Foot-and-mouth disease (FMD) is one of the most important animal diseases. FMD is highly contagious to cloven-hoofed animals and causes severe economic losses due to its devastating impact on trade and reduced animal productivity (1). The causative agent is the foot-and-mouth disease virus (FMDV), which belongs to the genus Aphthovirus of the family Picornaviridae. FMDV is divided into seven genetically and immunologically distinct serotypes [O, A, Asia 1, C, Southern African Territories (SAT) 1, SAT 2 and SAT 3] including multiple topotypes and genetic lineages (2, 3). FMDV strains circulating throughout the world have been geographically divided into seven regional virus pools (1, 4). Serotype O, A, and Asia 1 viruses circulate in the Asian pools (Pools 1, 2, and 3), which pose threats to livestock industries in countries such as the Republic of Korea.

Serotype O is the most widely distributed of the seven FMDV serotypes. In Southeast Asia and East Asia (Pool 1), serotype O viruses are responsible for over 80% of the officially reported outbreaks. Type O viruses belonging to the SEA (O/SEA/Mya-98), ME-SA (O/ME-SA/PanAsia, O/ME-SA/Ind-2001) and CATHAY topotypes are endemic in this region. The O/ME-SA/Ind-2001 lineage has been classified into five sublineages, namely, a, b, c, d, and e. Since 2020, there has been an upward trend in the dominance of the O/Ind-2001e sublineage in Southeast Asian countries (5).

The Republic of Korea was free from FMD from 1934 until 2000. However, since 2000, FMD has been introduced into the country on multiple occasions. FMD outbreaks in 2010 caused significant economic damage estimated at more than US$ 3.6 billion (6). As a consequence, a national program that ensured that all FMD-susceptible animals were vaccinated began in early 2011. However, despite this strong nationwide vaccination policies, FMD recurred every year from 2014 to 2019, recording a total of 11 incursions since 2000 caused by both FMD type O and A viruses (7, 8). The genotypes of FMDV that have been detected in the Republic of Korea are O/ME-SA/PanAsia, O/ME-SA/Ind-2001e, O/SEA/Mya-98 and A/ASIA/Sea-97. During 9 days in May 2023, new FMD clinical cases were reported on ten cattle and one goat farms located in two regions, Cheongju and Jeungpyeong of Chungbuk. The FMD-reported animals showed typical clinical signs and lesions, such as anorexia, vesicular fluids, erosion, and drooling. In this study, genetic characterization of the causative virus and vaccine matching test using a virus isolated from clinical samples were conducted to investigate (i) the epidemiological relationship with contemporary FMD viruses circulating in neighboring regions, and (ii) the antigenic relatedness of commercial vaccine strains used for domestic compulsory vaccination. These data help to understand the risk pathways by which FMDVs enter the Republic of Korea and provide data to support the national vaccination control strategy.

There had been no FMD outbreaks detected in livestock of the Republic of Korea after the 11th FMD incursion reported in Anseong during January 2019. In the recent outbreaks of May 2023, a lateral flow device was used to rapidly detect FMDV in samples collected from animals exhibiting FMD clinical signs. Further testing using 3D and VP1 real-time RT-PCR confirmed FMD and serotype of FMDV, and sequencing of VP1 coding region revealed that the FMDV strain introduced into the Republic of Korea belonged to O/ME-SA/Ind-2001e sub-lineage. A national livestock standstill with culling and disinfection of the infected farms was implemented. Furthermore, emergency vaccination was conducted for all FMD-susceptible animals nationwide. These measures have been successful since no further FMD-suspected case has been identified since the last case reported the 18th of May 2023.

The thorough national epidemiological investigation suggested FMDV introduction possibly from neighboring countries via illegal animal products, based on the following assumptions: (i) for the past 4 years after the last FMD outbreak of 2019, a strict FMD reporting system and a post-vaccination monitoring (PVM) program involving 1.2 millions of animals have been implemented for all FMDV susceptible livestock in the country; these systems have not detected any FMD-suspected cases nor evidence of FMDV infection from non-negative NSP-positive animals identified during surveillance; finding which were confirmed by real-time RT-PCR testing of clinical samples of the NSP-non-negative animals as well as other animals from these farms; (ii) FMDV and 5 antibody test using antisera (n = 8,681) of wild animals (wild boar, water deer, roe deer, etc.) during the last 5 years from 2019 to June 2023 showed no FMDV infection in wild animal populations of the Republic of Korea (data not shown); (iii) the FMDV isolates genetically characterized from the 2023 outbreak belonged to the O/ME-SA/Ind-2001e, clustering in a phylogenetic group that was distinct from those viruses of the same lineage that caused the outbreaks reported in 2017 and 2019, with 5–6% of nucleotide difference in the FMDV sequences of the VP1 coding region. From the phylogenetic tree, the 2023 FMD viruses were closely related to field viruses (O/ME-SA/Ind-2001e) isolated between 2022 and 2021 from Mongolia and other Southeast Asian countries (Laos, Vietnam, and Cambodia) with ~1% of nucleotide sequence difference, clustering within the same group. This FMDV lineage, is the predominant strain circulating within FMD endemic Pool 1, as was reported during 2020-2023 (19, 20); (iv) Inspections of illegal livestock products found about 60 cases/day in the luggage of travelers visiting neighboring countries and about 70 cases/day in overseas express cargo. In addition, inspections of foreign grocery stores in cities and counties adjacent to the FMD outbreak areas confirmed the illegal sale of animal products.

