Toward the calibration of serological assays using sera collected from cattle and sheep following a single dose of foot-and-mouth disease vaccine

Abstract

Background and aim: Serological assays are widely used to monitor the performance of foot-and-mouth disease (FMD) vaccines to estimate vaccination coverage and to ensure that vaccinated animals generate adequate immune responses. This study aimed to measure the FMD virus (FMDV)-specific responses in cattle and sheep after a single dose of a trivalent FMD vaccine containing serotypes A, O, and Asia-1, and to use these sera to calibrate virus neutralization tests (VNTs) and serotype-specific serological enzyme-linked immunoassays (ELISAs) that can measure post-vaccination responses.

Materials and methods: Sera were collected from cattle (n=10) and sheep (n=10) on 0, 21, and 56 days after immunization with an imported aqueous formulated FMD vaccine. These samples were tested by VNT using field FMDV isolates that are representative of the epidemiological risks in Central Asia (A/ASIA/Iran-05, A/ASIA/GVII, O/ME-SA/Ind-2001, O/SEA/Mya-98, O/ME-SA/PanAsia, and Asia-1 Shamir). Heterologous VNT antibody responses were compared to those measured using commercial FMDV-specific ELISAs for serotypes O, A, and Asia 1.

Results: Administration of the FMD vaccine increased FMDV-specific antibody titers for both species in sera collected on day 21, but these elevated titers were short-lived and were decreased by day 56.

Conclusion: These results highlight the short duration of immunity with a single dose of this aqueous vaccine and motivate further studies to assess immune responses in cattle and small ruminants after a two-dose course vaccination schedule. Further comparative data for VNT and serotype-specific ELISAs are needed to define cutoffs that can be used to monitor post-vaccination immune responses in low-containment laboratories where it is not possible to handle live FMDVs.

Keywords: cattle; enzyme-linked immunoassay; foot-and-mouth disease; immunogenicity; post-vaccination monitoring; sheep; virus neutralization test.

Figure-1

Current foot-and-mouth disease (FMD) zones for Kazakhstan. Dark green areas represent FMD-free zones where vaccination is not practiced and light green areas are areas that are FMD-free zones where vaccination is practiced [Source: https://www.oie.int/en/disease/foot-and-mouth-disease/#ui-id-2].

Figure-2

Post-vaccination heterologous virus neutralization test (VNT) responses in naïve cattle (•) and sheep (○) after a single dose of foot-and-mouth disease (FMD) vaccine. Data shown represent mean±standard deviation titers measured at three time points during the study with six different regional FMD virus reference antigens. Shaded boxes denote negative (dark gray: <1/11 titer) and inconclusive (light gray; >1/11 to <1/32 titer) VNT results.

Figure-3

Pairwise comparison between enzyme-linked immunoassay (ELISA) responses (PrioCHECK) and heterologous virus neutralization test titers measured against six regional foot-and-mouth disease virus reference antigens. Gray areas denote negative ELISA values that are below the 50% inhibition cutoff for these tests.

Figure-4

(a) Pairwise comparison between enzyme-linked immunoassay (ELISA) responses (Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna) and heterologous virus neutralization test titers measured against six regional foot-and-mouth disease virus reference antigens. Gray areas denote negative ELISA values that are below the 70% inhibition cutoff for these tests. Calculated antibody titers for serotypes A and Asia 1 are shown in B.