Application of Serological Tests to Assess the
Efficacy of Foot-and-Mouth Disease Vaccination
in Dairy Cattle with or without Viral Leucosis
Alejandra V Capozzo*
Instituto Nacional de Tecnologia Agropecuaria, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Submission: November 19, 2018;Published: December 03, 2018
*Corresponding author: Alejandra V Capozzo, Instituto Nacional de Tecnologia Agropecuaria, Instituto de Virología, Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
How to cite this article: Alejandra V C. Application of Serological Tests to Assess the Efficacy of Foot-and-Mouth Disease Vaccination in Dairy Cattle with
or Without Viral Leucosis. Dairy and Vet Sci J. 2018; 8(3): 555738. DOI: 10.19080/JDVS.2018.08.555738
Enzootic bovine leucosis is an infectious viral disease of cattle distributed worldwide that affect dairy cattle over 2 years of age. This disease produces changes in the animal´s immune system that may affect vaccine efficacy. During the last 10 years many reports have highlighted the association of BLV infection with a diminished or modified immune response against routinely used cattle vaccines. Our group has focused on studying the possible role of BLV infection on the immune response elicited by foot-and-mouth disease primo or multiple vaccinations making use of serological assays aimed to characterize the antibody response in terms of IgG-subtypes and avidity. These tools demonstrated to be very useful for analyzing the effects of BLV in FMD vaccine immunity. The use of simple high-throughput assays delving on the quality of the antibody response is paramount for assessing vaccine efficacy and can help in analyzing the impact of BLV infection at herd level.
Enzootic bovine leucosis is an infectious disease of cattle induced by bovine leukemia virus (BLV). This retrovirus is worldwide distributed, and all cattle breeds are susceptible, although the incidence is higher in dairy cows and in animals over 2 years of age and increases with age . Approximately sixty percent of infected animals do not display clinical signs of disease, and these animals are referred to as asymptomatic or aleukemic. Approximately 30–40% of BLV carriers will develop a persistent lymphocytosis, while fewer than 5% develop malignant lymphosarcoma . The disease is difficult to control, and only a few countries have been able to eradicate the disease.
BLV infection impedes the normal function of the immune system, affecting cells of the innate and adaptive immunity . A study performed in 1989 reported a possible impairment of the immune response against rotavirus in BLV-infected animals . Considering that BLV is endemic in many countries and approximately 60% of the animals are asymptomatic, it is important to know how BLV infection impacts the immunogenicity of vaccines compulsory applied to cattle populations. Despite strong evidence of abnormal immune signalling and functioning, little research has investigated the large-scale effects of BLV infection on host immunity and resistance to other infectious diseases. Work performed along the last 10 years have shown that that BLV positive (by serology) dairy cows exhibit a decreased or modified
immune response against primo-vaccination to a bacteria or inactivated virus-vaccine as compared to non-infected cows [5-8].
A compromised immune response to vaccination will be particularly detrimental for foot and mouth disease (FMD) control. FMD is endemic in many parts of Asia, Africa, and South America, where vaccination of susceptible populations is compulsory used as the major tool to prevent outbreaks of this extremely contagious virus. FMD has global consequences, costing an estimated USD $6–$21 billion each year in prevention expenditures and agricultural damage. A significant portion of this cost is undertaken by low- and middle-income countries that suffer huge economic losses from trade restrictions, both of animals and derived products [9,10].
Commercial vaccine formulations used in FMD vaccination campaigns are based on BEI-inactivated viral particles, and usually contain more than one virus strain, as immune responses induced by vaccination are not cross-protective between strains . Protection against FMDV has been related to antibody levels induced by vaccination . High levels of serum neutralizing antibodies and particularly, IgG1 levels are related to protection in vaccinated cattle [13,14]. Maintaining high levels of total antibodies against FMDV is paramount to prevent outbreaks. The well-characterized immune response elicited against FMDV using the current commercial vaccines allowed the analysis of the effect of BLV on the immune response elicited by FMD vaccine.
FMD vaccination represents then an excellent model to study the effect of BLV in the development of immunity. FMD vaccines are well-controlled in many South-American countries. In Argentina,
vaccination campaigns are applied under the supervision of the
national authorities, certifying cold chain and correct application.
Another advantage is the availability of ELISAs that allow a precise
correlation with that can be used to study FMD-vaccine efficacy
in the field [15,16]. Apart from assays measuring total antibodies,
like liquid phase blocking ELISA used since the late eighties
, there are also simple high-throughput serological tools to
characterize the quality of the antibody response .
The quality of vaccine-induced antibodies, defined by isotype
profile and avidity, has been identified as a defining factor in
efficacy. FMDV isotype ELISAs for cattle sera were developed in
the nineties . They are indirect tests used to titrate anti FMDV
IgG1 and IgG2 in sera. The rate between IgG1 and IgG2 titers has
been related to protection against FMDV specially when studying
cross- protection [14,18]. Isotypes bring information of the type
of immune response, if it is related to antibody-mediated cellular
responses or if they are mainly neutralizing responses. Avidity is
another parameter of the “functional affinity” of specific antibodies.
It is related to the interaction between polyclonal antibodies
in a sample and the bound antigen. Avidity is influenced by the
antibody serotype, their epitope-paratope affinity, the number
of antibodies and their aminoacidic sequence. When vaccines
stimulate the acquired immunity, antigen-specific B cells undergo
somatic hypermutation and affinity-based selection, resulting in B
cells that produce antibodies with increased avidity over germline
antibodies. Avidity can be considered a landmark of efficient
vaccination  and has been related to protection for many
vaccines and diseases , used to discriminate between chronic
and acute infections  and correlated to capacity of antibodies
to neutralize viral infection in cultured cells [20,22].
Analysis of the isotypes of the antibodies induced against a virus
strain in primo-vaccinated cattle revealed that IgM, IgG1 and
IgG2 titres increased in both positive (BLV+) and negative (BLV-)
heifers following FMD immunization, although IgM and IgG1 titters
were higher in non-infected animals . Levels of IgG2 can
explain why the difference in antibody titters was only marginally
significant when total antibodies were measured. The avidity
index was lower in seropositive animals than that seronegative,
meaning a reduced capacity of developing a protective immune
response. These results demonstrated that BLV infection in dairy
cattle modified the profile of antibody response to FMD primo-
vaccination, biasing the isotype switch towards IgG2 though
total antibody levels were marginally affected. These differences
may be caused by the cytokine modulation exerted by BLV.
In a larger study  we measured anti FMDV antibodies
from two-hundred milking cows (>2 years old) selected based on
their BLV-serologic status (100 BLV+ and 100 BLV-). The animals
were in two large farms in Argentina (500 animals each), one
with low and another with high BLV prevalence. The aim of this
study was to investigate if BLV-status could interfere with the
efficacy of the FMDV-vaccination campaign. This is of interest
in FMDV-endemic regions since the total FMDV-antibody titers
induced through vaccination are necessary to prevent disease
outbreaks. Here we showed that after repeated vaccination, levels
and avidity of anti-FMDV antibodies were similar between BLV +
and BLV- animals. Although primo-vaccination may be affected
, repeated vaccination probably weakens this effect at a herd
level, as animals may get infected with BLV at different times
before or after their primo-vaccination. The use of avidity in this
study allowed detecting individual vaccine failures that cannot
be accounted by just measuring total antibodies. Our results
suggested that BLV-status did not compromise the efficacy of
routine FMDV-vaccination in cattle.
The use of serological high-throughput assays allowed to study
if FMD vaccination was affected by the animal´s BLV serological
status. These simple tools were useful to characterize the immune
response at individual level and get a closer insight on the effects
of this important viral disease of dairy cattle, revealing individual
vaccine failures and helping to better characterizing the effect of
BLV infection on the immune response induced by vaccination, at
a herd level. These serological assays constitute important tools to
assess vaccine performance in the field.