Evolution and containment of transmissible recombinant vector vaccines

Abstract

Transmissible vaccines offer a revolutionary approach for controlling infectious disease and may provide one of the few feasible methods for eliminating pathogens from inaccessible wildlife populations. Current efforts to develop transmissible vaccines use recombinant vector technology whereby pathogen antigens are engineered to be expressed from innocuous infectious viral vectors. The resulting vaccines can transmit from host to host, amplifying the number of vaccine‐protected individuals beyond those initially vaccinated directly through parenteral inoculation. One main engineering challenge is the potential for natural selection to favor vaccine mutants that eliminate or reduce expression of antigenic inserts, resulting in immunogenic decay of the vaccine over time. Here, we study a mathematical model of vector mutation whereby continuous elimination of the antigenic insert results in reversion of the vaccine back into the insert‐free vector. We use this model to quantify the maximum allowable rate of reversion that can be tolerated for a transmissible vaccine to maintain a critical threshold level of immunogenicity against a target pathogen. Our results demonstrate that even for transmissible vaccines where reversion is frequent, performance will often substantially exceed that of conventional, directly administered vaccines. Further, our results demonstrate the feasibility of designing transmissible vaccines that yield desired levels of immunogenicity, yet degrade at a rate sufficient for persistence of the recombinant vaccine within the environment to be minimized.

New insights on possible vaccine development against SARS-CoV-2

“…Similarly, a recent study suggested that the development of oral live attenuated virus vaccine could be a potential target to diminish the lung infections triggered by SARS-CoV-2, due to its initial infection in guts which resultingly boosted up the mucosa that associated with immune system during the early immune response against COVID-19 [ 68 ]. Another study also reported that the live attenuated virus vaccine could easily be administrated and serve as a community spread to rapidly develop herd immunity against the pathogens of COVID-19 [ 69 ].…”

Suppressing evolution in genetically engineered systems through repeated supplementation

“…Transmissible vaccines reduce the level of direct vaccination necessary to achieve pathogen eradication (Nuismer, Basinski, & Bull, 2019). These novel vaccine designs offer new opportunities for eliminating the threat of many zoonotic pathogens by targeting them in their wild animal reservoirs before they disseminate into human populations.…”

“…Calculations of herd immunity determine the level of supplementation of a nonreplicating vaccine necessary to keep a pathogen from invading. Previous work on transmissible vaccines has shown that the level of direct vaccination necessary to protect a population can be greatly reduced using even weakly transmissible vaccines, but they are subject to evolutionary decay (Basinski et al, 2018;Nuismer et al, 2019). Here, we expand on these models to ask whether the effectiveness of a transmissible vaccine subject to (4) As with previous models of transmissible vaccine evolution, we assume that the mutated/degraded vaccine strain is initially absent from the population.…”

“…However, the transgene is expected to experience evolutionary decay unless it provides a benefit to the vector (Bull, Nuismer, & Antia, 2019). Even if the “intrinsic” cost of carrying an antigenic transgene can be completely avoided, mutations that reduce immune overlap between the vaccine and the pathogen will still be favored, reducing the effectiveness of a transmissible vaccine (Basinski et al., 2018; Bull, Smithson, & Nuismer, 2018; Evans et al, 1985; Nuismer et al., 2019).…”

Basics for Improved Use of Phages for Therapy

“…In addition, when serially propagated, particularly in the wild, recombinant phages and other viruses undergo spontaneous genome re-engineering by mutation/selection [ 17 , 18 ]. The apparent reason is distortion of the original engineering by an inserted gene.…”