Rabies Antibody Research Articles

Rabies Vaccination for Sheep and Goats: Influence of Booster on Persistence of Antibody Response

Infrequent rabies cases occur in Israel, endangering humans and animals. While dogs receive mandatory vaccinations, farm animals are vaccinated voluntarily. However, optimal vaccination protocol for small ruminants is lacking. The aim of this study was to test the immunological responses to the rabies vaccine, with or without a booster, in sheep and goats; 70 ewes and 49 does participated in the trial. Following the first vaccine, 88% of the ewes and 100% of the does had a sufficient level of rabies antibodies (>0.5 IU/mL) 30 days post-vaccination. A year later, 82% of the ewes that had received a booster dose remained protected, whereas 46% of the non-boosted ewes had a sufficient antibody level. For does, 83% of those receiving a booster maintained sufficient antibody levels 1 year later; 80% of the non-boosted does remained protected, demonstrating no significant contribution of the booster dose in this group of goats. However, while the initial immunological response of the does was higher, the change in response between 1 month and 12 months post-vaccination differed significantly between species, with a greater titer reduction in the does. Differential immunological responses between individuals and between species warrant longer-term studies to recommend a proper vaccine protocol for each species.

Standardization And Evaluation Of An In-House ELISA For The Detection Of Rabies Antibody In A Tertiary Care Centre In South India

BackgroundRapid fluorescent focus inhibition test (RFFIT), a neutralization-based assay for detecting rabies antibodies, is the gold standard. The National Action Plan for Dog Mediated Rabies Elimination (NAPRE) is a national program that strategizes the establishment of enzyme-linked immunosorbent assays (ELISA) to detect rabies antibodies. ObjectiveWe developed an in-house ELISA to screen for rabies antibodies using rabies vaccine antigen to study vaccine response among health care workers (HCWs) who received pre-exposure prophylaxis and a few animal bite victims who received post-exposure prophylaxis with rabies vaccine. Study designA prospective study was carried out from April to September 2023 at the Department of Clinical Virology of a tertiary care center in South India. A total of 161 serum specimens, which included 155 serum samples from study participants and 6 samples from a reference laboratory (as controls), were obtained during the study period. Rabies antibody was determined by the in-house standardized ELISA developed using the rabies vaccine and compared with the reference assay, RFFIT. The accuracy indices of the in-house ELISA were estimated by MedCalc software (version 22.023). ResultsA panel of 86 positive and 75 negative serum samples was used for evaluating the in-house standardized ELISA. The sensitivity, specificity, positive and negative predictive values of the in-house ELISA were 98.8%, 100%, 100%, and 98.7% respectively. The accuracy of the in-house ELISA is 99.4%. ConclusionELISA can be a practically feasible and less expensive assay compared to RFFIT which is a cumbersome procedure with a long turn-around time of 3-4 days.

Biology, Shelter Use and Rabies Antibodies in the Hairy-Legged Vampire Bat, Diphylla ecaudata, in Cohabitation with Desmodus rotundus: A Large Colony in a Man-Made Building in Southeastern Brazil, with Comments on Conservation

Biology, Shelter Use and Rabies Antibodies in the Hairy-Legged Vampire Bat, Diphylla ecaudata, in Cohabitation with Desmodus rotundus: A Large Colony in a Man-Made Building in Southeastern Brazil, with Comments on Conservation

Imaging in Rabies Encephalitis

Rabies encephalitis is a fatal disease with few reports of survival being available. Even though rabies is definitively confirmed by virus isolation from biological samples or detection of the rabies antigen or antibodies, diagnosis is essentially clinical and magnetic resonance imaging (MRI) brain can be used as one of the modalities of investigation for the early detection of rabies and for distinguishing it from other encephalitis.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP—to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation—to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

No Evidence of Rabies Exposure in Wild Marmosets (Callithrix jacchus) of Northeast Brazil.

