Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.

Viral vaccines have had remarkable positive impacts on human health as well as the health of domestic animal populations. Despite impressive vaccine successes, however, many infectious diseases cannot yet be efficiently controlled or eradicated through vaccination, often because it is impossible to vaccinate a sufficient proportion of the population. Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery may be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a live, transmissible vaccine. Unfortunately, releasing a highly transmissible vaccine poses substantial evolutionary risks, including reversion to high virulence as has been documented for the oral polio vaccine. An alternative, and far safer approach, is to rely on genetically engineered and weakly transmissible vaccines that have reduced scope for evolutionary reversion. Here, we use mathematical models to evaluate the potential efficacy of such weakly transmissible vaccines. Our results demonstrate that vaccines with even a modest ability to transmit can significantly lower the incidence of infectious disease and facilitate eradication efforts. Consequently, weakly transmissible vaccines could provide an important tool for controlling infectious disease in wild and domestic animal populations and for reducing the risks of emerging infectious disease in humans.

As the density of human and domestic animal populations increases, the threat of localized epidemics and global pandemics grows. Although effective vaccines have been developed for a number of threatening pathogens, manufacturing and disseminating vaccines in the face of a rapidly spreading epidemic or pandemic remains a formidable challenge. One potentially powerful solution to this problem is the use of transmissible vaccines. Transmissible vaccines are capable of spreading from one individual to another and are currently being developed for a range of infectious diseases. Here we develop and analyze mathematical models that allow us to quantify the benefits of vaccine transmission in the face of an imminent or ongoing epidemic. Our results demonstrate that even a small amount of vaccine transmission can greatly increase the rate at which a naïve host population can be protected against an anticipated epidemic and substantially reduce the size of unanticipated epidemics if vaccination is initiated shortly after pathogen detection. In addition, our results identify key biological properties and implementation practices that maximize the impact of vaccine transmission on infectious disease.

BackgroundWe propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus ‘wars’ in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus.ResultsNumerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved. The protective system was implemented and tested using E. coli, bacteriophage M13 and a phagemid vector mobilized by M13 to block infection by the lethal phage T5. Engineering of M13 profoundly improved its dynamical properties for facilitating spread of the gene therapy vector. However, the gene therapy vector converts the host cell to resist T5 too slowly for protection on a time scale appropriate for T5.ConclusionsOverall, there is a reasonable marriage between the mathematical model and the empirical system, suggesting that such models can be useful guides to the design of such systems even before the models incorporate most of the relevant biological details.Electronic supplementary materialThe online version of this article (doi:10.1186/s13036-016-0033-4) contains supplementary material, which is available to authorized users.