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Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses

Khan, SA, Waugh, C, Rawlinson, G, Brumm, J, Nilsson, K, Gerdts, V, Potter, A, Polkinghorne, A, Beagley, K & Timms, P 2014, Vaccine, http://dx.doi.org/10.1016/j.vaccine.2014.08/037

A single-dose Chlamydia vaccine induced significant and long-term cellular and humoral immune responses in six healthy female koalas. The vaccine was based on a three-component adjuvant consisting of polyinosinic-polycytidylic acid (poly I:C), polyphosphazine (PCEP) and a host defence peptide (HDP), combined with the Chlamydia pecorum recombinant chlamydial major outer membrane protein (rMOMP) antigen. Koalas immunised with the vaccine exhibited strong mucosal antibody and C. pecorum-specific neutralising antibody responses in the plasma and at mucosal sites. The vaccine also caused the proliferation of lymphocytes responding specifically to both whole chlamydial elementary bodies and C. pecorum rMOMP protein.

  For six healthy female koalas at Lone Pine Koala Sanctuary, the vaccine’s neutralisation effect in plasma and mucosal secretions at various stages after immunisation was determined. To be effective against chlamydial infections in koalas, a vaccine must induce a strong Th1 immune response at the site of the infection, as well as the creation of neutralising antibodies at mucosal urogenital and ocular sites. The adjuvant components of the vaccine trialled here were selected to fulfil these criteria. Poly I:C has previously been used to induce a Th1 immune response whereby proinflammatory cytokines attack the intracellular pathogenic bacteria, while HDPs are not only antimicrobial but also have an immunomodulatory function in preventing and clearing infection. Polyphosphazines such as PCEP bring myeloid and lymphoid blood cells to the injection site and to draining lymph nodes, further induce proinflammatory cytokines, and can generate strong mucosal antibody responses. In combination, these three adjuvant components induced a significant immune response against chlamydial infection over a period of 54 weeks.

  Chlamydial infections are one of the greatest threats to the survival of koalas in the wild and, therefore, the development of an effective vaccine to combat this threat is a high research priority. Presently, antibiotics are used to treat infections and trials of a three-dose vaccine regimen have shown promising results in preventing the disease. These current measures are limited, however, by the asymptomatic nature of some chlamydial infections and low success rate of antibiotics, and by the impracticality of coordinating multiple immunisation events for a koala in the wild. Furthermore, the administration of a vaccine can be a stressful and invasive experience for the koala, and hence an ideal vaccine should require only a single dose.

  The results of this study take us one step further toward the development of an effective single-dose vaccine that would present a viable alternative to current interventions. The next step in evaluating the efficacy of this novel vaccine will be to evaluate its outcomes in free-ranging koalas.

 

Summarised by Joanna Horsfall

 

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