Depletion of CD8+ T cells from vaccinated goats does not affect protection from challenge with wild-type peste des petits ruminants virus.

Peste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East and Asia. The disease is caused by peste des petits ruminants virus (PPRV); cell culture-attenuated strains of PPRV have been shown, both experimentally and by extensive use in the field, to be effective vaccines and are widely used. We have previously demonstrated that these vaccines elicit both serological (PPRV-specific antibody) and cell-based (PPRV-specific CD4+ and CD8+ T cells) immune responses. However, it is not known which of these responses are required for protection from PPRV, information that would be useful in the evaluation of new vaccines that are being developed to provide the capability to differentiate infected and vaccinated animals (DIVA capability). To begin to address this issue, we have used a complement-fixing monoclonal antibody recognizing caprine CD8 to deplete >99.9% of circulating CD8+ T cells from vaccinated goats. Animals were then infected with wild-type PPRV. Despite the absence of the CD8+ T-cell component of the vaccine-induced immune response, the vaccinated animals were almost fully protected, showing no pyrexia or viraemia, and almost no clinical signs. These data suggest that a virus-specific CD8+ T-cell response is not critical for protection against PPRV and that virus-specific antibody and/or CD4+ T cells are the main mediators of protection. We have also shown that the leucopenia caused by infection with wild-type PPRV affects all major classes of circulating leucocytes.

Comparison of the Immunogenicities and Cross-Lineage Efficacies of Live Attenuated Peste des Petits Ruminants Virus Vaccines PPRV/Nigeria/75/1 and PPRV/Sungri/96.

Peste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East, and Asia. Several effective vaccines exist for the disease, based on attenuated strains of the virus (PPRV) that causes PPR. While the efficacy of these vaccines has been established by use in the field, the nature of the protective immune response has not been determined. In addition, while the vaccine derived from PPRV/Nigeria/75/1 (N75) is used in many countries, those developed in India have never been tested for their efficacy outside that country. We have studied the immune response in goats to vaccination with either N75 or the main Indian vaccine, which is based on isolate PPRV/India/Sungri/96 (S96). In addition, we compared the ability of these two vaccines, in parallel, to protect animals against challenge with pathogenic viruses from the four known genetic lineages of PPRV, representing viruses from different parts of Africa, as well as Asia. These studies showed that, while N75 elicited a stronger antibody response than S96, as measured by both enzyme-linked immunosorbent assay and virus neutralization, S96 resulted in more pronounced cellular immune responses, as measured by virus antigen-induced proliferation and interferon gamma production. While both vaccines induced comparable numbers of PPRV-specific CD8+ T cells, S96 induced a higher number of CD4+ T cells specifically responding to virus. Despite these quantitative and qualitative differences in the immune responses following vaccination, both vaccines gave complete clinical protection against challenge with all four lineages of PPRV.IMPORTANCE Despite the widespread use of live attenuated PPRV vaccines, this is the first systematic analysis of the immune response elicited in small ruminants. These data will help in the establishment of the immunological determinants of protection, an important step in the development of new vaccines, especially DIVA vaccines using alternative vaccination vectors. This study is also the first controlled test of the ability of the two major vaccines used against virulent PPRV strains from all genetic lineages of the virus, showing conclusively the complete cross-protective ability of these vaccines.

Predicting the Ability of Preclinical Diagnosis To Improve Control of Farm-to-Farm Foot-and-Mouth Disease Transmission in Cattle.

Foot-and-mouth disease (FMD) can cause large disruptive epidemics in livestock. Current eradication measures rely on the rapid clinical detection and removal of infected herds. Here, we evaluated the potential for preclinical diagnosis during reactive surveillance to reduce the risk of between-farm transmission. We used data from transmission experiments in cattle where both samples from individual animals, such as blood, probang samples, and saliva and nasal swabs, and herd-level samples, such as air samples, were taken daily during the course of infection. The sensitivity of each of these sample types for the detection of infected cattle during different phases of the early infection period was quantified. The results were incorporated into a mathematical model for FMD, in a cattle herd, to evaluate the impact of the early detection and culling of an infected herd on the infectious output. The latter was expressed as the between-herd reproduction ratio, Rh , where an effective surveillance approach would lead to a reduction in the Rh value to <1. Applying weekly surveillance, clinical inspection alone was found to be ineffective at blocking transmission. This was in contrast to the impact of weekly random sampling (i.e., using saliva swabs) of at least 10 animals per farm or daily air sampling (housed cattle), both of which were shown to reduce the Rh to <1. In conclusion, preclinical detection during outbreaks has the potential to allow earlier culling of infected herds and thereby reduce transmission and aid the control of epidemics.

Protection of Cattle against Rinderpest by Vaccination with Wild-Type but Not Attenuated Strains of Peste des Petits Ruminants Virus.

UNLABELLED: Although rinderpest virus (RPV) has been eradicated in the wild, efforts are still continuing to restrict the extent to which live virus is distributed in facilities around the world and to prepare for any reappearance of the disease, whether through deliberate or accidental release. In an effort to find an alternative vaccine which could be used in place of the traditional live attenuated RPV strains, we have determined whether cattle can be protected from rinderpest by inoculation with vaccine strains of the related morbillivirus, peste des petits ruminants virus (PPRV). Cattle were vaccinated with wild-type PPRV or either of two established PPRV vaccine strains, Nigeria/75/1 or Sungri/96. All animals developed antibody and T cell immune responses to the inoculated PPRV. However, only the animals given wild-type PPRV were protected from RPV challenge. Animals given PPRV/Sungri/96 were only partially protected, and animals given PPRV/Nigeria/75/1 showed no protection against RPV challenge. While sera from animals vaccinated with the vaccine strain of RPV showed cross-neutralizing ability against PPRV, none of the sera from animals vaccinated with any strain of PPRV was able to neutralize RPV although sera from animals inoculated with wild-type PPRV were able to neutralize RPV-pseudotyped vesicular stomatitis virus. IMPORTANCE: Rinderpest virus has been eradicated, and it is only the second virus for which this is so. Significant efforts are still required to ensure preparedness for a possible escape of RPV from a laboratory or its deliberate release. Since RPV vaccine protects sheep and goats from PPRV, it is important to determine if the reverse is true as this would provide a non-RPV vaccine for dealing with suspected RPV outbreaks. This is probably the last in vivo study with live RPV that will be approved.

Determination of the minimum fully protective dose of adenovirus-based DIVA vaccine against peste des petits ruminants virus challenge in East African goats.

Peste des petits ruminants virus (PPRV) causes an economically important disease of sheep and goats, primarily in developing countries. It is becoming the object of intensive international control efforts. Current vaccines do not allow vaccinated and infected animals to be distinguished (no DIVA capability). We have previously shown that recombinant, replication-defective, adenovirus expressing the PPRV H glycoprotein (AdH) gives full protection against wild type PPRV challenge. We have now tested lower doses of the vaccine, as well as AdH in combination with a similar construct expressing the PPRV F glycoprotein (AdF). We show here that, in a local breed of goat in a country where PPR disease is common (Kenya), as little as 10(7) pfu of AdH gives significant protection against PPRV challenge, while a vaccine consisting of 10(8) pfu of each of AdH and AdF gives apparently sterile protection. These findings underline the utility of these constructs as DIVA vaccines for use in PPR control.