New Horizons for Rabies Vaccines and Vaccination Strategies: Addressing 2030 Elimination Targets for Canine-mediated Rabies

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 36807

Special Issue Editors


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Guest Editor
Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Interests: epidemiology and evolution of emerging viral zoonoses

E-Mail Website
Guest Editor
Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Interests: evaluation of medical countermeasures for prevention and control of lyssavirus and poxvirus infections

Special Issue Information

Dear Colleagues,

This Special Issue of vaccines will be devoted to exploring new concepts in rabies vaccine development and utilization. Particular emphasis will be placed on innovations that hold the promise of improving vaccine uptake, efficacy, or effectiveness in ways to hasten progress toward the global health community’s stated goal of elimination of canine-mediated human rabies deaths by 2030. The implementation of effective canine vaccination programs has long been demonstrated to be the most cost-effective means of preventing human rabies deaths, but implementing successful programs in resource-limited countries has proven to be a chronic challenge. New ideas for optimizing and customizing canine vaccination campaign micro-plans, as well as further development of validated methods for enumerating canine population sizes and for efficiently vaccinating roaming dogs, are urgently needed. An additional tool of importance for diminishing the burden of rabies in the canine population would be a vaccine with the potential to engender enduring immunity—and possibly suppress reproduction — in canines. Improved, less-costly human pre- and post-exposure vaccines and biologics (or less protracted immunization schedules) would also contribute to decreasing the number of global human rabies deaths, as would the application of well-coordinated surveillance programs of bite-case management. Contributions to this Special Issue are anticipated to address a broad range of conceptual and practical issues related to how novel approaches to rabies vaccine development and utilization can promote the elimination of canine-mediated human rabies deaths across the globe.

Dr. Mary Reynolds
Dr. Victoria A. Olson
Guest Editors

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Keywords

  • Rabies
  • rabies vaccine
  • post-exposure prophylaxis
  • rabies elimination
  • oral rabies vaccine
  • free-roaming dog
  • integrated bite-case management
  • immuno-contraceptive rabies vaccine

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Published Papers (5 papers)

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Research

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15 pages, 1789 KiB  
Article
A Novel Integrated and Labile eHealth System for Monitoring Dog Rabies Vaccination Campaigns
by Andre Coetzer, Terence P. Scott, Khadija Noor, Lambert F. Gwenhure and Louis H. Nel
Vaccines 2019, 7(3), 108; https://doi.org/10.3390/vaccines7030108 - 9 Sep 2019
Cited by 14 | Viewed by 4324
Abstract
The elimination of canine rabies through the implementation of high coverage mass dog vaccination campaigns is a complex task, particularly in the resource-limited countries of the rabies endemic world. Here we demonstrated the feasibility of applying targeted rabies vaccination campaigns to deliver more [...] Read more.
The elimination of canine rabies through the implementation of high coverage mass dog vaccination campaigns is a complex task, particularly in the resource-limited countries of the rabies endemic world. Here we demonstrated the feasibility of applying targeted rabies vaccination campaigns to deliver more impactful intervention campaigns in resource-limited settings using evidence and lessons learnt from other diseases. With the use of strategic rabies intervention programs, we demonstrate the noteworthy reduction of rabies cases in two very different African settings. The strategic intervention was most significantly aided by the use of a custom-developed vaccination tracking device (the Global Alliance for Rabies Control (GARC) Data Logger) and an integrated rabies surveillance system (the Rabies Epidemiological Bulletin). Our first case study, an island-wide strategic dog vaccination on Tanzania’s Unguja island, reduced the incidence of rabies by 71% in the first 16 months of implementation. In the second case study, a similar approach was applied in the metropolitan capital city of Zimbabwe and the incidence of rabies declined by 13% during the first 13 months of implementation. The methodologies and results presented here suggest that, in resource-limited settings, an optimal approach towards the elimination of dog rabies would revolve around strategic interventions, subject to the use of appropriate planning, surveillance, and vaccination tools. Full article
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21 pages, 1342 KiB  
Article
Dog Ecology, Bite Incidence, and Disease Awareness: A Cross-Sectional Survey among a Rabies-Affected Community in the Democratic Republic of the Congo
by Céline Mbilo, Jean-Baptiste Kabongo, Pati Patient Pyana, Léon Nlonda, Raymond Williams Nzita, Bobo Luntadila, Badivé Badibanga, Jan Hattendorf and Jakob Zinsstag
Vaccines 2019, 7(3), 98; https://doi.org/10.3390/vaccines7030098 - 26 Aug 2019
Cited by 19 | Viewed by 6403
Abstract
Despite the existence of safe and efficacious human and animal rabies vaccines, millions of people remain at risk of exposure to this deadly zoonotic disease through bites of infected dogs. Sub-Saharan African countries, such as the Democratic Republic of the Congo (DRC), bear [...] Read more.
Despite the existence of safe and efficacious human and animal rabies vaccines, millions of people remain at risk of exposure to this deadly zoonotic disease through bites of infected dogs. Sub-Saharan African countries, such as the Democratic Republic of the Congo (DRC), bear the highest per capita death rates from rabies where dog vaccination and availability of lifesaving post-exposure prophylaxis (PEP) is scarce. Mass dog vaccination is the most cost-effective and sustainable approach to prevent human rabies deaths. We conducted a cross-sectional household survey in a rabies-affected community in Matadi, DRC, to estimate the size of the owned dog population and dog bite incidence and assess knowledge and practices regarding rabies, as preparation for future mass dog vaccination campaigns. Our study revealed that the owned dog population in Matadi was almost ten times larger than assumed by local veterinary officials, with a large proportion of free-roaming unvaccinated dogs. The annual dog bite incidence of 5.2 per 1000 person years was high, whereas community rabies knowledge was low resulting in poor practices. Given these findings, human rabies deaths are likely to occur in this community. Lack of disease awareness could negatively affect participation in future mass dog vaccination campaigns. A public sensitization campaign is needed to promote appropriate rabies prevention (washing bite wounds and PEP) and control (dog vaccination) measures in this community. Full article
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13 pages, 1375 KiB  
Article
Inactivated Rabies Virus-Vectored Immunocontraceptive Vaccine in a Thermo-Responsive Hydrogel Induces High and Persistent Antibodies against Rabies, but Insufficient Antibodies against Gonadotropin-Releasing Hormone for Contraception
by Xianfu Wu, Yong Yang, Chantal Kling, Laurie Seigler, Nadia F. Gallardo-Romero, Brock E. Martin, Todd G. Smith and Victoria A. Olson
Vaccines 2019, 7(3), 73; https://doi.org/10.3390/vaccines7030073 - 25 Jul 2019
Cited by 6 | Viewed by 4450
Abstract
Rabies is preventable through vaccination, but the need to mount annual canine vaccination campaigns presents major challenges in rabies control and prevention. The development of a rabies vaccine that ensures lifelong immunity and animal population management in one dose could be extremely advantageous. [...] Read more.
Rabies is preventable through vaccination, but the need to mount annual canine vaccination campaigns presents major challenges in rabies control and prevention. The development of a rabies vaccine that ensures lifelong immunity and animal population management in one dose could be extremely advantageous. A nonsurgical alternative to spay/neuter is a high priority for animal welfare, but irreversible infertility in one dose has not been achieved. Towards this goal, we developed a rabies virus-vectored immunocontraceptive vaccine ERA-2GnRH, which protected against rabies virus challenge and induced >80% infertility in mice after three doses in a live, liquid-vaccine formulation (Wu et al., 2014). To improve safety and use, we formulated an inactivated vaccine in a thermo-responsive chitosan hydrogel for one-dose delivery and studied the immune responses in mice. The hydrogel did not cause any injection site reactions, and the killed ERA-2GnRH vaccine induced high and persistent rabies virus neutralizing antibodies (rVNA) in mice. The rVNA in the hydrogel group reached an average of 327.40 IU/mL, more than 200 times higher than the liquid vaccine alone. The Gonadotropin-releasing hormone (GnRH) antibodies were also present and lasted longer in the hydrogel group, but did not prevent fertility in mice, reflecting a possible threshold level of GnRH antibodies for contraception. In conclusion, the hydrogel facilitated a high and long-lasting immunity, and ERA-2GnRH is a promising dual vaccine candidate. Future studies will focus on rabies protection in target species and improving the anti-GnRH response. Full article
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Review

