Immune Response after Vaccination against Tick-Borne Encephalitis Virus (TBEV) in Horses

Abstract

(1) Background: Horses infected by a tick-borne encephalitis virus (TBEV) can develop clinically apparent infections. In humans, vaccination is the most effective preventive measure, while a vaccine is not available for horses. The objective of this study was to describe the immune response in horses after a TBEV vaccination with a human vaccine. (2) Materials and Methods: Seven healthy horses were randomised to a treatment or a control group in a stratified fashion based on TBEV-IgG concentrations on day -4. The treatment group (n = 4) was intramuscularly vaccinated using an inactivated human TBEV vaccine on days 0 and 28; the control group (n = 3) did not receive an injection. A clinical examination and blood sampling were performed on day -4, 0, 2, 4, 6, 8, 10, 14, 28, 30, 32, 34, 36, 38, 43, 56, 84, and 373. A linear mixed model analysis was used to compare IgG and IgM concentrations, neutralising antibody (nAb) titres, leucocyte count, serum amyloid A (SAA), and fibrinogen and globulin concentrations between the groups and time points. (3) Results: The clinical examination was normal in all horses at all time points. There were no significant changes in SAA, globulin, and fibrinogen concentrations and leucocyte count between the groups or time points (all p > 0.05). There was no significant increase in IgG, IgM, or nAb titres in the control group over time (all p > 0.05). In the vaccination group, there was a significant increase in IgG concentration and nAb titres after the second vaccination (p < 0.0001). There was no significant increase in IgM antibodies after the TBEV vaccination (all p > 0.05). One horse in the vaccination group had an IgM concentration above the laboratory reference on day 10. (4) Conclusions: The human TBEV vaccine did not have side effects when used in healthy horses in this study. A significant rise in TBEV-specific IgG antibodies and nAbs after the second vaccination was observed. However, IgG and nAb titres have been shown to decrease within 1 year after vaccination. The results of this study indicate that a vaccination with a human vaccine only induces a mild rise in IgM antibodies and only in previously naive horses. With no significant changes to inflammatory parameters in the vaccinated horses, it remains unclear whether vaccination with the human vaccine leads to protective immunity.

Keywords: IgG; IgM; SAA; TBEV; TBEV vaccination; equine; immune response; neutralising antibodies.

Figure 1

Overview of the study design of an experimental trial investigating the immune response to TBEV vaccination in horses. Days on which the horses were vaccinated (vaccinated group only, n = 4) and clinically examined (all study horses, n = 7), serum was sampled for IgG and an IgM ELISA and SNT (n = 7), and blood was taken for haematology and biochemistry (H and B, n = 7), which are indicated with an “X” in the respective row.

Figure 2

Longitudinal serum TBEV IgG concentration (VIEU/mL) after TBEV vaccination in 4 horses compared to 3 unvaccinated controls. IgG concentrations of horses in the vaccinated group (n = 4) are represented by green lines. IgG concentrations of the horses in the control group (n = 3) are represented by red lines. Time points of vaccinations are marked by stars. Values above the grey dotted line are seropositive (RI as per ELISA manufacturer: <63 seronegative, 63–126 borderline, >126 seropositive).

Figure 3

(a) Longitudinal serum nAb titres determined using SNTs after vaccination in four horses compared to three unvaccinated controls. Horses in the vaccinated group (V1–V4) are represented by green lines and horses in the control group (C1–C3) by red lines. Time points of vaccination are indicated with stars. Values above the grey dotted line are seropositive (LLOD: 1:16). (b) Longitudinal serum nAb titres after TBEV vaccination in four horses compared to three unvaccinated controls, values <50 only. Horses in the vaccinated group (V1–V4) are represented by green lines and horses in the control group (C1-C3) by red lines. Time points of vaccination are indicated with stars. Values above the grey dotted line are seropositive (LLOD: 1:16).

Figure 3

(a) Longitudinal serum nAb titres determined using SNTs after vaccination in four horses compared to three unvaccinated controls. Horses in the vaccinated group (V1–V4) are represented by green lines and horses in the control group (C1–C3) by red lines. Time points of vaccination are indicated with stars. Values above the grey dotted line are seropositive (LLOD: 1:16). (b) Longitudinal serum nAb titres after TBEV vaccination in four horses compared to three unvaccinated controls, values <50 only. Horses in the vaccinated group (V1–V4) are represented by green lines and horses in the control group (C1-C3) by red lines. Time points of vaccination are indicated with stars. Values above the grey dotted line are seropositive (LLOD: 1:16).

Figure 4

Longitudinal serum TBEV IgM concentration (LE) after TBEV vaccination in four horses compared to three unvaccinated controls. Horses in the vaccinated group (n = 4) are represented by green lines and horses in the control group (n = 3) by red lines. Time points of vaccination are indicated with stars. Values above the grey dotted line are seropositive (RI as per laboratory: <25 = seronegative; >25 = seropositive).