Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans

Mansfield, Karen L.; Andrews, Nick; Goharriz, Hooman; Goddard, Trudy; McElhinney, Lorraine M.; Brown, Kevin E.; Fooks, Anthony R.

doi:10.1016/j.vaccine.2016.09.058

Cited by 36 publications

(25 citation statements)

References 31 publications

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“…Since the implementation (April 2018–March 2019), no single case of rabies has been reported in humans or animals in Moshi by the public health and veterinary authorities [33]. Furthermore, in previous studies, other factors have been linked to idiosyncratic reactions and atypical antibody responses including the following: (a): situations where temporality and longevity of humoral responses vary across individuals [34]; (b) abortive rabies infection [35]; and (c) previous predominant cellular response inhibiting humoral response [36]. Similar observations to findings from our study have also been presented by other researchers [37,38,39].…”

Section: Discussionmentioning

confidence: 99%

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

Mtui-Malamsha¹,

Sallu²,

Mahiti

et al. 2019

IJERPH

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Approximately 1500 people die annually due to rabies in the United Republic of Tanzania. Moshi, in the Kilimanjaro Region, reported sporadic cases of human rabies between 2017 and 2018. In response and following a One Health approach, we implemented surveillance, monitoring, as well as a mass vaccinations of domestic pets concurrently in >150 villages, achieving a 74.5% vaccination coverage (n = 29, 885 dogs and cats) by September 2018. As of April 2019, no single human or animal case has been recorded. We have observed a disparity between awareness and knowledge levels of community members on rabies epidemiology. Self-adherence to protective rabies vaccination in animals was poor due to the challenges of costs and distances to vaccination centers, among others. Incidence of dog bites was high and only a fraction (65%) of dog bite victims (humans) received post-exposure prophylaxis. A high proportion of unvaccinated dogs and cats and the relative intense interactions with wild dog species at interfaces were the risk factors for seropositivity to rabies virus infection in dogs. A percentage of the previously vaccinated dogs remained unimmunized and some unvaccinated dogs were seropositive. Evidence of community engagement and multi-coordinated implementation of One Health in Moshi serves as an example of best practice in tackling zoonotic diseases using multi-level government efforts. The district-level establishment of the One Health rapid response team (OHRRT), implementation of a carefully structured routine vaccination campaign, improved health education, and the implementation of barriers between domestic animals and wildlife at the interfaces are necessary to reduce the burden of rabies in Moshi and communities with similar profiles.

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Section: Discussionmentioning

confidence: 99%

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

Mtui-Malamsha¹,

Sallu²,

Mahiti

et al. 2019

IJERPH

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“…Failure of postexposure prophylaxis has been reported in several cases (4). In addition, low-, medium-, and high-responder profiles for various vaccines have been demonstrated (5,6). Therefore, quantitation of an antirabies antibody is necessary to determine the immune status and to ensure that a sufficient amount of protective antibody has been produced to prevent and treat rabies infection.…”

Section: Introductionmentioning

confidence: 99%

A Cost Effective Easy Competitive Enzyme-Linked Immunosorbent Assay Suitable for Monitoring Protective Immunity against the Rabies Virus in the Serum of Humans and Dogs

et al. 2019

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The coverage of rabies vaccinations has been reported at 70-80% of dogs in annual reports. However, there are still outbreaks of rabies among humans and dogs in Thailand, thus indicating the necessity of ensuring seroprevalence in vaccinated dogs and efficacy of human immunization. A cost effective easy competitive enzyme-linked immunosorbent assay (CEE-cELISA) was developed here for monitoring protective immunity against the rabies virus in human and dog serum samples using monoclonal antibody clone 1-46-12, which recognizes a conformational epitope of the rabies G protein. The ELISA plate is coated with the whole viral antigen from a commercial vaccine. The serotiter measured by the CEE-cELISA and by the gold standard assay (rapid fluorescent focus inhibition test), detecting the neutralizing antibody, showed a strong correlation, with an R value of 0.958 and 0.931 in humans and dogs, respectively. These correlations were detected in the serum samples from humans and dogs at antibody concentrations up to 100 and 10 IU/ml, respectively. This CEE-cELISA could be an alternative assay for evaluating mass rabies vaccination rapidly at a low cost as well as for detecting antirabies antibodies in the serum of not only humans but also other animal species.

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“…It is recommended that previous PrEP recipients who then receive a dog bite should still receive PEP, but this ‘post-PrEP PEP’ is an abbreviated and much less expensive course over one or two visits, without RIG [ 9 ]. Importantly, data suggest that PrEP alone —without any PEP—can achieve potentially protective antibody titers lasting many years [ 16 , 17 ]. This suggests that PrEP may provide substantial benefit even in contexts in which the reliable availability of PEP cannot be assured.…”

Section: Introductionmentioning

confidence: 99%

A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis

et al. 2018

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BackgroundEstimates of current global rabies mortality range from 26,000 to 59,000 deaths per annum. Although pre-exposure prophylaxis using inactivated rabies virus vaccines (IRVs) is effective, it requires two to three doses and is regarded as being too expensive and impractical for inclusion in routine childhood immunization programmes.Methodology/ Principal findingsHere we report the development of a simian-adenovirus-vectored rabies vaccine intended to enable cost-effective population-wide pre-exposure prophylaxis against rabies. ChAdOx2 RabG uses the chimpanzee adenovirus serotype 68 (AdC68) backbone previously shown to achieve pre-exposure protection against rabies in non-human primates. ChAdOx2 differs from AdC68 in that it contains the human adenovirus serotype 5 (AdHu5) E4 orf6/7 region in place of the AdC68 equivalents, enhancing ease of manufacturing in cell lines which provide AdHu5 E1 proteins in trans.We show that immunogenicity of ChAdOx2 RabG in mice is comparable to that of AdC68 RabG and other adenovirus serotypes expressing rabies virus glycoprotein. High titers of rabies virus neutralizing antibody (VNA) are elicited after a single dose. The relationship between levels of VNA activity and rabies virus glycoprotein monomer-binding antibody differs after immunization with adenovirus-vectored vaccines and IRV vaccines, suggesting routes to further enhancement of the efficacy of the adenovirus-vectored candidates. We also demonstrate that ChAdOx2 RabG can be thermostabilised using a low-cost method suitable for clinical bio-manufacture and ambient-temperature distribution in tropical climates. Finally, we show that a dose-sparing effect can be achieved by formulating ChAdOx2 RabG with a simple chemical adjuvant. This approach could lower the cost of ChAdOx2 RabG and other adenovirus-vectored vaccines.Conclusions/ SignificanceChAdOx2 RabG may prove to be a useful tool to reduce the human rabies death toll. We have secured funding for Good Manufacturing Practice- compliant bio-manufacture and Phase I clinical trial of this candidate.

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Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans

Cited by 36 publications

References 31 publications

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

Ecological and Epidemiological Findings Associated with Zoonotic Rabies Outbreaks and Control in Moshi, Tanzania, 2017–2018

A Cost Effective Easy Competitive Enzyme-Linked Immunosorbent Assay Suitable for Monitoring Protective Immunity against the Rabies Virus in the Serum of Humans and Dogs

A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis

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