Impact of Molecular Modifications on the Immunogenicity and Efficacy of Recombinant Raccoon Poxvirus-Vectored Rabies Vaccine Candidates in Mice

Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work.

Atypical paralytic rabies — A case-study from Kerala, India

Rabies, though endemic in India, has been a disease of low public health priority throughout the years. Being a non-notifiable disease together with limited diagnostic facilities, it often ends up in under-reporting of cases, especially atypical rabies. Failure of complete rabies Post Exposure Prophylaxis (PEP) with Immunoglobulin has been rarely reported. We report a case of atypical rabies in a 60-year-old man from a rural village in Kerala, who presented with fever, paralysis of limbs, fluctuating consciousness, phonophobia and without classical signs of hydrophobia and aerophobia 22 days after dog bite. The case is supplemented with supportive Magnetic Resonance Imaging (MRI) findings and corneal imprint smear Fluorescent Antibody Test (FAT). The death of the patient on the 28th day of exposure despite early PEP with rabies vaccine and immunoglobulin is suggestive of PEP failure. The case study stresses on the need in making rabies a notifiable disease in the study setting, encouraging disease specific investigation, ensuring availability of vaccine and immunoglobulins with adherence to standardized treatment protocols.Deviations from the recommended protocol for Animal bite management, such as delay in seeking PEP, lack of or improper administration of rabies immunoglobulin (e.g. missing out bite sites), lack of or improper primary wound care, and/or poor-quality rabies vaccine, may lead to death.

Oral vaccination of foxes and raccoon dogs against rabies with the 3rd generation oral rabies virus vaccine, SPBN GASGAS, in Finland

Background To prevent re-emergence of wildlife-mediated rabies in Finland, oral rabies vaccine baits are distributed every year during autumn in southern Finland in a vaccination zone bordering Russia. Recently, Finland introduced a 3rd generation oral rabies virus vaccine bait. By analysing bait uptake and seroconversion in red foxes and raccoon dogs, the field efficacy of this new vaccine strain, SPBN GASGAS, was compared with the originally used highly efficacious 1st generation vaccine SAD B19. Results Overall, 74.6% and 53.9% of the animals submitted from the vaccination area after the campaigns (2017–2019) tested positive for the presence of the bait marker and anti-rabiesvirus antibodies, respectively. No significant difference was observed between years, species and vaccine. Conclusions The field performance of the highly attenuated 3rd generation oral rabies vaccine, SPBN GASGAS, in terms of bait uptake and seroconversion was similar to the 1st generation vaccine, SAD B19, and therefore offers a suitable alternative.

Forecasting the Anti-Rabies Vaccine Demand at Jawaharlal Medical College and Hospital, Ajmer, Rajasthan: A Comparative Analysis based on Time Series Model

Background: In India, high mortality and morbidity rates of human rabies is observed. Hence, a structured surveillance system is yet to be put in place for public health discussion. At the tertiary care hospital and all public health centres, requirement of anti-rabies vaccine is needed in advance to predict the upcoming months coverage so that wastage of vaccine is minimum. Objective: To find a suitable model for forecasting the appropriate stock of anti-rabies vaccines to avoid shortage and over-supply at anti rabies clinic. Methods and Material: This was a record based cross sectional study, conducted at anti rabies clinic of Jawaharlal Nehru Medical College and Hospital, Ajmer. Data of used anti rabies vaccine was taken from immunization inventory during the period from 2017 to 2020. Time series analysis based on Holt-Winter and Box-Jenkins methods were carried out to predict the need of vaccine. Results: Study series was not stationary and stationarity was observed by taken difference in the observation between two consequent months. Residuals of the series were normally distributed and independent to each other. ARIMA(0, 1, 1) was the best model in comparison to Holt-Winter model for prediction because of low value of model selection criterion. The forecasted value for anti-rabies vaccine was done for the year 2021. Conclusions: The following study concluded that time series can be used as a tool to forecast anti-rabies vaccine coverage and will help the policy makers to formulate appropriate plans and strategies and improve the management of vaccination resources and inventory.

