Contagious bovine pleuropneumonia: A rationale for the development of a mucosal sub-unit vaccine

Abstract

Contagious bovine pleuropneumonia (CBPP) remains a major cattle disease in Africa with serious socio-economic consequences. Its eradication requires the development of improved vaccines. Knowledge on this disease and its causing agent, Mycoplasma mycoides subsp. mycoides biotype Small Colony (MmmSC), has been progressing significantly in the last years, opening new areas for vaccine design. Advances were achieved in the understanding of the protective immune responses to MmmSC infection and immunopathological mechanisms allowing the pathogen to escape the host immune response. Based on sequencing and genomic studies, some virulence factors and metabolic pathways were unraveled leading to the identification of potential MmmSC vaccine candidates. Based on these findings, this review presents a scientific strategy to design multi-component sub-unit vaccines for mucosal delivery as the most promising approach for efficient long-term protective vaccines to prevent CBPP.

Analysis of immune responses to recombinant proteins from strains of Mycoplasma mycoides subsp. mycoides, the causative agent of contagious bovine pleuropneumonia

“…In the latter case, stimulation of purified lymph node lymphocytes from cattle challenged with Mmm was observed after stimulation with LppA (Dedieu et al, 2010). In most cases however, proliferative responses were measured in draining lymph nodes obtained from Mmm-challenged animals and stimulated with Mmm (Dedieu et al, 2005(Dedieu et al, , 2006Dedieu-Engelmann, 2008;Jores et al, 2008;Totte et al, 2008). Our study design did not include proliferation assays on draining lymph node lymphocytes since challenge of cattle with Mmm in Canada is not allowed from a regulatory perspective.…”

“…It has been postulated that for a vaccine to be effective against CBPP, it must also be able to elicit cell-mediated immune responses such as proliferation of CD4+ T-cells in response to the recall antigens (Dedieu et al, 2005(Dedieu et al, , 2006Dedieu-Engelmann, 2008;Jores et al, 2008;Totte et al, 2008). Thus, blastogenesis of PBMC was also measured in all the groups however none of the recombinant antigens were able to elicit recall responses (Suppl.…”

“…These vaccines provide moderate protection, are not very stable and require annual revaccination (Dedieu-Engelmann, 2008). The use of recombinant proteins in a vaccine formulation could make these vaccines cheaper to produce and preserve and more stable (Dedieu-Engelmann, 2008;March, 2004;March et al, 2002;Mbulu et al, 2004;Mulongo et al, 2013). Conventional identification of vaccine targets was based on the ability of sera from immune animals to recognize antigens that can be purified and formulated into vaccines.…”

Recombinant Surface Proteomics as a Tool to Analyze Humoral Immune Responses in Bovines Infected by Mycoplasma mycoides Subsp. mycoides Small Colony Type

“…The use of chemotherapy in CBPP control is a debated subject, has long been discouraged, and is even illegal in some countries (1), mainly because of the risk of creating silent carriers of the disease (8). However, new antibiotics have shown positive effects (9), but extensive vaccinations are still considered the preferred option for prevention and control of CBPP in Africa (2,10,11). The vaccines currently in use are based on live attenuated M. mycoides SC strains and have several disadvantages such as short term immunity (12), poor protection as indicated in recent trials (4,13), and even pathogenicity (13,14).…”

Protein-Specific Analysis of Humoral Immune Responses in a Clinical Trial for Vaccines against Contagious Bovine Pleuropneumonia

“…The polysaccharide antigen has only been evaluated in mice, and the LppQ immunizations seemed to exacerbate the CBPP symptoms in cattle. Subunit vaccines are still desired for CBPP prevention (10), and possible components can be proteins of known pathogenicity mechanisms, as recently reviewed (30). Among these are the well-characterized lipoproteins LppA (6), LppB (38), LppC (31), and LppQ (1) and the variable surface protein Vmm (29).…”