Maternally Derived Antibodies to Foot-and-Mouth Disease Virus Modulate the Antigenic Specificity of Humoral Responses in Vaccinated Cattle

Abstract

Vaccination is widely used to control foot-and-mouth disease (FMD), but maternal antibodies may interfere with the response to vaccination in calves. This study, conducted on a regularly vaccinated Malaysian dairy farm, aimed to optimise the vaccination regime by measuring the in vitro neutralising virus antibody responses of 51 calves before and after vaccination with a one or two dose vaccination regime starting at 2-7 months old. The presence of maternal antibodies was associated with poor post-vaccination antibody responses after a single dose of vaccine in calves less than 6 months old. However, a second dose of vaccine given three weeks later, improved the antibody responses in all ages of calves. This confirms the view that in regularly vaccinated farms, some combination of delay and revaccination is needed to achieve effective immunization of calves. Sera from cows and pre-vaccinated calves neutralised homologous serotype A vaccine virus more strongly than a heterologous serotype A field virus, but this pattern was reversed in some calves after vaccination. The strength of heterologous responses in calves 49 days after first vaccination correlated to the amount of transferred maternal antibody, suggesting that pre-existing antibodies could have modulated the specificity of these active antibody responses. If confirmed, such an effect by pre-existing antibodies could have wider implications for broadening the coverage of FMD vaccine responses.

Keywords: FMD vaccination; antigen specificity; epitope masking; maternal antibody.

Figure 1

Homologous and heterologous FMDV-serotype A-specific neutralisation antibody titres for cows (dams). Reciprocal neutralisation antibody titres (log₁₀) of individual adult cows against homologous (A/May-97, blue) and heterologous (A/MAY/2/2011, red) viruses. Dotted lines provide thresholds predicted for 95% and 50% homologous protection (blue, ref. [23]) and for upper and lower predicted thresholds of 75% heterologous protection (red, ref. [24]).

Figure 2

Decay of maternally derived neutralisation titres in unvaccinated calves. Reciprocal log₁₀ titres measured against the homologous (A/May-97, blue) vaccine virus and the heterologous (A/MAY/2/2011, red) field virus. Dots indicate actual titres at given calf ages, with predicted decay line and associated uncertainty determined by linear regression. The horizontal dotted black lines represent thresholds for expectancy of protection for serotype A. This is set at 1.4 log₁₀ for homologous titres equating to 50% protection [23] and at 1.2 log₁₀ for heterologous titres, which is the lower threshold for 75% cross-protection [24].

Figure 3

Neutralising antibodies in calves before and after vaccination. All calves were vaccinated for the first time at day 0 and half were revaccinated (boosted) at day 21. Solid points represent homologous (A/May/97) titres, whilst open points represent heterologous (A/MAY/2/2011) titres. Circles represent unboosted calves (top four rows) and triangles represent calves given a booster vaccination at 21 dpv (bottom four rows). The black dashed line indicates the time of the booster vaccination. Samples were taken on the day of first vaccination and then at 21 and 49 days afterwards. Age of calves: 2 months, dark blue; 3 months, red; 4 months, yellow; 5 months, purple; 6 months green; 7 months, light blue.

Figure 4

Effect of pre-vaccination homologous calf titres on post-vaccination antibody responses. Left hand panels show homologous titre changes from pre-vaccination values at given times, plotted against homologous pre-vaccination titres. Right hand panels show heterologous minus homologous log titres at given times, plotted against pre-vaccination homologous log titres. Age of animals (2–7 months) at vaccination according to colour coding in key, with circles representing unboosted calves and triangles representing calves given a booster vaccination at 21 dpv. In each panel, ρ gives Spearman’s rank correlation coefficient between the change in homologous titre or the difference in homologous and heterologous titres and the pre-vaccination titre.