Investigating the Efficacy of a Canine Rabies Vaccine Following Storage Outside of the Cold-Chain in a Passive Cooling Device

Background: Thermostable vaccines greatly improved the reach and impact of large-scale programmes to eliminate infectious diseases such as smallpox, polio, and rinderpest. A study from 2015 demonstrated that the potency of the Nobivac® Rabies vaccine was not impacted following experimental storage at 30°C for 3 months. Whether the vaccine would remain efficacious following storage under more natural, fluctuating temperature conditions remains unknown. We carried out a randomised controlled non-inferiority trial to compare serological responses in dogs following vaccination with doses stored under cold chain conditions with those stored within a locally made Passive Cooling Device (“Zeepot”) under fluctuating temperature conditions.Materials and Methods: Nobivac® Rabies vaccine was stored under either cold-chain conditions or within the Zeepot for 2 months. Daily ambient temperatures and temperatures within the Zeepot were recorded every 3 h. Following storage, 412 domestic dogs were randomly assigned to receive either cold-chain or Zeepot stored Nobivac® Rabies vaccine. Baseline and day 28-post vaccination blood samples were collected. Serological analysis using the Fluorescent Antibody Virus Neutralisation assay was carried out with a threshold of 0.5 IU/ml to determine seroconversion. In addition, the impact of dog Body Condition Score, sex, and age on seroconversion was examined.Results: The serological response of dogs vaccinated using Nobivac® Rabies vaccine stored within the Zeepot was not inferior to the response of dogs vaccinated using cold-chain stored vaccine (z = 1.1, df = 313, p-value = 0.25). Indeed, the 28-day post-vaccination group geometric mean titre was 1.8 and 2.0 IU/ml for cold-chain vs. non-cold-chain storage, respectively. Moreover, the percentage of dogs that seroconverted in each arm was almost identical (85%). There was a positive linear trend between Body Condition Score (O.R. 2.2, 95% CI: 1.1–5.1) and seroconversion, suggesting dogs of poor condition may not respond as expected to vaccination.Conclusions: Our study demonstrated the potency of Nobivac® Rabies vaccine is not impacted following storage under elevated fluctuating temperatures within a Zeepot. These results have potentially exciting applications for scaling up mass dog vaccination programmes in low-and-middle income countries, particularly for hard-to-reach populations with limited access to power and cold-chain vaccine storage.

Rabies Vaccine Disposition: Trends in Vaccination Among Israeli Travelers

Travelers are a risk-group for rabies; however, few are protected. We describe changes in pre-travel vaccination rates and post-travel referrals after animal contact. We conducted a nationwide, retrospective study for 2014–2018. The ratio of rabies vaccine courses distributed to travelers and the number of Israeli-tourist-entries to endemic countries was calculated, as was the proportion of travelers referred to a post-travel clinic after animal contact. During the study period, the ratio of pre-travel vaccine courses distributed nationally to outgoing tourism to endemic countries was stable at ≈0.7%; 13% of 256,969 pre-travel consultations included recommendation for rabies vaccination. Backpackers were more likely to be immunized (40.2%) than business travelers (4.4%) or travelers planning organized/high-end travel (2.0%). However, rates of rabies vaccination among backpackers showed a decline during the study period. Post-travel referrals after animal contact were stable at 2% of all referrals; most were exposed in Asia (69.5%) and 51% were bitten by dogs. Only 38% received post-exposure prophylaxis abroad. We conclude that only a minority of Israeli travelers, including backpackers, receive rabies pre-exposure prophylaxis. The proportion of travelers with potentially rabid animal contact is not decreasing; however, many exposed travelers do not receive post-exposure prophylaxis during travel. Because rabies control programs have been compromised in endemic countries during the COVID-19 pandemic, the need to provide rabies protection to travelers has become more urgent. After the ACIP’s adoption of the World Health Organization’s (WHO) 2-dose regimen, a revision of current vaccine guidelines is required to provide a simplified, more inclusive rabies vaccine policy.