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The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4⁺ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer.

ABSTRACT: Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4⁺ T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4⁺ T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported; two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-γ in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4⁺ T cells exhibited the highest frequency amongst the identified epitopes, comprising >0·004% of the CD4⁺ T-cell population. CD45RO⁺ CCR7⁺ defined central memory CD4⁺ T-cell subpopulations were present in higher frequency in FMDV-specific CD4⁺ T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4⁺ T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.

SUBMITTER: Mitoma S

PROVIDER: S-EPMC8442236 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicle-associated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+/MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+/CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of epithelial cells of the nasopharyngeal mucosa that could enable shedding and long-term persistence of infectious virus. Additionally, these data indicate different mechanisms within the immediate host response to infection between non-vaccinated and vaccinated cattle.

Project description:Development of a foot-and-mouth disease (FMD) carrier state following FMD virus (FMDV) infection is a well-established phenomenon in cattle. However, the proportion of cattle likely to become carriers and the duration of the carrier state at a herd or population-level are incompletely understood. The objective of this study was to examine the epidemiologic and economic impacts of vaccination-to-live strategy in a disease-free region or country. We developed and simulated scenarios of FMD spread and control in the US livestock population, which included depopulation for a limited period, followed by a vaccinate-to-live strategy with strong biosecurity and movement restrictions. Six scenarios of FMD spread and control were simulated in the InterSpread Plus (ISP) modeling tool. Data on the number of infected and depopulated cattle (by operation types) from ISP model runs were used to estimate the monthly number of infected but not depopulated (potential carrier) cattle after the infection. Using available literature data on the FMD carrier state, we estimated the monthly proportion of carrier cattle (from infected but not depopulated cattle) over time following infection. Among the simulated scenarios, the median (25th, 75th percentile) number of infected cattle ranged from 43,217 (42,819, 55,274) head to 148,907 (75,819, 205,350) head, and the epidemic duration ranged from 20 (11, 30) to 76 (38, 136) days. In general, larger outbreaks occurred when depopulation was carried out through longer periods, and the onset of the vaccination was late (p > 0.05). The estimated proportion of surviving cattle, which were infected and not depopulated and had the potential to become persistently infected ranged from 14 to 35% of total infected cattle. Production losses in beef and dairy sectors were higher when outbreaks started in multiple states simultaneously, but production losses were small compared to trade losses and consumer avoidance losses. These results can be used to inform the consideration of a vaccinate-to-live strategy for FMD outbreaks and the development of appropriate post-outbreak management strategies. Furthermore, this output will enable a more detailed examination of the epidemiologic and economic implications of allowing convalescent cattle to survive and remain in production chains after FMD outbreaks in FMD-free regions.

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The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4⁺ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer.

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The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4+ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer.

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OmicsDI is part of the ELIXIR infrastructure

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The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4⁺ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer.