Evaluation of Rabies Biologics against Irkut Virus Isolated in China

Liu, Ye; Chen, Qi; Zhang, Fei; Zhang, Shoufeng; Li, Nan; Long, Hai; Wang, Ying; Zhang, Jinxia; Hu, Rongliang

doi:10.1128/jcm.01565-13

Cited by 17 publications

(13 citation statements)

References 25 publications

(31 reference statements)

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“…However, for IRKV infection it was shown that only routine PrEP (3 vaccine doses, on days 0, 7, and 28) induced strong protection against IRKV infection, while only very high doses of RABV immunoglobulins conferred partial protection of animals 27 . Similar experimental studies are needed to confirm cross-protection for BBLV.…”

Section: Discussionmentioning

confidence: 99%

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against differentLyssavirusspecies

Malerczyk

Freuling

Gniel

et al. 2014

Human Vaccines & Immunotherapeutics

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Background: Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2.Material & Methods: Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV.Results: Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate).Conclusion: Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research.

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Section: Discussionmentioning

confidence: 99%

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against differentLyssavirusspecies

Malerczyk

Freuling

Gniel

et al. 2014

Human Vaccines & Immunotherapeutics

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“…Finland experienced a human death from EBLV-2 in 1985 [ 9 , 10 ], and better knowledge of the effectiveness of cross-protection is therefore needed to predict the impact of rabies vaccination if exposed to infected bats, as EBLV-2 appears to be enzootic at least in some areas in Finland [ 15 , 16 ]. The immune response elicited by RABV-based rabies vaccines has been shown to be capable of cross-protection against those lyssaviruses in phylogroup I, but not for those that do not belong to this phylogroup [ 42 – 45 ]. However, even though EBLV-2 belongs to the same phylogroup I as RABV, the protection induced by rabies vaccines has only been limited in an experimental virus challenge study in mice, even with the production of VNAs [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Possible exposure to other lyssaviruses than RABV has especially raised concerns over whether RABV-based vaccines offer sufficient cross-protection and whether a higher cut-off for protection against EBLV-2 would be required. Studies have suggested that either higher serum VNA titres [ 34 ] or higher doses of rabies immunoglobulins are required [ 45 ] in humans. There is marked individual variation in the comparative neutralisation patterns of human sera against different lyssaviruses [ 34 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of rabies vaccines in dogs and cats and protection in a mouse model against European bat lyssavirus type 2

et al. 2017

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BackgroundRabies is preventable by pre- and/or post-exposure prophylaxis consisting of series of rabies vaccinations and in some cases the use of immunoglobulins. The success of vaccination can be estimated either by measuring virus neutralising antibodies or by challenge experiment. Vaccines based on rabies virus offer cross-protection against other lyssaviruses closely related to rabies virus. The aim was to assess the success of rabies vaccination measured by the antibody response in dogs (n = 10,071) and cats (n = 722), as well as to investigate the factors influencing the response to vaccination when animals failed to reach a rabies antibody titre of ≥ 0.5 IU/ml. Another aim was to assess the level of protection afforded by a commercial veterinary rabies vaccine against intracerebral challenge in mice with European bat lyssavirus type 2 (EBLV-2) and classical rabies virus (RABV), and to compare this with the protection offered by a vaccine for humans.ResultsA significantly higher proportion of dogs (10.7%, 95% confidence interval CI 10.1–11.3) than cats (3.5%; 95% CI 2.3–5.0) had a vaccination antibody titre of < 0.5 IU/ml. In dogs, vaccination with certain vaccines, vaccination over 6 months prior the time of antibody determination and vaccination of dogs with a size of > 60 cm or larger resulted in a higher risk of failing to reach an antibody level of at least 0.5 IU/ml. When challenged with EBLV-2 and RABV, 80 and 100% of mice vaccinated with the veterinary rabies vaccine survived, respectively. When mice were vaccinated with the human rabies vaccine and challenged with EBLV-2, 75–80% survived, depending on the booster. All vaccinated mice developed sufficient to high titres of virus-neutralising antibodies (VNA) against RABV 21–22 days post-vaccination, ranging from 0.5 to 128 IU/ml. However, there was significant difference between antibody titres after vaccinating once in comparison to vaccinating twice (P < 0.05).ConclusionsThere was a significant difference between dogs and cats in their ability to reach a post vaccination antibody titre of ≥ 0.5 IU/ml. Mice vaccinated with RABV-based rabies vaccines were partly cross-protected against EBLV-2, but there was no clear correlation between VNA titres and cross-protection against EBLV-2. Measurement of the RABV VNA titre can only be seen as a partial tool to estimate the cross-protection against other lyssaviruses. Booster vaccination is recommended for dogs and cats if exposed to infected bats.

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“…RABV vaccines are touted as one of the lowest cost but highest impact tradeoffs among vaccine-preventable infectious diseases (comparing procurement cost to Gavi, the Vaccine Alliance, and governments per death averted) ( Gavi, 2018 ). Critically, disease from other lyssaviruses is not always prevented by RABV-based vaccines and biologics: protection against phylogroup II and III viruses is minimal ( Weyer et al., 2008 ), and lapses in coverage by post-exposure prophylaxis (PEP) have even been shown within phylogroup I, despite phylogenic proximity to RABV ( Liu et al., 2013 ). Despite this, the available vaccines were developed solely against RABV ( Liu et al., 2013 ; Nel, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

Fisher¹,

Lowe²,

Smith³

et al. 2020

Cell Reports

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Summary Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV and MOKV Gs in mice. Immune sera also neutralize a range of wild-type lyssaviruses across the major phylogroups. LyssaVax-immunized mice are protected against challenge with recombinant RABV and MOKV. Altogether, LyssaVax demonstrates the utility of structural modeling in vaccine design and constitutes a broadened lyssavirus vaccine candidate.

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Evaluation of Rabies Biologics against Irkut Virus Isolated in China

Cited by 17 publications

References 25 publications

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against differentLyssavirusspecies

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against differentLyssavirusspecies

Efficacy of rabies vaccines in dogs and cats and protection in a mouse model against European bat lyssavirus type 2

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

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