Evaluation of a non-invasive, inhalational challenge method for rabies vaccine potency assay

Lewis, Charles E.; Reising, Monica M.; Fry, Alethea M.; Conrad, S.K.; Siev, David; Gatewood, Donna M.; Hermann, Joseph

doi:10.1016/j.jviromet.2013.03.020

Cited by 5 publications

(5 citation statements)

References 13 publications

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“…Half of the mice that were actively immunized with (inactivated) vaccine, both at 28 and 25 days before challenge, still developed lethal brain infection. This incomplete protection, even with high antigenic doses (2 x 0.25 AU/mouse), is also described by other researchers, using similar models [ 18 ]. Nevertheless, the applied vaccine schedule resulted in clear seroconversion of all mice, with virus-neutralizing serum titers well above the protective threshold of 0.5 IU/ml (range 6.01–18.04 IU/ml) at the moment of challenge.…”

Section: Discussionsupporting

confidence: 80%

“…First disease signs appear at 7 days, which rapidly progress the following 2 days, requiring euthanasia at 8–9 days post inoculation (DPI). This model was recently also proposed as a valuable alternative to intracranial inoculation for rabies vaccine potency testing [ 18 ]. The typically short incubation period of this model (6.07 ± 0.59 days) is ideal to study the potentially beneficial effect of the combined passive (VHH) and active (vaccine) immunisation on disease outcome.…”

Section: Introductionmentioning

confidence: 99%

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Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

et al. 2016

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Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

et al. 2016

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“…Rabies is fatal zoonotic viral disease. Rabies virus is a neurotropic, negative sense, single-stranded RNA virus that belongs to the family Rhabdoviridae, genus Lyssavirus [1]. The causative virus can spread from saliva of infected animals to others through neuromuscular route [2].…”

Section: Introductionmentioning

confidence: 99%

Serological profiling of rabies antibodies by enzyme-linked immunosorbent assay and its comparative analysis with rapid fluorescent focus inhibition test in mouse model

et al. 2019

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Aim: In this study, we have used enzyme-linked immunosorbent assay (ELISA) as an alternative test to replace the cumbersome rapid fluorescent focus inhibition test (RFFIT) to ascertain the immune status of immunized mice against rabies virus. Materials and Methods: Rabies is a devastating disease worldwide caused by rabies virus. Proper usage of pre- or post-exposure rabies vaccine can prevent the disease transmission. In this study, mice were immunized with Vero cell-adapted inactivated rabies vaccine. RFFIT was used as a test to determine the serum neutralizing titers in infected/vaccinated mice. Seroprofiling of mice sera was done in vitro by ELISA. Results: Twenty-one days post-immunization, both ELISA and RFFIT assays indicated similar antibody levels in mice sera that were immunized with Vero cell-adapted inactivated rabies vaccine. Both the tests were correlated, and the linearity was verified by the regression line (R2=0.979). Conclusion: In this study, we profiled the serological status of Vero cell-adapted inactivated rabies vaccine through ELISA in mice model that correlated well with the OIE gold standard test RFFIT.

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“…Third, the i.n. route has been shown to be an acceptable alternative to intracranial injection for RABV challenge ( Lafay et al., 1991 ; Lewis et al., 2013 ; Rosseels et al., 2011 ). Finally, i.n.…”

Section: Discussionmentioning

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 a non-invasive, inhalational challenge method for rabies vaccine potency assay

Cited by 5 publications

References 13 publications

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection

Serological profiling of rabies antibodies by enzyme-linked immunosorbent assay and its comparative analysis with rapid fluorescent focus inhibition test in mouse model

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

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