Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid.IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV. KEYWORDS B cell, FMDV, T-independent, viral immunology F oot-and-mouth disease virus (FMDV) is a highly contagious pathogen that has a large socioeconomic impact upon countries in which the virus is endemic. Studies of cattle and mice have shown that protection from the virus is largely mediated by antibodies (1). One of the main approaches to FMD control is through vaccination with inactivated FMDV antigen in formulation with adjuvants (2). However, the current inactivated FMDV vaccines are unable to induce long duration of immunity in cattle; regular repeated immunizations are required to maintain protective antibody titers (1).It is generally considered that serological protection against one FMDV serotype does not confer interserotype protection and may not, in some cases, confer intraserotype protection, given the antigenic variation seen within some serotypes (1). We have recently shown that intraserotype protection is possible within the FMDV O serotype using a heterologous FMDV challenge model following a single vaccination with inactivated FMDV (3). Indeed, Cottral and Gailiunas were able to demonstrate that after three rounds of challenge with multiple FMDV serotypes, the animals were resistant to further FMDV challenges (4). These animals had clearly developed cross-

Section: Discussionsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes

Grant

Carr

Kotecha

et al. 2017

“…We incorrectly anticipated that high neutralizing antibody titers at these time points would hinder recovery (49). Similarly, FMDV has successfully been isolated from lymphoid tissues from carrier sheep and cattle (50,51).…”

Section: Discussionmentioning

confidence: 99%

Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence

Maree

Klerk-Lorist²,

Gubbins

et al. 2016

104

d ABSTRACTFoot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCEFoot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem.

“…Virulent FMDV strain O1/Campos/Brazil/58 (O1 Campos) was provided by the OIE FMD Reference Laboratory at SENASA, Argentina. Experimental infections through the oronasal route were performed with a jet nebulizer attached to an aerosol delivery system (10 7 50% tissue culture infective doses [TCID 50 ] in a 2-ml volume per animal) as previously reported (20,22). After infection, animals were monitored daily for clinical signs of FMD.…”

Section: Methodsmentioning

confidence: 99%

“…Following our previous study on the induction of local adaptive responses in naive bovines infected through the oronasal route (20), here we analyzed the local antibody production induced after systemic FMD vaccination and the responses triggered in these animals after oronasal challenge with virulent FMDV. Our results demonstrate that soon after systemic immunization with high-payload FMD vaccines, it is possible to detect virusspecific antibody-secreting cells (ASC) in lymphoid tissues distal from the inoculation spot.…”

mentioning

confidence: 99%

Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection

Pega

Giacomo

Bucafusco

et al. 2015

Self Cite

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n ‫؍‬ 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virusspecific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. F oot-and-mouth disease (FMD) is a highly contagious and acute viral disease affecting a wide range of economically important livestock species (1). All domestic biungulates are susceptible to infection with the FMD virus (FMDV); in addition, a number of wildlife species may act as reservoirs for the virus under particular ecological conditions (2). Lethality has been described for young animals and certain FMDV strains (3). However, the main disruptive potential of this transboundary disease is the high morbidity rate and the numerous indirect losses associated with its incursions into territories with susceptible populations. Consequently, FMD outbreaks may result in severe and far-reaching economic losses due to the interruption of regional and international trade in developed countries (4, 5), but also importantly, due to the loss of animals, production efficiency, and genetic diversity in developing regions (6).Cattle are highly susceptible to FMDV, and virus usually gains entry through the respiratory tract of the animals (3). The soft palate and pharynx were identified as primary sites of FMDV replication and persistence in bovines infected through the oronasal route (7,8). FMDV infection progresses through replication in pneumocytes, permitting the virus to accomplish an extensi...