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15 pages, 819 KiB  
Review
The Cellular Immune Response to Rabies Vaccination: A Systematic Review
by Lisanne A. Overduin, Jacques J.M. van Dongen and Leonardus G. Visser
Vaccines 2019, 7(3), 110; https://doi.org/10.3390/vaccines7030110 - 11 Sep 2019
Cited by 25 | Viewed by 9146
Abstract
The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on [...] Read more.
The effectiveness of rabies vaccines is conventionally determined by serological testing. In addition to this assessment of humoral immunity, cellular immunity could help assess effectiveness and protection through a broad range of parameters. Therefore, this study aimed to systematically review all literature on the kinetics and composition of the cellular immune response to rabies vaccination in humans. A total of 1360 studies were identified in an extensive literature search. Twenty studies were selected for inclusion. In a primary response, plasma cells are detectable from day 7 to day 14, peaking at day 10. Memory B-cells appear from day 10 up to at least day 28. After revaccination, natural killer (NK) cells are the first detectable cellular parameters. Further research is required to assess cellular parameters in relation to long-term (serological) immunity. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42019134416. Full article
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11 pages, 225 KiB  
Review
New Rabies Vaccines for Use in Humans
by Hildegund C. J. Ertl
Vaccines 2019, 7(2), 54; https://doi.org/10.3390/vaccines7020054 - 20 Jun 2019
Cited by 32 | Viewed by 11701
Abstract
Although vaccines are available, rabies still claims more than 55,000 human lives each year. In most cases, rabies vaccines are given to humans after their exposure to a rabid animal; pre-exposure vaccination is largely reserved for humans at high risk for contacts with [...] Read more.
Although vaccines are available, rabies still claims more than 55,000 human lives each year. In most cases, rabies vaccines are given to humans after their exposure to a rabid animal; pre-exposure vaccination is largely reserved for humans at high risk for contacts with the virus. Most cases of human rabies are transmitted by dogs. Dog rabies control by mass canine vaccination campaigns combined with intensive surveillance programs has led to a decline of human rabies in many countries but has been unsuccessful in others. Animal vaccination programs are also not suited to control human rabies caused by bat transmission, which is common in some Central American countries. Alternatively, or in addition, more widespread pre-exposure vaccination, especially in highly endemic remote areas, could be implemented. With the multiple dose regimens of current vaccines, pre-exposure vaccination is not cost effective for most countries and this warrants the development of new rabies vaccines, which are as safe as current vaccines, but achieve protective immunity after a single dose, and most importantly, are less costly. This chapter discusses novel rabies vaccines that are in late stage pre-clinical testing or have undergone clinical testing and their potential for replacing current vaccines. Full article
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