Heterologous Prime-Boost Vaccination with Commercial FMD Vaccines Elicits a Broader Immune Response than Homologous Prime-Boost Vaccination in Pigs

Abstract

Three commercial vaccines are administered in domestic livestock farms for routine vaccination to aid for foot-and-mouth disease (FMD) control in Korea. Each vaccine contains distinct combinations of inactivated serotype O and A FMD virus (FMDV) antigens: O/Manisa + O/3039 + A/Iraq formulated in a double oil emulsion (DOE), O/Primorsky + A/Zabaikalsky formulated in a DOE, and O/Campos + A/Cruzeiro + A/2001 formulated in a single oil emulsion. Despite the recommendation for a prime-boost vaccination with the same vaccine in fattening pigs, occasional cross-inoculation is inevitable for many reasons, such as lack of compliance with vaccination guidelines, erroneous application, or change in vaccine types by suppliers. Therefore, there have been concerns that a poor immune response could be induced by cross-inoculation due to a failure to boost the immune response. In the present study, it was demonstrated by virus neutralization and ELISA tests that cross-inoculation of pigs with three commercial FMD vaccines does not hamper the immune response against the primary vaccine strains and enhances broader cross-reactivity against heterologous vaccine antigens whether they were applied or not. Therefore, it could be concluded that the cross-inoculation of FMD vaccines can be used as a regimen to strategically overcome the limitation of the antigenic spectrum induced by the original regimen.

Keywords: cross-inoculation; foot-and-mouth disease virus; heterologous prime-boost; homologous prime-boost; serological performance.

Figure 1

Phylogenetic tree showing the genetic relationships of FMDV type O vaccine strains and other isolates. Genetic distances were calculated with the Kimura two-parameter method based on the complete sequence of the VP1-coding region. A maximum likelihood tree was built using MEGA, version 11.0. The scale bar indicates nucleotide substitutions per site. Relevant lineages and topotypes are indicated with brackets. Black circles indicate the original reference viruses of vaccine strains. Black triangles indicate the Korean type O isolates since 2000.

Figure 2

Phylogenetic tree showing the genetic relationships of FMDV type A vaccine strains and Korean isolates. Genetic distances were calculated with the Kimura two-parameter method based on the complete sequence of the VP1-coding region. A maximum likelihood tree was built using MEGA, version 11.0. The scale bar indicates nucleotide substitutions per site. Relevant lineages and topotypes are indicated with brackets. Black circles indicate the original reference viruses of type A vaccine strains used in Korea. Black triangles indicate the Korean type A isolates since 2010.

Figure 3

The type O FMDV-neutralizing antibody responses detected in serum samples from the farm-resident pigs of each group (n = 22), which were vaccinated with FMD vaccines. Blood was collected at 1 week before primary vaccination at 8 weeks of age and 4, 8, 16, 20, and 24 weeks after primary vaccination. Primary and booster vaccination were applied at 8 and 12 weeks of age, respectively. Nine groups were allocated according to the vaccine used: three homologous booster vaccination groups in which A-A, B-B, and C-C regimens were employed, and six heterologous booster vaccination groups in which A-B, A-C, B-A, B-C, C-A, and C-B regimens were employed. The results of the groups primed with O/Manisa + O/3039 + A/Iraq are depicted in (A,D,G,J). The results of the groups primed with O/Primorsky+A/Zabaikalsky are depicted in (B,E,H,K). The results of the groups primed with O/Campos + A/Cruzeiro + A/2001 are depicted in (C,F,I,L). The antigens used in the VN titer test are indicated at the top-center of each graph. Error bars represent the SEMs. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 4

The type A FMDV-neutralizing antibody responses detected in serum samples from the farm-resident pigs of each group (n = 22), which were vaccinated with FMD vaccines. Blood was collected at 1 week before primary vaccination and 4, 8, 16, 20, and 24 weeks after primary vaccination. Primary and booster vaccination were applied at 8 and 12 weeks of age, respectively. Nine groups were allocated according to the vaccine used: three homologous booster vaccination groups in which A-A, B-B, and C-C regimens were applied, and six heterologous booster vaccination groups in which A-B, A-C, B-A, B-C, C-A, and C-B regimens were applied. The results of the groups primed with O/Manisa + O/3039 + A/Iraq are depicted in (A,D,G,J). The results of the groups primed with O/Primorsky+A/Zabaikalsky are depicted in (B,E,H,K). The results of the groups primed with O/Campos + A/Cruzeiro + A/2001 are depicted in (C,F,I,L). The antigens used in VN titer test are indicated at the top-center of each graph. Error bars represent the SEMs. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 5

The ELISA responses detected in serum samples from the farm-resident pigs of each group (n = 22), which were vaccinated with FMD vaccines. Blood was collected at 1 week before primary vaccination and 4, 8, 16, 20, and 24 weeks after primary vaccination. Primary and booster vaccination were applied at 8 and 12 weeks of age, respectively. Nine groups were allocated according to the vaccine used: three homologous booster vaccination groups in which A-A, B-B, and C-C regimens were applied, and six heterologous booster vaccination groups in which A-B, A-C, B-A, B-C, C-A, and C-B regimens were applied. The results of the groups primed with O/Manisa + O/3039 + A/Iraq, O/Primorsky+A/Zabaikalsky, and O/Campos + A/Cruzeiro + A/2001 are depicted in (A–C), respectively. Error bars represent the SEMs. The horizontal dashed lines show the cutoff value of the ELISA, 40% percent inhibition (%). * p < 0.05, ** p < 0.01.