Rabies transmitted by wildlife is the main source of human rabies mortality in Latin America and considered an emerging disease. The common marmoset Callithrix jacchus of Brazil is the only known primate reservoir of rabies worldwide. We tested whether alive free-ranging C. jacchus were exposed to rabies in four northeast states that have previously reported rabies-positive dead C. jacchus (Pernambuco and Bahia) or not (Paraíba and Rio Grande do Norte). Our results show no evidence of rabies antibodies or infection in the sampled C. jacchus, suggesting that apparently healthy marmosets are not widely exposed to rabies over their natural range.

Evaluation of an iELISA for detection and quantification of rabies antibodies in domestic dog sera

Many rabies endemic-countries have recognized rabies as a public health problem that can be eliminated. As a result, some countries have started implementing small-scale vaccination programs with the aim of scaling them up. Post-vaccination serological monitoring is crucial to assess the efficacy of these programs. The recommended serological tests, the rapid fluorescent focus inhibition test, and the fluorescent antibody virus neutralization (FAVN) are accurate; however, the procedures require considerable expertise and must be carried out in high containment facilities, which are often not available in rabies endemic countries. Given these constraints, enzyme linked immunosorbent assays (ELISAs) have been considered as alternative methods to neutralization tests. This is the first study to evaluate, under field conditions, the performance of the commercial rabies indirect-ELISA (iELISA), the PlateliaTM Rabies II kit ad usum Veterinarium kit, using sera from domestic dogs. Serum samples were collected from two groups of community dogs in northern Tanzania: i) dogs with no history of vaccination against rabies (n = 100) and ii) dogs vaccinated with the Nobivac Canine Rabies® vaccine (n = 101) four weeks previously. When compared to the gold standard FAVN test, the iELISA was found to be 99% specific and 98% sensitive and there was a significant correlation between the two tests (p < 0.001, r = 0.92). Given these findings, we conclude that the PlateliaTM Rabies II kit ad usum Veterinarium can be considered a valuable tool for the rapid assessment of vaccination status of animals in vaccination programs.

Efficiency Comparative Approach of Plant-Produced Monoclonal Antibodies against Rabies Virus Infection.

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.

An Oil-Based Adjuvant Improves Immune Responses Induced by Canine Adenovirus-Vectored Vaccine in Mice.

There is a significant need for highly effective vaccines against emerging and common veterinary infectious diseases. Canine adenovirus type 2 (CAV2) vectors allow rapid development of multiple vaccines and have demonstrated their potential in animal models. In this study, we compared the immunogenicity of a non-replicating CAV2 vector encoding the rabies virus glycoprotein with and without MontanideTM ISA 201 VG, an oil-based adjuvant. All vaccinated mice rapidly achieved rabies seroconversion, which was associated with complete vaccine protection. The adjuvant increased rabies antibody titers without any significant effect on the anti-CAV2 serological responses. An RT2 Profiler™ PCR array was conducted to identify host antiviral genes modulated in the blood samples 24 h after vaccination. Functional analysis of differentially expressed genes revealed the up-regulation of the RIG-I, TLRs, NLRs, and IFNs signaling pathways. These results demonstrate that a water-in-oil-in-water adjuvant can shape the immune responses to an antigen encoded by an adenovirus, thereby enhancing the protection conferred by live recombinant vaccines. The characterization of early vaccine responses provides a better understanding of the mechanisms underlying the efficacy of CAV2-vectored vaccines.

Immune-adjuvant effect of vitamin A and probiotics supplementation on humoral response to cell culture rabies vaccine in rabbits.

