Clin Exp Vaccine Res.  2017 Jul;6(2):128-134. 10.7774/cevr.2017.6.2.128.

A genetically modified rabies vaccine (ERAGS) induces protective immunity in dogs and cattle

• Yang DK
• Kim HH
• Lee SH
• Jeong WH
• Tark D
• Cho IS

• KMID: 2391573
• DOI: http://doi.org/10.7774/cevr.2017.6.2.128

Abstract

PURPOSE
The current live attenuated rabies vaccine must be replaced with a safer vaccine based on the ERAGS strain to prevent rabies in South Korea. We evaluated the safety and immunogenicity of a new strain in dogs and cattle.
MATERIALS AND METHODS
The ERAGS strain, featuring two mutations altering two amino acids in a glycoprotein of rabies virus, was propagated in NG108-15 cells. We lyophilized the virus in the presence of two different stabilizers to evaluate the utilities of such preparations as novel rabies vaccines for animals. To explore safety and immunogenicity, dogs and cattle were inoculated with the vaccine at various doses via different routes and observed daily for 8 weeks post-inoculation (WPI). Immunogenicity was evaluated using a fluorescent antibody virus neutralization test or enzyme-linked immunosorbent assay.
RESULTS
The two different stabilizers did not differ greatly in terms of maintenance of virus viability in accelerated stability testing. No clinical signs of rabies developed in dogs or cattle inoculated with the vaccines (10(7.0) FAIDâ‚…â‚€/mL). Dogs and cattle inoculated intramuscularly with 10(5.0) FAIDâ‚…â‚€/mL exhibited virus neutralization assay titers of 4.6 IU/mL and 1.5 to 0.87 IU/mL at 4 WPI, respectively. All control animals remained rabies virus-seronegative throughout, confirming that no contact transmission occurred between vaccinated and control animals.
CONCLUSION
Our findings indicate that the new rabies vaccine is safe and immunogenic in dogs and cattle.

Keyword

Rabies; Vaccines; Dogs; Cattle

MeSH Terms

Amino Acids
Animals
Cattle*
Dogs*
Enzyme-Linked Immunosorbent Assay
Glycoproteins
Korea
Microbial Viability
Neutralization Tests
Rabies Vaccines*
Rabies virus
Rabies*
Vaccines
Amino Acids
Glycoproteins
Rabies Vaccines
Vaccines

Figure

• 

  Fig. 1 Accelerated stability testing of the freeze-dried rabies vaccine at various temperatures (4℃, 24℃, and 37℃). Virus was prepared with two types of stabilizer (LPGG or TPGG), and viral titers in NG108-15 cells were measured at the times shown. LPGG, lactose/phosphate/glutamate/gelatin; TPGG, trehalose/phosphate/glutamate/gelatin.

• 

  Fig. 2 The immune response of dogs inoculated dose-dependently with the ERAGS strain via the intramuscular (IM) (A and C) and subcutaneous (SC) (B and D) routes. The fluorescent assay virus neutralization and enzyme-linked immunosorbent assay titers of the sera were measured. Dogs inoculated with >103.0 FAID50/mL vaccine via the IM route exhibited protective immune responses by 4 weeks post-inoculation (WPI). Each bar represents the mean±standard deviation from four independent samples. NC, negative control. Different lower-case letters above the bars indicate significant differences among groups (p<0.05, Tukey's post-hoc test).

• 

  Fig. 3 Immune responses in cattle given vaccine via the intramuscular (IM) route. Antibody titers were measured using the fluorescent assay virus neutralization (FAVN) test. Cattle inoculated with >104.0 FAID50/mL vaccine developed protective levels (0.81 IU/mL) of anti-rabies antibodies. NC, negative control; WPI, weeks post-inoculation. Different lower-case letters above the bars indicate significant differences among groups (p<0.05, Tukey's post hoc test).

• 

  Fig. 4 Comparison of virus-neutralizing antibody titers in animals given 105.0 FAID50/mL vaccine via different inoculation routes (A). Comparison of data between the two animal species (B). FAVN, fluorescent assay virus neutralization. *Significant difference between the intramuscular (IM) and subcutaneous (SC) routes or between dogs and cattle (p<0.05, paired Student's t test).

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