It was confirmed by vaccine-matching tests that type O FMDV strains of the commercial vaccines used for compulsory systemic vaccination policy in the Republic of Korea were well matched (r1 value >0.3) against the FMD field isolates (Table 3), including those FMDV isolates causing outbreaks in 2017 and 2019. Therefore, it is believed that the emergency vaccination should be highly effective to contain the FMD outbreaks within limited areas (two regions in a province) for a short period of time (9 days), as demonstrated in swift control of FMD outbreaks during the past two outbreaks (2017 and 2019) reported in the Republic of Korea. The effect of emergency vaccination as one of major control measures in emergency FMD outbreaks (18, 21) was already proven by previous studies (22).

During the nationwide vaccination policy, post-vaccination monitoring (PVM) showed that over 90% of FMD-susceptible livestock had seroconverted (23), satisfying 80% population herd immunity on average, which was also confirmed in the recent PVM carried out between January and June of 2023 (data not shown). Nevertheless, the likely cause of FMDV introduction and transmission within a systematically vaccinated population might be occur if the levels of protective immunity are low as observed on some farms. As shown in a previous study (23), around 0.3–0.79% of farms were found to have less than 80% of herd immunity, despite the effective vaccination policy, with presence of livestock farms having low herd immunity was still observed during the recent PVM carried out in 2023. In general, the level of herd immunity depends on the reproduction ratio (R₀) as well as effectiveness of vaccination. 75–80% coverage of population herd immunity is usually referenced as the level of immunity required to block the spread of FMDV (24, 25), when R₀ of an FMD outbreak is estimated to be below 5 and vaccination is 100% effective (26). SP/O ELISA was conducted in all the 11 farms reported of being infected by FMD in Chungbuk Province, where results revealed a positive rate between 24 and 75% for 7 farms (data not shown). Understanding these results is important because even if the vaccine is well matched and high potency, any non-compliance with vaccination procedures prescribed by manufacturer or the Republic of Korea Government guidelines may lead to immunity gaps on farms. Testing of samples from the remaining four FMD-positive farms revealed over 80% SP/O ELISA positive rate, which might be results of anamnestic responses induced by viral infection following vaccination.

After a period of 4 years where no FMD outbreaks have been detected, this report highlights the reintroduction of the O/ME-SA/Ind-2001e FMDV lineage into the Republic of Korea during May of 2023. The active circulation of this lineage in neighboring countries suggest a transboundary origin for these cases, which was further supported by the close genetic relatedness between the field viruses of the same FMDV lineage isolated from other East Asian countries between 2021 and 2022. It was noted that the outbreaks occurred on farms with a low level of serotype O-specific antibodies despite the systemic compulsory vaccination policy. These findings reinforce the importance of maintaining the protective immune status against FMDV to prevent the occurrence of FMD in geographic situations where FMDV may be introduced.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number (s) can be found in the article/supplementary material.

Ethical approval was not required for the study involving animals in accordance with the local legislation and institutional requirements because No ethical approval was required for this study as sample collection was performed using standard diagnostic procedures with no harm to the animals. Written informed consent was obtained from the owners for the participation of their animals in this study.

SR: Conceptualization, Data curation, Formal analysis, Visualization, Writing – original draft, Writing – review & editing. HK: Data curation, Formal analysis, Visualization, Writing – original draft, Writing – review & editing. D-RL: Data curation, Formal analysis, Visualization, Writing – original draft. J-MK: Project administration, Writing – review & editing. YW: Investigation, Writing – review & editing. JK: Investigation, Writing – review & editing. DK: Data curation, Formal analysis, Writing – review & editing. AN: Writing – review & editing, Data curation, Formal analysis. S-HC: Conceptualization, Data curation, Formal analysis, Supervision, Writing – original draft, Writing – review & editing.