This study was carried out to evaluate the effects of vitamin A (Vit A) and probiotic co-supplementation with rabies vaccine on humoral immune response in New Zealand white (NZW) rabbits. For this experiment, 54 rabbits were randomized into six experimental and three control groups. Mixed cultures of commercial probiotics supplements and a dose of Vit A were administered to each animal. Results were compared with the control group fed with only basal diet. Animals in different treatment groups showed significantly higher sero-conversions against rabies vaccine. There was a significant increase (p < 0.001) in the titers of rabies antibodies in all treatment groups on 14th and 35th days than control C3 group. Both commercial probiotics irrespective of brand increase the humoral immune response of rabbits against rabies vaccine. The mean titer values of all groups G1-G6 and sub-controls (C1, C2) were generally above 3.6 EU/ml on day 14th and between 3.7 and 3.9 EU/ml, showing highest sero-conversion on 35th day than mean titer of C3 control = 3.091 and 3.505 EU/ml respectively on both days. The maximum titer values were obtained with the addition of organic carrots to the daily diet. These results suggest that simple dietary interventions using probiotics and Vit A in natural form may enhance the efficacy of rabies vaccine in the host. These cost-effective strategies can be applied for getting higher yields of polyclonal antibody production in animal models, thus providing promising means of improving the final product yield and can be adopted easily by the manufacturers.

Immune response after rabies pre-exposure prophylaxis and a booster dose in Australian bat carers.

Periodic vaccination against rabies is essential for individuals at continuing risk of rabies exposure. There is limited evidence on long-term immunogenicity after a 3-dose intramuscular (3IM) pre-exposure prophylaxis (PrEP) and single IM booster dose, thus current guideline recommendations differ in the interval for serology tests following PrEP and boosters. This study investigated post-PrEP and post-booster persistence of antibodies in Australian bat carers. Bat carers who received 3IM PrEP/booster doses and had post-PrEP/booster serology test results were included. The proportion of antibody-negative (<0.5 EU/mL) individuals after PrEP/booster dose were examined. Three hundred and five participants (65.6% females, median age at PrEP 43.1 years) were included. The proportion who were antibody-negative varied depending on the time between 3IM PrEP and the serology test: 8.0% <1 year, 29.8% 1-2 years, 21.2% 2-3 years and 7.7% >3 years. Ninety-one participants receiving booster doses were further assessed. Only one participant was antibody-negative at >3 years after receiving one IM booster dose. Our findings support that a serology test should be performed 1 year after 3IM PrEP, followed by first booster if required. Rabies antibodies persist for many years after receiving the booster doses. The interval between subsequent serology tests and the first booster dose should be no longer than 3 years. Future studies are required to provide more insight into the most appropriate timing of subsequent boosters.

Comparing Control Intervention Scenarios for Raccoon Rabies in Southern Ontario between 2015 and 2025.

The largest outbreak of raccoon rabies in Canada was first reported in Hamilton, Ontario, in 2015 following a probable translocation event from the United States. We used a spatially-explicit agent-based model to evaluate the effectiveness of provincial control programs in an urban-centric outbreak if control interventions were used until 2025, 2020, or never used. Calibration tests suggested that a seroprevalence of protective rabies antibodies 2.1 times higher than that inferred from seroprevalence in program assessments was required in simulations to replicate observed raccoon rabies cases. Our simulation results showed that if control interventions with an adjusted seroprevalence were used until 2025 or 2020, the probability of rabies elimination due to control intervention use was 49.2% and 42.1%, respectively. However, if controls were never used, the probability that initial rabies cases failed to establish a sustained outbreak was only 18.2%. In simulations where rabies was not successfully eliminated, using control interventions until 2025 resulted in 67% fewer new infections compared to only applying controls until 2020 and in 90% fewer new infections compared to no control intervention use. However, the model likely underestimated rabies elimination rates since we did not adjust for adaptive control strategies in response to changes in rabies distributions and case numbers, as well as extending control interventions past 2025. Our agent-based model offers a cost-effective strategy to evaluate approaches to rabies control applications.

