Rabies Vaccines and Immunoglobulins

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Veterinary Vaccines".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 18522

Special Issue Editors


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Guest Editor
School of Veterinary Medicine, Ross University, Basseterre, St Kitts, Saint Kitts and Nevis
Interests: rabies; dog population ecology; zoonoses; epidemiology

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Guest Editor
Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET-Fundación Pablo Cassará, Ciudad de Buenos Aires, Argentina
Interests: research and development on rabies vaccines

Special Issue Information

Dear Colleagues,

Rabies is a typically fatal but vaccine-preventable disease caused by infection with rabies virus (RABV) and other members of the Lyssavirus family. Rabies vaccines and immunoglobulins are essential for the prevention and control of the disease in human and animal populations. In this Special Issue, we invite submissions of original research or review articles to highlight the state of the art and future directions in the development of these biologics. Our scope encompasses use in humans or animals, for pre- or post-exposure prophylaxis or treatment. Topics of interest include (but are not limited to) safety, immunogenicity, and efficacy of current and next-generation rabies vaccines and immunoglobulins; delivery strategies for pre-exposure prophylaxis for domestic animal, wildlife or human populations; cost-effectiveness studies; thermostability; novel adjuvants; non-specific effects of vaccines; preclinical, clinical. or post-marketing studies of new products, regimens, or routes of administration; use of recombinant monoclonal antibodies for post-exposure prophylaxis or treatment.

Prof. Dr. Darryn Knobel
Dr. Carlos Palacios
Guest Editors

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Keywords

  • pre-exposure prophylaxis
  • post-exposure prophylaxis
  • treatment
  • safety
  • efficacy
  • immunogenicity
  • non-specific effects
  • vaccine delivery
  • adjuvants
  • monoclonal antibodies

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Published Papers (6 papers)

