An antigen panel to assess the regional relevance of foot and mouth disease vaccines

Abstract

Despite widespread use of inactivated vaccines to control foot-and-mouth disease (FMD), there is no systematic approach to demonstrate the regional relevance of these products against the specific serotypes and strains that circulate in endemic countries in Africa and Asia. Failure to adopt independent testing of FMD vaccines has contributed to poor trust in their quality and a lack of investment in vaccination programmes. Therefore, a reference antigen panel representing four serotypes, tailored for East Africa, has been established and used to measure FMDV-specific antibody responses in cattle after administration of FMD vaccines commercially available in the region. This revealed inconsistencies and gaps in cross-neutralisation responses that are evident for some vaccines even after giving booster doses. It is concluded that the East Africa reference antigen panel can be used to evaluate FMD vaccine potency and drive up vaccine quality. Further panels could be developed and deployed for other endemic regions.

Fig. 1. Flow chart summarising the procedure for the selection of the East Africa reference antigen panel of viruses.

Use of phylogeny and antigenic typing with monoclonal and polyclonal antibodies to select viruses representative of the diversity of FMDVs found in East Africa.

Fig. 2. Phylogenetic representation (based on VP1 coding sequences) of FMDV lineages circulating in East Africa.

Candidate reference antigens are indicated by the coloured dots, from which the 16 reference antigens (highlighted by circles and numbered as in Table 1) in the East Africa panel were selected. The reconstructed trees also include sequences for FMD viruses isolated from other African regions, which were excluded from the selection process.

Fig. 3. Antigenic relationships revealed by Mab typing.

The order of both row and column items is defined by modular leaf ordering methods and based on the smallest average distance of the estimated subtrees. The percentage of reactivity is normalised and expressed on a scale from 0 to 100. The panel viruses are highlighted with delineated reactivity pattern borders. For each serotype the four highlighted viruses are those selected for the final panel. A Results for serotype O viruses, typed with Mabs raised against different O strains (7E1 and 4B7 were raised against O/Italy/93, whilst the others were raised against O/Switzerland/1965, O/UKG/2001 or O Manisa as indicated in the Mab name). B Results for serotype A viruses, typed with Mabs raised against different A strains (as indicated in the Mab name). C Results for serotype SAT 1 viruses, typed with Mabs raised against SAT 1/BOT 1/68. D Results for serotype SAT 2 viruses, typed with Mabs raised against SAT 2/ZIM/5/81.

Fig. 4. Antigenic relationships revealed by neutralisation tests.

The antibody titres are expressed in log₁₀, with the test viruses and their associated topotypes listed on the right-hand vertical axis. The different sera are on the x axis and named and coloured according to the vaccine strain against which the antiserum was raised. Duplicated sera are from different cattle. The order of both row and column items is defined by modular leaf ordering methods and based on the smallest average distance of the estimated subtrees. The panel viruses are highlighted with delineated reactivity pattern borders. A serotype O; B serotype A; C serotype SAT 1; D serotype SAT 2.

Fig. 5. VNT titres elicited by 13 vaccine batches against the 16 reference panel viruses.

Error bars show the standard deviation of mean values. Dotted line at log₁₀ 1.5 represents the central threshold for expectancy of 75% cross-protection. The lowest serum dilution was 0.9, and titres below this have been attributed the value 0.6. The “b” suffix to the batch number indicates where a booster vaccination was given. Batches 11 and 12 did not contain antigens of serotypes SAT 1, and Batch 13 did not contain O/A antigens. Batch 9–10 results are faintly coloured to indicate results of doubtful (batch 9) or rejected (batch 10) validity due to concerns over the pre-vaccination immunological status of cattle (see text).

Fig. 6. Possible pipeline for heterologous serology use in FMD vaccine QC.

Circumstances where more or less rigorous approaches (full or limited) could be used for serological testing of vaccine potency using all or part of a reference antigen panel.