Evaluation of the immune response of dogs after a mass vaccination campaign against rabies in Tunisia

BackgroundRabies (RABV) is an enzootic disease in Tunisia, with dogs being the primary reservoir. Vaccinating dogs is the key to eradicate rabies. Regional Veterinary Services conduct nationwide immunisation campaigns on an annual basis. Evaluation of the immune response is still important to make sure that the vaccination is effective in the conditions of the Tunisian field. In this paper, the FAVN technique was used to test rabies antibody dynamics in dogs from three distinct Tunisian areas observed for one year following a mass vaccination campaign.ResultsOn day 30 after vaccination, 75% of all dogs vaccinated during the campaign were sero-positive (titres greater than or equal to 0.5 transformed IU/ml). On day 180, 48% of all dogs were sero-positive. Only 25.6% of primary-vaccinated dogs remained sero-positive on day 180 and 7% on day 365, whereas 91% of previously sero-positive dogs remained sero-positive on day 365.ConclusionsAlthough a single rabies vaccine is successful at stimulating an immunological response, it is recommended that primary-vaccinated dogs have a second booster between one and three months after the initial vaccination to maintain seropositivity. To achieve the rabies eradication objective, all dogs should receive an annual booster to maintain effective immunological protection.

Multifactorial Influences on Rabies Antibodies in Moroccan Exported Dogs

Multifactorial Influences on Rabies Antibodies in Moroccan Exported Dogs

Rabies Virus Neutralizing Activity, Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults

ObjectivePreliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. MethodsSubjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days –7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. ResultsAll 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU /mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0–14 days and 0–42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. ConclusionThe rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.

Seroprevalence and predisposing factors of rabies antibodies in unvaccinated dogs in Sierra Leone.

This study determines the seroprevalence and associated factors of rabies in unvaccinated dogs in Sierra Leone. Rabies control is poorly coordinated in Sierra Leone which was ranked as the third hungriest country in the world. Due to limited access to rabies vaccines, the need for comprehensive serological data on dogs for control of the disease is expedient. A random multistage technique considering high, medium and low incident areas of rabies cases in dog-populated communities was adopted. Samples were collected from dogs with owners which were at least 1-year old. Samples were analysed using a commercial ELISA in accordance to manufacturer's instructions. 25.2% of the total 270 samples tested positive for the presence of rabies antibodies. Kenema district had the highest number of positive samples, followed by the Bombali district and Moyamba district the least. Predisposing factors, including sex, the status of castration, the type of settlement, district and the availability of fences at locations where dogs are kept, had significant effects (p<0.05) on the exposure of dogs to rabies. The 25.2% antibody seroprevalence obtained is very low. Concerted effort should be made to enhance rabies vaccination through an awareness campaign and provision of vaccine to dog owners. Good waste disposal and management practices to reduce open garbage disposal in communities will go a long way to limit the stray-dog population and minimize rabies outbreaks especially in third-world countries where rabies vaccines are not accessible.

Ecological determinants of rabies virus dynamics in vampire bats and spillover to livestock.

The pathogen transmission dynamics in bat reservoirs underpin efforts to reduce risks to human health and enhance bat conservation, but are notoriously challenging to resolve. For vampire bat rabies, the geographical scale of enzootic cycles, whether environmental factors modulate baseline risk, and how within-host processes affect population-level dynamics remain unresolved. We studied patterns of rabies exposure using an 11-year, spatially replicated sero-survey of 3709 Peruvian vampire bats and co-occurring outbreaks in livestock. Seroprevalence was correlated among nearby sites but fluctuated asynchronously at larger distances. A generalized additive mixed model confirmed spatially compartmentalized transmission cycles, but no effects of bat demography or environmental context on seroprevalence. Among 427 recaptured bats, we observed long-term survival following rabies exposure and antibody waning, supporting hypotheses that immunological mechanisms influence viral maintenance. Finally, seroprevalence in bats was only weakly correlated with outbreaks in livestock, reinforcing the challenge of spillover prediction even with extensive data. Together our results suggest that rabies maintenance requires transmission among multiple, nearby bat colonies which may be facilitated by waning of protective immunity. However, the likelihood of incursions and dynamics of transmission within bat colonies appear largely independent of bat ecology. The implications of these results for spillover anticipation and controlling transmission at the source are discussed.