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11 pages, 2128 KiB  
Article
Efficiency Comparative Approach of Plant-Produced Monoclonal Antibodies against Rabies Virus Infection
by Boonlert Lumlertdacha, Bancha Mahong, Kaewta Rattanapisit, Christine Joy I. Bulaon, Thiravat Hemachudha and Waranyoo Phoolcharoen
Vaccines 2023, 11(8), 1377; https://doi.org/10.3390/vaccines11081377 - 17 Aug 2023
Cited by 1 | Viewed by 1818
Abstract
Rabies encephalitis is a fatal zoonotic viral disease caused by the neurotropic rabies virus. It remains a major public health concern as it causes almost 100% fatality and has no effective medication after the onset of the disease. However, this illness is preventable [...] Read more.
Rabies encephalitis is a fatal zoonotic viral disease caused by the neurotropic rabies virus. It remains a major public health concern as it causes almost 100% fatality and has no effective medication after the onset of the disease. However, this illness is preventable with the timely administration of effective post-exposure prophylaxis (PEP) consisting of the rabies vaccine and passive immune globulins (HRIG and ERIG). Recently, conventional PEP has been shown to have many limitations, resulting in little support for these expensive and heterologous globulins. Monoclonal antibody (mAb) production via recombinant technology in animal and human cell cultures, as well as a plant-based platform, was introduced to overcome the costly and high-tech constraints of former preparations. We used transient expression technology to produce two mAbs against the rabies virus in Nicotiana benthamiana and compared their viral neutralizing activity in vitro and in vivo. The expression levels of selective mAbs E559 and 62-71-3 in plants were estimated to be 17.3 mg/kg and 28.6 mg/kg in fresh weight, respectively. The plant-produced mAbs effectively neutralized the challenge virus CVS-11 strain in a cell-based RFFIT. In addition, the combination of these two mAbs in a cocktail protected hamsters from rabies virus infection more effectively than standard HRIG and ERIG. This study suggests that the plant-produced rabies antibody cocktail has promising potential as an alternative biological to polyclonal RIG in rabies PEP. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
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20 pages, 2164 KiB  
Article
Comparative Neutralization Activity of Commercial Rabies Immunoglobulin against Diverse Lyssaviruses
by Jessica Coertse, Natalie Viljoen, Jacqueline Weyer and Wanda Markotter
Vaccines 2023, 11(7), 1255; https://doi.org/10.3390/vaccines11071255 - 18 Jul 2023
Cited by 4 | Viewed by 2035
Abstract
Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin [...] Read more.
Novel lyssaviruses, the causative agents of rabies, continue to be described mostly due to increased surveillance in bat hosts. Biologicals for the prevention of rabies in humans have, however, remained largely unchanged for decades. This study aimed to determine if commercial rabies immunoglobulin (RIG) could neutralize diverse lyssaviruses. Two commercial preparations, of human or equine origin, were evaluated against a panel consisting of 13 lyssavirus species. Reduced neutralization was observed for the majority of lyssaviruses compared to rabies virus and was more evident for lyssaviruses outside of phylogroup I. Neutralization of more diverse lyssaviruses only occurred at very high doses, except for Ikoma lyssavirus, which could not be neutralized by the RIG evaluated in this study. The use of RIG is a crucial component of rabies post-exposure prophylaxis and the data generated here indicate that RIG, in its current form, will not protect against all lyssaviruses. In addition, higher doses of RIG may be required for neutralization as the genetic distance from vaccine strains increases. Given the limitations of current RIG preparations, alternative passive immunization options should be investigated. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
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16 pages, 2071 KiB  
Article
Effect of Phone Text Message Reminders on Compliance with Rabies Post-Exposure Prophylaxis following Dog Bites in Rural Kenya
by Veronicah M. Chuchu, Nyamai Mutono, Philet Bichanga, Philip M. Kitala, Daniel Ksee, Mathew Muturi, Athman Mwatondo, Carolyne Nasimiyu, Lawrence Akunga, Amine Amiche, Katie Hampson and Samuel M. Thumbi
Vaccines 2023, 11(6), 1112; https://doi.org/10.3390/vaccines11061112 - 18 Jun 2023
Cited by 6 | Viewed by 2243
Abstract
The prompt administration of post-exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. A delay in seeking the first dose of rabies PEP, or failure to complete the recommended dosage, may result in clinical rabies and death. [...] Read more.
The prompt administration of post-exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. A delay in seeking the first dose of rabies PEP, or failure to complete the recommended dosage, may result in clinical rabies and death. We assessed the efficacy of short message system (SMS) phone texts in improving the adherence to scheduled PEP doses among bite patients in rural eastern Kenya. We conducted a single-arm, before-after field trial that compared adherence among bite patients presenting at Makueni Referral Hospital between October and December 2018 (control) and between January and March 2019 (intervention). Data on their demographics, socio-economic status, circumstances surrounding the bite, and expenditures related to the bite were collected. A total of 186 bite patients were enrolled, with 82 (44%) in the intervention group, and 104 (56%) in the control group. The odds of PEP completion were three times (OR 3.37, 95% CI 1.28, 10.20) more likely among patients who received the SMS reminder, compared to the control. The intervention group had better compliance on the scheduled doses 2 to 5, with a mean deviation of 0.18 days compared to 0.79 days for the control group (p = 0.004). The main reasons for non-compliance included lack of funds (30%), and forgetfulness (23%) on days for follow-up treatment, among others. Nearly all (96%, n = 179) the bite patients incurred indirect transport costs, at an average of USD 4 (USD 0–45) per visit. This study suggests that the integration of SMS reminders into healthcare service delivery increases compliance with PEP, and may strengthen rabies control and elimination strategies. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
