CONTAGIOUS BOVINE PLEUROPNEUMONIA

Contagious bovine pleuropneumonia vaccines

Contagious bovine pleuropneumonia (CBPP) vaccines have often been the subject of debate, possibly more so than any other type of bacterial vaccine. These debates became more pronounced when the T₁SR strain of vaccine did not seem to induce sufficient protection after the reintroduction of CBPP into Botswana (Amanfu et al., 1998) and East Africa (Masiga, Domenech and Windsor, 1996).

The difficulty with the use of CBPP vaccines is that two different issues are sometimes confused with each other: the efficacy of the vaccine itself, and the efficient conduct of a vaccination campaign. The first issue can be assessed in controlled experiments provided that all the parameters are clearly identified and analysed. The second is far more difficult, and therefore also more controversial, because the efficiency of a vaccination campaign depends not only on the intrinsic quality of the vaccine itself but also on the strategy and logistics for implementation of the vaccinations.

Therefore, the success of a vaccination campaign depends on careful planning. The campaign must be based on accurate scientific data concerning the vaccine itself and the epidemiology of the disease in order to define a strategy that fits the defined objectives. It must also include careful planning of the logistics for implementing that strategy, and must take the “human factor” into account by ensuring that the cattle owners who are beneficiaries of the vaccinations are collectively well aware of the strategy and agree with its aims and methods. The possibility of post-vaccinal reactions following the application of CBPP vaccine must be explained to cattle owners, or they may refuse subsequent vaccination campaigns.

Concerning the CBPP vaccines themselves, questions about the efficacy of the T₁SR vaccine were raised in the mid-1980s, when a vaccination campaign in Botswana failed to prevent the spread of the disease. As this type of vaccine was thought to be efficient (Provost et al., 1987) and there did not seem to be a flaw in the vaccination strategy, it was concluded that there was something wrong with the vaccine strain itself. Consequently, FAO advocated the use of vaccine strain T₁44 and a grand parental stock produced by the Pan-African Veterinary Vaccine Centre, which could be distributed to CBPP vaccine producers. It was believed that the apparent lack of protection from T₁SR might have been the result of a laboratory error in the manipulation of the strain, leading to the misidentification of what was actually another vaccinal strain, KH3J-SR. At that time, there was no laboratory technique for the specific characterization of the vaccine strain. However, since then, a specific polymerase chain reaction (PCR) test has been developed. This PCR test has demonstrated that there was no misidentification and that the vaccine strain used in Botswana really was T₁SR (Lorenzon et al., 2000). Another possible explanation for the lack of potency of the CBPP vaccines could be that a genetic drift occurs during multiple passages in vitro or cloning procedures, resulting in the selection of variants that are less immunogenic than the original vaccine seed stock (Rosengarten and Yogev, 1996). However, there is no laboratory technique for determining the potency of a vaccine seed stock.

Producing CBPP vaccine in conformity with the standards of the International Office of Epizootics (OIE) (Lefevre, 2000) is the only way to ensure the potency of successive batches. Lack of protection from a vaccine strain could also be the result of modifications in the pathogenic strains themselves. In fact, T₁ vaccine strains have been used for decades (Sheriff and Piercy, 1952), and pathogenic strains might have evolved in order to escape the immune response triggered by the vaccine. Such an evolution has already been observed in vitro for some mycoplasmas (Le Grand et al., 1996). Previous vaccine efficacy trials were performed in Africa with a pathogenic strain from Australia, the Gladysdale strain (Masiga and Windsor, 1974), under the assumption that Mycoplasma mycoides subsp. mycoides small colony variant (MmmSC) strains were very homogeneous. Since then, it has been shown that there is actually great genetic diversity among the pathogenic strains of MmmSC circulating in Africa (Lorenzon et al., 2003). Such diversity may have been responsible for a lack of protection from the vaccine strain in the Botswana outbreak.

For all these reasons, it was decided to perform a number of vaccine efficacy trials in different regions of Africa, with financing from the European Union (EU) and the French Ministry of Foreign Affairs and supervision from the African Union/Interafrican Bureau for Animal Resources. The trials took place in Cameroon, Kenya and Namibia, where pathogenic strains of various genotypes are circulating. It was decided to test the efficacy of T₁SR and T₁44 strains at the minimum OIE recommended dose. Naive animals were given a single dose as initial vaccination and were challenged by contact exposure three months later with local and recent pathogenic strains of confirmed virulence. In all cases, the protection afforded by circulating such a vaccination protocol was not satisfactory. Protection varied within the range of 30-60 percent, regardless of the vaccine strain used (Yaya et al., 1999). Furthermore, the T₁44 vaccine induced some untoward post-vaccinal reactions, especially in Kenya. Subsequently, a second experiment was designed in Kenya in which vaccinated animals were divided into two groups: one group received a booster vaccination one year after the initial immunization, while the other group did not receive the booster. The challenge experiment was organized three months after the booster injection. In these conditions, the booster vaccination induced protection that exceeded 85 percent, irrespective of the strain used - T₁SR or T₁44 (Wesonga and Thiacourt, 2000). However, a difference between the two vaccine strains was noted in terms of the longevity of protection. The challenge 15 months after the initial vaccination showed that there was no protection left in the T₁SR-vaccinated group. The initial protection rate was maintained for T₁44. These results provided some explanations of what might have occurred in Botswana. It is unlikely that the use of T₁44 instead of T₁SR would have modified the outcome to any great extent, and initial vaccinations may have been more efficient if the vaccine dose had been increased. Such a correlation between protection and vaccine dose has been performed only once and will be re-evaluated in 2003-2004 within the CBPP-Pan-African Programme for the Control of Epizootics (PACE) research programme at the National Veterinary Laboratory in Cameroon. Similarly, greater and more persistent protection might have been obtained by giving a booster dose shortly after the initial dose. Such a protocol is quite common for a number of vaccines, and its efficacy for CBPP vaccines will be tested at the Kenya Agricultural Research Institute.

