epitope pool confer vaccine resistance consequent AR Pandemic (ARP) ‐ An Episodic selection pressure provoked Bottle neck event driven genetic drift in gene flow

Abstract

The precise evolutionary mechanisms underlying vaccination campaign followed by serotype surveillance, serotype (Antigenic) multiplicity, serotype(Antigenic) variation, serotype conversion, serotype replacement, serotype diversity, and ultimate vaccine break potential and their role in vaccine resistance is not well understood at present. It is known that vaccination does not protect a host against all known serotypes of the target pathogen while it is known that all hosts do not generate an identical immune response (PMCID: PMC6304978 / PMID: 30559199; PMID: 28356449 / PMCID: PMC5378080 ). For example, Yersinia ruckeri, the causative agent of enteric red mouth disease, was known to have two biotypes, a motile type with a flagellum [biotype 1(Bt1)] and a non-motile type that lacks a flagellum (Bt2) (J Fish Dis. 1989;12:357–365). An outbreak in vaccinated populations implied that the vaccine resistance could have been caused by Bt2 (PMID: 18236630). The flagellin, a defining difference between Bt1 and Bt2, (PMID: 26719024), was attributed to conferring vaccine resistance against Yersinia ruckeri. On the contrary, it was shown that bacterial isolates differ in their ability to cause disease in vaccinated hosts, regardless of the presence of a flagellum. Here we present a plausible evolutionary mechanism(s) for the evolution of novel serotypes, antigenic loss, antigenic drift and life-history modifications, pathogen adaptation which will eventually undermine existing and next-generation vaccines directed at a multitude of epitopes of a target pathogen. It is suggested that subsequent to the vaccination campaign, the pathogenic potential of the target epitope(s) of a given pathogen is subjected to natural selection process altering the pattern of distribution of antigenic variants by either one or more process: directional selection favoring the antigenic variants at the extreme either genotype of dominant or recessive traits, disruptive selection favoring the antigenic variants at both ends dominant/recessive traits, and stabilizing selection favoring the elimination of extreme variants either dominant or recessive from the pool of epitopes and preserving the intermediate variants mounting the resistance to any given type of vaccination protocol (p497 – 498: ISBN: 978 013 518 8743. Pearson, NY .2020). Persisters (PMID: 20528688; PMID: 28529326; PMID: 29857815; PMID: 30414937; PMID: 30082460; PMID: 31036343) subjected to vaccine exposure and evolutionary selection pressure would acquire adaptive evolution endowed with unpredictable fluctuation of antigenic variation from one generation to next generation (Genetic Drift), forming a totally new genotype and phenotype variation (Founder effect) with altered “gene flow” impeding the prophylactic efficacy of vaccines. Taken together, the aforesaid mechanisms suggested to play a pivotal role in the processes of hyper mutation-induced affinity maturation of epitope(s) pool of persisters conferring vaccine resistance.