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9 pages, 245 KiB  
Article
Potency of Veterinary Rabies Vaccines Marketed in Sri Lanka
by Hasanthi Rathnadiwakara, Mangala Gunatilake, Alexandre Servat, Marine Wasniewski, Jean-Christophe Thibault and Florence Cliquet
Vaccines 2023, 11(5), 961; https://doi.org/10.3390/vaccines11050961 - 9 May 2023
Cited by 3 | Viewed by 2570
Abstract
Seven brands of veterinary rabies vaccines are commercially available in Sri Lanka, but there is no established procedure to test the potency of the vaccines at the local level, especially prior to their release. The aim of this study was to test the [...] Read more.
Seven brands of veterinary rabies vaccines are commercially available in Sri Lanka, but there is no established procedure to test the potency of the vaccines at the local level, especially prior to their release. The aim of this study was to test the potency of these vaccines using a mouse challenge test in collaboration with the EU/WOAH/WHO Reference Laboratory for Rabies, ANSES-Nancy, France. Based on the European Pharmacopoeia, the inactivated rabies vaccines complied with the mouse potency test if the estimated potency is ≥1.0 IU in the smallest prescribed dose. Among the eight tested vaccines, four single-dose preparations (Rabisin™, Raksharab™, Nobivac™ RL, and Nobivac™ Rabies) were compliant, with potencies of 12 IU/dose, 7.2 IU/dose, 4.4 IU/dose, and 3.4 IU/dose, respectively. Three of the single-dose preparations (Canvac™ R, Defensor™ 3, and Rabies killed vaccine) were not compliant, with potency values <1.0 IU/dose. One multidose preparation (Raksharab™ multidose) had a potency of 1.3 IU/dose, even though the test was not validated. Based on these results, it appears that some rabies vaccine batches that are currently available in the local market do not comply with the mouse potency test. Testing the vaccines’ potency before registration and release to the market appears to be an important step to allow good immunization to animals during pre-exposure vaccination programs. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
11 pages, 1144 KiB  
Article
Efficacy of Oral Rabies Vaccine Baits Containing SPBN GASGAS in Domestic Dogs According to International Standards
by Katharina Bobe, Steffen Ortmann, Christian Kaiser, David Perez-Bravo, Jörn Gethmann, Jeannette Kliemt, Sophia Körner, Tobias Theuß, Thomas Lindner, Conrad Freuling, Thomas Müller and Ad Vos
Vaccines 2023, 11(2), 307; https://doi.org/10.3390/vaccines11020307 - 30 Jan 2023
Cited by 8 | Viewed by 6552
Abstract
(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity [...] Read more.
(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
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7 pages, 237 KiB  
Brief Report
Does Perioperative Administration of Rabies Vaccine in Dogs Undergoing Surgical Sterilization Induce an Adequate Antibody Response?
by Andrea Peda, Paulina Samaniego, Christy Daugherty, Theresa Wood, Chengming Wang and Darryn Knobel
Vaccines 2023, 11(9), 1418; https://doi.org/10.3390/vaccines11091418 - 25 Aug 2023
Viewed by 1903
Abstract
High-volume spay/neuter events may facilitate access to free-roaming dogs to administer rabies vaccination, but important questions remain regarding the effect of surgery and anesthesia on the immune response to a vaccine administered in the perioperative period. This study evaluated the immunogenicity of primary [...] Read more.
High-volume spay/neuter events may facilitate access to free-roaming dogs to administer rabies vaccination, but important questions remain regarding the effect of surgery and anesthesia on the immune response to a vaccine administered in the perioperative period. This study evaluated the immunogenicity of primary rabies vaccination in dogs when administered during the immediate perioperative period at the time of surgical sterilization (ovariohysterectomy/orchidectomy). Healthy dogs of both sexes presenting for surgical sterilization who had never been vaccinated against rabies virus were eligible for enrollment in the study. Fifty dogs ranging in age from 5 to 96 months were enrolled and were vaccinated against rabies virus during the recovery period following anesthesia and surgery. Rabies virus neutralizing antibody (RVNA) titers were measured preoperatively and 28 days postoperatively. This cohort was compared to a historical control cohort of 57 dogs who received primary rabies vaccination for travel purposes and had RVNA titers measured at the same laboratory as the study group 28–35 days post-vaccination. After controlling for age and sex, there was no statistically significant difference in immunogenicity of a rabies vaccine administered to dogs during the perioperative period in comparison to dogs that received the rabies vaccine for travel alone in the absence of surgery. Perioperative administration of a rabies vaccine in dogs undergoing surgical sterilization induces an adequate antibody response. We recommend that rabies vaccine be administered perioperatively during spay/neuter campaigns in canine rabies endemic areas if other opportunities to access veterinary care and rabies vaccination are limited. Full article
(This article belongs to the Special Issue Rabies Vaccines and Immunoglobulins)
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