Clearly, the ideal CBPP vaccine has not yet been developed. The main drawback with T₁SR is that it gives short-term immunity. On the other hand, T₁44 occasionally induces local post-vaccinal reactions, and some authors have noted that it could induce lung lesions in exceptional cases (Huebschle et al., 2002). However, CBPP vaccines do offer some advantages: they are relatively cheap to produce, and the protection rate afforded by multiple vaccinations is satisfactory. Therefore, CBPP vaccines can still play a major role in control programmes, although their use cannot follow a general guideline that could be applied by every country or region. Each veterinary service should consider the peculiarities and CBPP epidemiology of its own country within the regional context in order to design specific guidelines that will be both less expensive and more efficient to implement.

References

Amanfu, W., Masupu, K.V., Adom, E.K., Raborokgwe, M.V. & Bashiruddin, J.B. 1998. An outbreak of contagious bovine pleuropneumonia in Ngamiland district of north-western Botswana. Vet. Rec., 143: 46-48.

Huebschle, O., Lelli, R., Frey J. & Nicholas, R. 2002. Letter to Vet. Rec., 11 May, 615.

Le Grand, D., Solsona, M., Rosengarten, R. & Poumarat, F. 1996. Adaptative surface antigen variation in Mycoplasma bovis to the host immune response. FEMS microbiology letters; 144: 267-275.

Lefevre, P.C. 2000. Contagious bovine pleuropneumonia. In OIE, Manual of standards for diagnostic tests and vaccines, pp. 123-133. Paris, OIE.

Lorenzon, S., Arzul, I., Peyraud, A., Hendrikx, P. & Thiaucourt, F. 2003. Molecular epidemiology of CBPP by multilocus sequence analysis of Mycoplasma mycoides subsp. mycoides SC strains. Vet. Microbiol., accepted.

Lorenzon, S., David, A., Nadew, M., Wesonga, H. & Thiaucourt, F. 2000. Specific PCR identification of the T1 vaccine strains for contagious bovine pleuropneumonia. Mol. Cell Probes, 14: 205-210.

Masiga, W.N. & Windsor, R.S. 1974. The efficacy of T₁ strain broth culture vaccine against contagious bovine pleuropneumonia: the effect of revaccination of cattle 6 months and 1 year after primary vaccination and prolonged exposure. Bull. Epiz. Dis. Afr., 12: 27-31

Masiga, W.N., Domenech, J. & Windsor, R.S. 1996. Manifestation and epidemiology of contagious bovine pleuropneumonia in Africa. Rev. Sci. Tech. Off. Int. Epiz., 15: 1283-1308.

Provost, A., Perreau, P., Breard, A., Le Goff, C., Martel, J.L. & Cottew, G.S. 1987. Contagious bovine pleuropneumonia. Rev. Sci. Tech. Off. Int. Epiz., 6: 625-679.

Rosengarten, R. & Yogev, D. 1996. Variant colony surface antigenic phenotypes within mycoplasma strain populations: implication for species identification and strain standardization. J. Clin. Microbiol., 34: 149-158.

Sheriff, D. & Piercy, S.E. 1952. Experiments with an avianised strain of the organism of contagious bovine pleuropneumonia. Vet. Rec., 64: 615-621.

Wesonga, H.O. & Thiaucourt, F. 2000. Experimental studies on the efficacy of T₁SR and T1/44 vaccine strains of MmmSC against a field isolate causing contagious bovine pleuropneumonia in Kenya: effect of a revaccination. Rev. Elev. Med. Vet. Pays Trop., 53: 313-318.

Yaya, A., Golsia, R., Hamadou, B., Amaro, A. & Thiaucourt, F. 1999. Essai comparatif d'efficacité des deux souches vaccinales T₁ 44 et T₁ SR contre la péripneumonie contagieuse bovine. Rev. Elev. Med. Vet. Pays Trop., 52: 171-179.