Self-disseminating vaccines for emerging infectious diseases

Murphy, Aisling A.; Redwood, Alec; Jarvis, Michael A.

doi:10.1586/14760584.2016.1106942

Cited by 46 publications

(58 citation statements)

References 62 publications

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“…The potential for a transmissible or self-disseminating vaccine to facilitate efforts to control and eradicate infectious disease has long been appreciated [42], but the oral polio vaccine and vaccines designed for wildlife remain the only welldocumented examples [1,6,[8][9][10][11][12]. Much of the reticence surrounding the development of transmissible vaccines stems from the justifiable concern that the potential for evolutionary reversion to wild-type virulence outweighs their potential benefits.…”

Section: Resultsmentioning

confidence: 99%

“…Instead, the real power of transmissible vaccines likely lies in their ability to improve vaccine coverage in populations of livestock and wildlife where direct vaccination of a significant proportion of the population is excessively costly or even impossible in many cases. Although transmissible vaccines have not yet been used in this capacity on a large scale, a recombinant transmissible vaccine has been developed to protect wild rabbit populations against myxomatosis [9] and to interrupt the transmission of Sin Nombre hantavirus in reservoir populations of deer mice [6]. Similar approaches could be used to develop transmissible vaccines against invasive wildlife diseases, such as West Nile virus [27], to protect threatened wildlife populations from infectious disease [28] or to eliminate diseases like rabies from wild reservoir populations.…”

Section: Discussionmentioning

confidence: 99%

“…Recent advances in molecular biology suggest that the centuries-old method of individual-based vaccine delivery could be on the cusp of a major revolution. Specifically, genetic engineering brings to life the possibility of a transmissible or 'self-disseminating' vaccine [6,7]. Rather than directly vaccinating every individual within a population, a transmissible vaccine would allow large swaths of the population to be vaccinated effortlessly by releasing an infectious agent genetically engineered to be benign yet infectious.…”

Section: Introductionmentioning

confidence: 99%

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Eradicating infectious disease using weakly transmissible vaccines

et al. 2016

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eradicating infectious disease using weakly transmissible vaccines

et al. 2016

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“…In most cases, the choice of a vector may be based on considerations that lie outside model results, and the model results will then inform the possibilities and avenues for success. Consider cytomegalovirus (CMV), a vector currently being used in the development of transmissible vaccines targeting Ebola and Lassa fever (Marzi et al, ; Murphy et al, ; Tsuda et al, , ). CMV appears promising because of its high level of species specificity, and ability to readily reinfect previously infected hosts (Murphy et al, ), a property shown to be critically important here, and in a previous study (Basinski et al, ).…”

Section: Discussionmentioning

confidence: 99%

Evolution and containment of transmissible recombinant vector vaccines

Nuismer

Basinski

Bull

2019

Evolutionary Applications

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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.

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“…In some cases where culling has been employed and studied, however, it has been shown to have potentially counter-intuitive impacts, potentially increasing the prevalence of the target pathogen (Streicker et al 2012; Amman et al 2014). A second alternative to conventional vaccination relies on the use of transmissible vaccines capable of transmitting infectiously within the target population (Murphy et al 2016; Nuismer et al 2016; Bull et al 2018). Transmissible vaccines have been show to substantially improve the likelihood of eliminating infectious disease in theoretical studies, but have been explored empirically in only a small number of cases (Bárcena et al 2000; Angulo and Barcena 2007; Murphy et al 2016; Bull et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Bayesian estimation of Lassa virus epidemiological parameters: implications for spillover prevention using wildlife vaccination

Nuismer

Remien

Basinski

et al. 2019

Preprint

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32Lassa virus is a significant burden on human health throughout its endemic region in 33 West Africa, with most human infections the result of spillover from the primary rodent 34 reservoir of the virus, the natal multimammate mouse, M. natalensis. Here we develop a 35 Bayesian methodology for estimating epidemiological parameters of Lassa virus within its 36 rodent reservoir and for generating probabilistic predictions for the efficacy of rodent 37 vaccination programs. Our approach uses Approximate Bayesian Computation (ABC) to 38 integrate mechanistic mathematical models, remotely-sensed precipitation data, and Lassa 39 virus surveillance data from rodent populations. Using simulated data, we show that our 40 method accurately estimates key model parameters, even when surveillance data are available 41 from only a relatively small number of points in space and time. Applying our method to 42 previously published data from two villages in Guinea estimates the time-averaged of Lassa 0 43 virus to be 1.658 and 1.453 for rodent populations in the villages of Bantou and Tanganya, 44 respectively. Using the posterior distribution for model parameters derived from these 45 Guinean populations, we evaluate the likely efficacy of vaccination programs relying on 46 distribution of vaccine-laced baits. Our results demonstrate that effective and durable 47 reductions in the risk of Lassa virus spillover into the human population will require repeated 48 distribution of large quantities of vaccine. 49 3 50 Author Summary 51 Lassa virus is a chronic source of illness throughout West Africa, and is considered to be a threat 52 for widespread emergence. Because most human infections result from contact with infected 53 rodents, interventions that reduce the number of rodents infected with Lassa virus represent 54 promising opportunities for reducing the public health burden of this disease. Evaluating how 55 well alternative interventions are likely to perform is complicated by our relatively poor 56 understanding of viral epidemiology within the reservoir population. Here we develop a novel 57 statistical approach that couples mathematical models and viral surveillance data from rodent 58 populations to robustly estimate key epidemiological parameters. Applying our method to 59 existing data from Guinea yields well-resolved parameter estimates and allows us to simulate a 60 variety of rodent vaccination programs. Together, our results demonstrate that rodent 61 vaccination alone is unlikely to be an effective tool for reducing that public health burden of 62 Lassa fever within West Africa. 63 65 Lassa virus is a zoonotic pathogen endemic to West Africa where it poses a significant 66 burden on human health (Buckley et al. 1970). Although only a relatively small proportion of 67 human cases result in severe symptoms and mortality, human infection is common, with 8-52% 68 of the human population within Sierra Leone seropositive (McCormick et al. 1987; Bausch et al. 69 2001; Dan-Nwafor et al. 2019), indicative of past...

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Self-disseminating vaccines for emerging infectious diseases

Cited by 46 publications

References 62 publications

Eradicating infectious disease using weakly transmissible vaccines

Eradicating infectious disease using weakly transmissible vaccines

Evolution and containment of transmissible recombinant vector vaccines

Bayesian estimation of Lassa virus epidemiological parameters: implications for spillover prevention using wildlife vaccination

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