Review of CDC's Suspension of and Advance Written Approval Process for Dogs Entering the United States from Egypt - May 2019-December 2020.

Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015–2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019–December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC’s ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.

Serological Evidence of Canine Rabies and Dog Owners’ Response about the Disease in Selected Veterinary Clinics within Jos Metropolis, Nigeria

Canine rabies is endemic in Nigeria as evident by several reports, however, it is a vaccine preventable disease in both animals and man. Dog owners’ knowledge, attitude and practice (KAP) toward rabies is instrumental to a successful rabies prevention and control measures against transmission. This study determined the prevalence of rabies antibodies in owned dogs and assessed KAPof dog owners toward rabies in Jos Metropolis, Nigeria in a cross sectional study conducted between January, 2019 and March, 2019. Sera from 100 dog blood samples were collected but only 92 samples were subjected to Enzyme Linked Immunosorbent Assay (ELISA) using Rabies Virus IgG Ab (DEMEDITEC Diagnostics GmbH, Lise-Meitner Strase 2, 24145 Kiel, Germany). Zoographic data obtained showed 61 (66.3%) dogs sampled were female, the dogs were kept majorly for security (n=54) and breeding (n=28). Vaccination records revealed that 13 (14.1%) of the dogs were not vaccinated against rabies. Analysis revealed good KAP scores of the dog owners at 75%, 95% and 95%, respectively. There was a statistically significant association between qualification (no formal education) and categorised attitude scores (P = 0.003) also between no formal education and categorised practice scores (P = 0.026). In conclusion, majority (93.5%) of the dogs tested had rabies antibodies which may indicate previous vaccination. Although dog owners KAP were good, majority (62%) were ignorant that rabies has no cure. Public health awareness on the dangers of rabies and annual dog anti-rabies vaccination toward elimination of dog-mediated human rabies, still needs to be intensified and sustained.

Rabies immune status of vaccinated and unvaccinated dogs in Kwara State, Nigeria

Rabies is one of the deadliest zoonoses that have existed for decades, affecting wide range of hosts globally. In Nigeria, there is paucity of data on routine antibody check of antirabies vaccinated dogs as quality assurance. This study was designed to investigate the seroprevalence of canine rabies virus in both vaccinated and unvaccinated dogs within Kwara State, Nigeria. A total of one hundred and eighty-two (182) blood samples collected from dogs were transported to the Virology and Immunology Laboratory of the University of Ilorin Veterinary Teaching Hospital for processing. Sera were harvested from the blood samples and rabies IgG was qualitatively determined by enzyme-linked immunosorbent assay (ELISA) technique. Overall seroprevalence of 11% (20/182) was recorded in this study. One hundred and twenty-one (66.5%) and Sixty-one (33.5%) of the dogs used in this study had vaccination and non-vaccination status respectively. The study also revealed that several dogs (78.7%; 48/61) that were said to be vaccinated did not have rabies antibodies while some unvaccinated dogs (5.8%; 7/121) had rabies antibodies. There was a significant (χ2 = 11.177, df = 4, P = 0.025) association between age group and rabies virus antibodies detection. The same significant (χ2 = 9.995, df = 1, P = .002) association was observed for vaccination status of dogs sampled. On the other hand, sex has no significant (χ2 = 0.71, df = 1, P = .790) association with rabies virus antibodies. Poor attitude to vaccination of dogs used for hunting in rural and semi-urban areas was generally observed compared to dogs kept for other purposes in urban areas. There is need for increased rabies awareness campaign, vaccine subsidies, and wider sero-surveillance activities engaging the relevant stakeholders with government sponsorship.